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HUMAN EVOLUTIONARY BIOLOGY
Wide-ranging and inclusive, this text provides an invaluable review of an expansive

selection of topics in human evolution, variation, and adaptability for professionals
and students in biological anthropology, evolutionary biology, medical sciences, and
psychology. The chapters are organized around four broad themes, with sections
devoted to phenotypic and genetic variation within and between human populations,
reproductive physiology and behavior, growth and development, and human health
from evolutionary and ecological perspectives. An introductory section provides
readers with the historical, theoretical, and methodological foundations needed to
understand the more complex ideas presented later. Two hundred discussion ques-
tions provide starting points for class debate and assignments to test student
understanding.
Michael P. Muehlenbein is an assistant professor of anthropology at Indiana

University, Bloomington. He holds an MsPH in both tropical medicine and biosta-
tistics from Tulane University, as well as an MPhil and PhD in biological anthropol-
ogy from Yale University. His research interests are focused most recently on
(1) evaluating hormone-mediated immune functions in reference to evolutionary
and life history theories, and (2) investigating potential zoonotic and anthropozoo-
notic pathogen transmission associated with primate-based ecotourism. He has
received teaching awards for his graduate and undergraduate courses on human
biological variation, behavioral endocrinology, evolutionary medicine, and global
health. In addition to running an endocrinology and infectious disease laboratory
in Indiana, he presently conducts fieldwork in the United States, Malaysia, Dominica,
and the Dominican Republic.
HUMAN EVOLUTIONARY
BIOLOGY
Edited by
MICHAEL P. MUEHLENBEIN
Indiana University, Bloomington
CAMBRIDGE UNIVERSITY PRESS
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Cambridge University Press

The Edinburgh Building, Cambridge CB2 8RU, UK
Published in the United States of America by Cambridge University Press, New York
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# Cambridge University Press 2010
This publication is in copyright. Subject to statutory exception

and to the provisions of relevant collective licensing agreements,
no reproduction of any part may take place without
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First published 2010
Printed in the United Kingdom at the University Press, Cambridge
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ISBN 978-0-521-70510-3 Paperback
Cambridge University Press has no responsibility for the persistence

or accuracy of URLs for external or third-party internet websites
referred to in this publication, and does not guarantee that any
content on such websites is, or will remain, accurate or appropriate.
Contents
List of contributors page vii 11 Human Adaptation to High Altitude 170

Preface xi Tom D. Brutsaert
12 Skin Coloration 192

Part I Theory and Methods 1 Nina G. Jablonski
1 Evolutionary Theory 3 13 Classic Markers of Human Variation 214

Douglas J. Futuyma Robert J. Meier
2 The Study of Human Adaptation 17 14 DNA Markers of Human Variation 238

A. Roberto Frisancho Michael E. Steiper
3 History of the Study of Human Biology 29 15 Ten Facts about Human Variation 265
Michael A. Little Jonathan Marks
4 Genetics in Human Biology 48 16 The Evolution and Endocrinology

Robert J. Meier and Jennifer A. Raff of Human Behavior: a Focus on
Sex Differences and Reproduction 277
5 Demography 74
Peter B. Gray
James Holland Jones
6 History, Methods, and General

Applications of Anthropometry Part III Reproduction 293
in Human Biology 92 17 Human Mate Choice 295
Noël Cameron and Laura L. Jones David P. Schmitt
7 Energy Expenditure and Body 18 Mate Choice, the Major
Composition: History, Methods, Histocompatibility Complex,
and Inter-relationships 113 and Offspring Viability 309
Peter S. W. Davies and Alexia J. Murphy Claus Wedekind and Guillaume Evanno
8 Evolutionary Endocrinology 127 19 Why Women Differ in Ovarian Function:
Richard G. Bribiescas and Genetic Polymorphism, Developmental
Michael P. Muehlenbein
Conditions, and Adult Lifestyle 322
9 Ethical Considerations for Human Grazyna Jasienska
Biology Research 144 20 Pregnancy and Lactation 338
Trudy R. Turner Ivy L. Pike and Lauren A. Milligan
With commentary by Michael P. Muehlenbein
Commentary: a Primer on Human Subjects 21 Male Reproduction: Physiology,
Applications and Informed Consents 150 Behavior, and Ecology 351
Michael P. Muehlenbein Michael P. Muehlenbein and
Richard G. Bribiescas
Part II Phenotypic and Genotypic Variation 155

Part IV Growth and Development 377
10 Body Size and Shape: Climatic and Nutritional
Influences on Human Body Morphology 157 22 Evolution of Human Growth 379
William R. Leonard and Peter T. Katzmarzyk Barry Bogin
v
vi Contents
23 Variation in Human Growth Patterns due to 29 Evolutionary Medicine and the Causes
Environmental Factors 396 of Chronic Disease 502
Stanley J. Ulijaszek Paul W. Ewald
24 Evolutionary Biology of Hormonal Responses 30 Beyond Feast–Famine: Brain Evolution,

to Social Challenges in the Human Child 405 Human Life History, and the Metabolic
Mark V. Flinn Syndrome 518
Christopher W. Kuzawa
25 Human Biology, Energetics,
and the Human Brain 425 31 Human Longevity and Senescence 528
Benjamin C. Campbell Douglas E. Crews and James A. Stewart
26 Embodied Capital and Extra-somatic Wealth 32 Evolutionary Psychiatry: Mental

in Human Evolution and Human History 439 Disorders and Behavioral Evolution 551
Jane B. Lancaster and Hillard S. Kaplan Brant Wenegrat
33 Industrial Pollutants and

Part V Health and Disease 457 Human Evolution 566
Lawrence M. Schell
27 Evolutionary Medicine, Immunity,
and Infectious Disease 459 34 Acculturation and Health 581
Michael P. Muehlenbein Thomas W. McDade and Colleen H. Nyberg
28 Complex Chronic Diseases

Index 603
in Evolutionary Perspective 491
S. Boyd Eaton
Contributors
Barry Bogin Paul W. Ewald

Department of Human Sciences Department of Biology
Loughborough University University of Louisville
Loughborough, UK Louisville, KY, USA
Richard G. Bribiescas Mark V. Flinn
Department of Anthropology Department of Anthropology
Yale University, University of Missouri
New Haven, CT, USA Columbia, MO, USA
Tom D. Brutsaert A. Roberto Frisancho
Department of Exercise Science Department of Anthropology
Syracuse University University of Michigan
Syracuse, NY, USA Ann Arbor, MI, USA
Noël Cameron Douglas J. Futuyma
Department of Human Sciences Department of Ecology and Evolution
Centre for Human Development and Ageing State University of New York, Stony Brook
Loughborough University Stony Brook, NY, USA
Loughborough, UK
Peter B. Gray
Benjamin C. Campbell Department of Anthropology and Ethnic
Department of Anthropology Studies
University of Wisconsin University of Nevada, Las Vegas
Milwaukee, WI, USA Las Vegas, NV, USA
Douglas E. Crews Nina G. Jablonski
Department of Anthropology Department of Anthropology
Ohio State University Pennsylvania State University
Columbus, OH, USA University Park, PA, USA
Peter S. W. Davies Grazyna Jasienska
Children’s Nutrition Research Centre Department of Epidemiology and Population
Discipline of Paediatrics and Child Health Studies
The University of Queensland Institute of Public Health
Royal Children’s Hospital Jagiellonian University, Collegium Medicum
Herston, Australia Krakow, Poland
S. Boyd Eaton James Holland Jones

Department of Anthropology Department of Anthropological Sciences
Emory University Stanford University
Atlanta, GA, USA Stanford, CA, USA
Guillaume Evanno Laura L. Jones

Department of Ecology and Evolution Division of Epidemiology and Public Health
University of Lausanne Nottingham City Hospital
Lausanne, Switzerland Nottingham, UK
vii
viii List of contributors
Hillard S. Kaplan Royal Children’s Hospital

Department of Anthropology Herston, Australia
University of New Mexico
Colleen H. Nyberg
Albuquerque, NM, USA
Department of Anthropology
Peter T. Katzmarzyk University of Massachusetts Boston
Pennington Biomedical Research Center Boston, MA, USA
Baton Rouge, LA, USA
Ivy L. Pike
Christopher W. Kuzawa Department of Anthropology
Department of Anthropology University of Arizona
Northwestern University Tucson, AZ, USA
Evanston, IL, USA
Jennifer A. Raff
Jane B. Lancaster Department of Anthropology
Department of Anthropology University of Utah
University of New Mexico Salt Lake City, UT, USA
Albuquerque, NM, USA
Lawrence M. Schell
William R. Leonard Department of Anthropology
Department of Anthropology State University of New York, Albany
Northwestern University Albany, NY, USA
Evanston, IL, USA
David P. Schmitt
Michael A. Little Department of Psychology
Department of Anthropology Bradley University
State University of New York, Binghamton Peoria, IL, USA
Binghamton, NY, USA
Michael E. Steiper
Jonathan Marks Department of Anthropology
Department of Anthropology Hunter College
University of North Carolina, Charlotte New York, NY, USA
Charlotte, NC, USA
James A. Stewart
Thomas W. McDade Department of Social and Behavioral Sciences
Department of Anthropology Columbus State Community College
Northwestern University Columbus, OH, USA
Evanston, IL, USA
Trudy R. Turner
Robert J. Meier Department of Anthropology
Department of Anthropology University of Wisconsin-Milwaukee
Indiana University Milwaukee, WI, USA
Bloomington, IN, USA
Stanley J. Ulijaszek
Lauren A. Milligan Institute of Social and Cultural Anthropology
Department of Anthropology University of Oxford
University of California, Santa Cruz Oxford, UK
Santa Cruz, CA, USA
Claus Wedekind
Michael P. Muehlenbein Department of Ecology and Evolution
Department of Anthropology University of Lausanne
Indiana University Lausanne, Switzerland
Bloomington, IN, USA
Brant Wenegrat
Alexia J. Murphy Department of Psychiatry and Behavioral
Children’s Nutrition Research Centre Sciences
Discipline of Paediatrics and Child Health Stanford University
The University of Queensland Palo Alto, CA, USA
Preface
In review of a different text, Moses Hadas (1900–1966) reviews of basic evolutionary biology, molecular bio-
remarked that “this book fills a much-needed gap.” logy, biological anthropology, behavioral ecology, and
Unlike the text he was referring to, the topic of human statistics. We have, however, tried to produce a text
evolutionary biology deserves no such gap in our readable to a wide audience and organized in an intui-
understanding. To identify one’s place in nature and tive fashion. Part I of the book begins where it should,
to appreciate how human evolution has been guided by with basic and detailed reviews of theory, history, and
the same evolutionary principles that guide other methods in human evolutionary biology. This includes
organisms is humbling and necessary. We are products introductions to evolutionary theory, human adap-
of evolution, and this is reflected throughout our bio- tability, genetics, demography, evolutionary endocri-
logy and behaviors. nology, anthropometry, and nutrition/energetics, as
The purpose of our text is to provide thorough and well as the history of the study of human biology. We
modern reviews of a wide range of pertinent aspects of even introduce readers to some of the ethical consider-
human evolutionary biology and contemporary human ations for human biology research. Clearly the purpose
biological variation. The history of research on human of Part I is to provide readers with a basic foundation
biological variation is a long one, and includes studies in theory and methodology that can be used as a basis
on general human adaptability, variations in growth for understanding some of the more complex problems
patterns, body sizes and shapes, genetic diversity, and presented by authors throughout the remainder of the
race concepts. More recently, the study of human bio- volume.
logy has included analyses of reproductive physiology Part II of the book focuses on phenotypic and geno-
and behavior within evolutionary and ecological typic variation. This has been the bread and butter of
frameworks. Other advancements include the science research on contemporary human biological variation.
of evolutionary medicine, in which evolutionary Body size and shape, skin color, and adaptations to
research on health and disease is used to elucidate high altitude are all revisited. Chapters 13 and 14 pro-
medical research and practices. vide detailed accounts of classic (e.g., serological, etc.)
The text before you is different from most others. and DNA markers of human variation, and Chapter 15
Unlike traditional texts on evolutionary biology, our importantly addresses the “race concept,” a long-held
book focuses specifically on humans and the applica- discussion in physical and cultural anthropology.
tion of evolutionary theories on understanding modern A chapter on human behavioral endocrinology logic-
human variation and adaptability. Unlike traditional ally bridges our section on phenotypic/genotypic vari-
texts on human biology, our book does not include ation with the following Part III: reproduction. This
detailed descriptions of all human physiological and section begins with more discussion on human beha-
anatomical systems. You will also not find detailed viors, specifically mate choice. Female reproductive
accounts of the history of human evolution, where we ecology/physiology is addressed in Chapters 19 and
came from and how we are related to other species. 20, and male reproductive ecology/physiology in
What you will find are historical perspectives on the Chapter 21. Unfortunately, we were unable to provide
study of human evolutionary biology, detailed reviews at this time a chapter on female reproductive senes-
of modern methods for studying human evolutionary cence (i.e., the menopause).
biology, descriptions of fundamental research on geno- As Part IV focuses on growth and development, it
typic and phenotypic variation within and between contains discussions on the evolution of, and variation
contemporary human populations, comprehensive in, rates and patterns of somatic growth. This includes
discussions on human reproductive physiology and classic and modern ideas on the sensitivity of human
behavior as well as evolutionary medicine. development to environmental factors like nutrition,
It is not possible to produce one single inclusive disease, and even social challenges. Chapter 26 shows
text on such a diverse topic. Supplemental materials us how human life histories, cognition, and body/brain
to our book would include, among others, detailed development are intimately intertwined. Its discussion
ix
x Preface
on human longevity also serves as a logical transition contents of different chapters to their classmates. It is
to our final section of the book. Part V focuses on never too early to learn how to give an effective presen-
various aspects of human health from evolutionary tation. Readers are also encouraged to utilize the
and ecological perspectives. This includes basic dis- questions listed at the end of each chapter to facilitate
cussions of immunity and infectious diseases, the discussion. Identifying and stimulating future direc-
evolution of chronic diseases (including the meta- tions of research should be the primary goal.
bolic syndrome and mental disorders), the infectious Lastly, credit must be given where credit is due.
causes of some chronic diseases, and human senes- Acknowledgements belong to Dr. Dominic Lewis and
cence. We conclude the section and book with discus- others at Cambridge University Press for being brave
sions on some of the cultural determinants of health enough to tackle this project. The friends, families, and
that have and will continue to be influential on human colleagues who assisted each contributing author
evolution. are too numerous to list, but all deserve recognition.
We have intended this text to be used as a general We do not do this by ourselves or for ourselves.
reference for professional scholars as well as graduate/
postgraduate students and advanced undergraduates . . . And we must acknowledge, as it seems to me, that man
in evolutionary biology, biological anthropology, and with all his noble qualities, with sympathy which feels for
the most debased, with benevolence which extends not only
other academic programs. The ultimate goal is to
to other men but to the humblest living creature, with his
forward research on human evolutionary biology by
god-like intellect which has penetrated into the movements
identifying gaps in our understandings of this inclusive and constitution of the solar system – with all these exalted
discipline. Admittedly, it may be difficult to cover all powers – Man still bears in his bodily frame the indelible
chapters of this book in a single semester in a class- stamp of his lowly origin.
room setting. In this case, instructors may choose to
focus only on certain sections. Alternatively, instruct- Charles Darwin (1809–1882), The Descent of Man and
ors may choose to have different students present the Selection in Relation to Sex (1871), p. 405.
Part I
Theory and Methods
“The natural phenomena of the evolutionary history of

man claim an entirely peculiar place in the wide range
of the scientific study of nature. There is surely no
subject of scientific investigation touching man more
closely, or in the knowledge of which he is more deeply
concerned, than the human organism itself; and of all
the various branches of the science of man, or
anthropology, the history of his natural evolution
should excite his highest interest.”
Ernst Haeckel (1834–1919), The Evolution
of Man (1892), p. 2
1
1 Evolutionary Theory
Douglas J. Futuyma
Our contemporary understanding of evolutionary material, and even changes in ploidy. Many mutations
processes builds on theory developed during the have no effect on phenotype or fitness (are selectively
“Evolutionary Synthesis” of the 1930s and 1940s, when neutral), such as synonymous mutations in protein-
Darwin’s ideas, especially on natural selection, were coding regions, which do not alter amino acid sequence,
joined with Mendelian genetics. Since, then, of course, and mutations that occur in pseudogenes and other
our understanding of evolution has been greatly apparently nonfunctional regions. There exists greater
advanced by the discoveries in molecular genetics, as potential for fitness effects of nonsynonymous muta-
well as by continuing elaboration of the “neo-Darwinian” tions in coding regions, or of mutations in regulatory
theory that issued from the Evolutionary Synthesis sequences. The rate of mutation (usually on the order
(Futuyma, 1998, 2005). of 10–9 per base pair per gamete) is usually too low
A capsule summary of contemporary theory, to be to be a significant factor in driving allele frequency
followed by more detailed explication, is as follows. change within a population, but it can determine the
Elementary evolutionary change consists of changes rate of DNA sequence divergence in the long term, and
in the genetic constitution of a population of organ- can influence the equilibrium level of standing genetic
isms, or in an ensemble of populations of a species. variation. Considerable contemporary research con-
These genetic changes may be reflected in change of cerns whether or not rates and directions of pheno-
the population mean or variance of phenotypic charac- typic evolution are often constrained by the supply of
teristics. Any change requires that genetic variation suitable mutations (Houle, 1998; Blows and Hoffmann,
originate by mutation of DNA sequences, and/or by 2005). Mutation is a random process, in the sense
recombination. The minimal evolutionary process is that the probability of occurrence of a particular muta-
an increase in the frequency of a mutation, or a set of tion is not affected by environmental circumstances
mutations, within a population, and the corresponding which would make it advantageous. That is, there is
decrease in frequency of previously common alleles. no known mechanism by which the mutational process
Such frequency changes are the consequence of random can be directed by the environment in advantageous
genetic drift (leading to occasional fixation of nearly directions.
neutral genetic variants) or of diverse forms of natural
selection. Successive such changes in one or more
characteristics cumulate over time, yielding potentially VARIATION WITHIN POPULATIONS
indefinite divergence of a lineage from the ancestral
state. Different populations of a species retain similar- Based on studies of many species, it appears that most
ity due to gene flow and perhaps uniform selection, but populations carry substantial sequence variation in
can diverge due to differences in mutation, drift, and/or many gene loci, and that there exists some heritable
selection. Some of the consequent genetic differences variation in many or most “quantitative” phenotypic
can generate biological barriers to gene exchange traits (continuous traits such as size, as well as the
between populations, resulting in the formation of number of highly repeated unit characters, such as
different biological species. hairs or scales). Presence of two or more fairly common
alleles or genotypes within a population is referred to as
polymorphism. The level of variation is enhanced by
THE ORIGIN OF VARIATION mutation, recombination (often but not always), gene
flow from other, genetically differentiated, populations,
Mutational changes in DNA sequences are of many and some forms of natural selection (e.g., frequency-
kinds, ranging from single base-pair alterations to dependent selection, below). It is eroded by genetic
insertions, deletions, and rearrangements of genetic drift and by most forms of natural selection (including
Human Evolutionary Biology, ed. Michael P. Muehlenbein. Published by Cambridge University Press. # Cambridge University Press 2010.
3
4 Douglas J. Futuyma
directional and stabilizing selection on quantitative termed the heritability (in the narrow sense), defined
traits). The analysis of genetic variation is based on more narrowly than the “broad sense heritability”
the frequencies of the alleles and genotypes at individ- VG/VP. Because VA is a function of allele frequencies,
ual genetic loci (for an introduction to population and VP includes the environmental variance VE, an
genetics, see Hartl and Clark, 1997) For sexually estimate of the heritability of a trait is valid only for
reproducing populations, the Hardy–Weinberg (H-W) the particular population and the particular environ-
theorem states that the frequency of each allele (pi ment in which it was estimated, since other popula-
for allele i) will remain constant from generation to tions might differ in both these respects. Although
generation unless perturbed by mutation, gene flow, many or most characters are genetically variable,
sampling error (genetic drift), or selection, and that we do not know what fraction of this variation can
the frequencies of the several genotypes will likewise contribute to evolution by natural selection, since it is
remain constant, at values given by the binomial the- possible that a considerable portion of the variation
orem (pi2 for homozygote AiAi, and 2pipj for hetero- may be deleterious under most circumstances.
zygote AiAj), if mating occurs at random. A single The “mapping,” or relationship, between a pheno-
generation of random mating establishes H-W genotypic character state (e.g., body mass) and the environ-
type frequencies at any autosomal locus. Furthermore, ment (e.g., caloric intake) is a genotype’ norm of
alleles at two or more polymorphic loci will become reaction. Genotypes may differ in their norms of reac-
randomized with respect to each other (a state of tion; for example, some people may gain more weight
linkage equilibrium) due to recombination. These prin- on a given diet than others. Such differences give rise to
ciples have important consequences; for example, at a genotype X environment interaction, expressed at the
H-W equilibrium, a rare allele exists mostly in hetero- population level by the variance component VGXE. The
zygous state, and so is concealed if it is recessive. In “mapping” between genotypes and phenotypes, even
fact, rare, deleterious recessive alleles exist at a great within a constant environment, often depends on devel-
many loci in populations of most outcrossing species, opmental processes. For example, a trait may simply
including humans. The frequency of heterozygotes increase or decrease additively and gradually as þ or
(“heterozygosity”) at a locus in H-W equilibrium (2pipj) alleles (those that increase or decrease the character)
is often used as a measure of genetic variation at are substituted in the genotype; or there may be non-
that locus, since variation is maximized when allele linear effects, so that the character suddenly and
frequencies are equal. changes from one to another discretely different state
Phenotypic variation in most quantitative traits is when the number of þ alleles crosses a threshold.
continuous or almost so, because it is polygenic, based A gene commonly affects two or more characters
on segregating alleles at several or many loci, and also (pleiotropy), and so can contribute to a genetic correl-
includes environmental effects on the development or ation (rG) between them. Another possible cause of
expression of a character (Falconer and Mackay, 1996; genetic correlation is linkage disequilibrium, nonran-
Barton and Keightley, 2002). At many of the segregat- dom association of certain alleles at two or more loci
ing loci, the individual effects of alleles on the charac- within a population (e.g., an excess of AB and ab com-
ter typically are small, relative to the range of variation, binations and a deficiency of Ab and aB). A genetic
but substantially larger effects are commonly contrib- correlation caused by pleiotropy may be the net effect
uted by segregating alleles at a few loci. The variance in of both positive and negative components, since alleles
phenotype (VP) includes a genetic component (genetic at some loci may affect both characters in the same
variance, VG) and an environmental component (VE), direction, and at other loci, in opposite directions. The
and often an interaction effect (VG.E) as well. An value of rG depends on the frequencies and phenotypic
important component of VG is the “additive genetic effects of all contributing loci. It is estimated by the
variance” (VA), which is described by the correlation covariance between characters over a set of families,
between the phenotype of parents and their offspring; just as the genetic variance is estimated for a single
it is this component of variation that is most important character. Genetic correlations are important because
for evolution by natural selection. This component if the population mean of one character is altered,
consists of the “additive” effects of alleles, that is, the perhaps by natural selection, the other character will
phenotypic effect of each allelic substitution, averaged also be changed.
over all the genetic backgrounds in which it occurs. VA
depends on the number of loci contributing to the
character, on the evenness of allele frequencies at each GENETIC DRIFT
locus, and on the average magnitude of the phenotypic
effect of different alleles. (VA ¼ 2Spipja2 in the simplest Random genetic drift is simply random change in the
case, where a is the average phenotypic effect and frequency of alleles (and consequently, of genotypes).
S indicates summation over loci.) The ratio VA/VP is The genes carried by a generation of newly formed
Evolutionary Theory 5
zygotes in a population are a sample of the genes Since DNA sequence data have become available,
carried by the previous generation, to which the another theoretical approach to studying the dynamics
parents belong. Because of random sampling error, of genetic variation, coalescent theory, has become
the frequency (p) of an allele, say Ai, among the prominent (Hein et al., 2005). Looking back in time
zygotes is unlikely to be exactly the same as in the from the present, the gene copies (at a particular gene
previous generation, since there is likely to have locus) in the population today are descended from only
been random mortality and random variation in some of the genes carried by the previous generation’s
female reproduction (fecundity) and male reproduc- zygotes, due to sampling error; those zygotes in turn
tion (number of mates) among individuals in the carried genes descended from only some of those in
previous generation (here we are considering their parents’ generation; and so on. Pursuing this
random, not selective, variation in survival and logic, it is inevitable that all the gene copies in the
reproduction). So although the allele frequency in a population today are descended from one single ances-
new generation of N zygotes (carrying 2N genes if tral gene copy (one DNA molecule) at some time in
the species is diploid) is p on average (the same as in the past. The descendants of that gene form lineages
the previous generation), the frequency distribution of genes, replicating down through the generations to
of possible allele frequencies has a variance, given by the present time, the set of lineages forming a gene tree
the binomial expression Var (p) ¼ p(1–p)/(2N). This which, like a phylogenetic tree of species, portrays
may be conceptualized as the variation among a their ancestry back (“coalesces to”) the common ances-
large number of possible samples of 2N genes. The tral (CA) gene, which existed tCA generations ago. That
greater Var (p) is, the greater the random change in ancestor was one of some number (say, 2N) of genes in
allele frequency is likely to be, from generation to the population at that time, but the descendants of
generation, and thus the faster the process of evolu- those other genes have not persisted to the present
tionary change by genetic drift. The expression for time, due to random genetic drift. (When this history
Var (p) tells us that this happens faster, the smaller was first described for human mitochondrial DNA,
the population size N. N in this theory refers to the catchy phrase “mitochondrial Eve” was applied
the effective size of the population, which is smaller to the female that carried the ancestor of all human
than the “census size” if individuals vary in repro- mitochondrial genomes. Some people wrongly sup-
ductive rate, if the sex ratio among breeding individ- posed that this meant the ancestral human population
uals departs from 1:1, or if the population fluctuates consisted of only one woman [and presumably one
in size. man].) The speed of genetic drift depends on popula-
Since this variance holds in each generation, p tion size, so it will not be surprising to learn that for
fluctuates at random from generation to generation a population of constant effective population size N
with no corrective tendency to return to its starting (2N genes at a diploid locus), the average time back to
point, in a “random walk” to a boundary from which the common ancestor of all contemporary genes, tCA,
no return is possible: either loss of the allele Ai from the is 4N generations (e.g., four million if the effective
population or fixation of the allele Ai, i.e., attainment of population size is one million individuals).
p ¼ 1. (Movement away from this boundary is possible, A gene tree, representing the history of common
however, if new variation enters the population by ancestry of a sample of gene copies from one or more
mutation or by gene flow from other populations.) populations of a species, can be estimated by phylo-
Hence, genetic drift results in loss of genetic variation genetic methods, using as characters the mutational
within a population. differences (e.g., nucleotide substitutions) that have
If a number of separate populations of the species accrued among the lineages during their descent from
all began with the same initial p, different populations their common ancestor.
would have different random paths, and in principle
Ai would become fixed in some and lost in others;
thus, genetic drift results in variation (divergence) THE NEUTRAL THEORY OF MOLECULAR
among populations. An allele is more likely to be lost EVOLUTION
than to be fixed if its frequency is near zero, and
conversely if its frequency is near 1.0; in fact, the Building on these principles, Motoo Kimura pioneered
probability, at any time, t, that an allele will eventually the development of a neutral theory of molecular evo-
become fixed is pt, its frequency at that time. A new lution that is the basis for analyzing DNA sequence
mutation often exists, at first, as a single gene copy variation within and among species, and is often con-
among the 2N genes carried by the N individual sidered the “null hypothesis” against which alternative
organisms in a population, so its initial frequency is hypotheses, such as natural selection, must be com-
1/(2N), and this is its probability of fixation (if it is pared (Kimura, 1983; Nei and Kumar, 2000). Muta-
selectively neutral). tional changes occur at many sites in a DNA sequence,
at a total rate of, say, uT per gene per generation. suggest that some supposedly nonfunctional, “junk,”
Of these, suppose some fraction f is selectively neutral, DNA sequences may have unknown functions, perhaps
so the neutral mutation rate is u ¼ fuT. (The fraction in gene regulation.) The ratio o ¼ kA/kS, where kA and
f may depend on the functional role of a DNA sequence kS are the rates of nonsynonymous and synonymous
or the effect of a nucleotide change; for instance, a nucleotide substitution, respectively, is often used as
synonymous mutation in a functional gene or any muta- an index of the degree to which a protein-coding DNA
tion in a nonfunctional sequence such as a pseudogene sequence has been evolving neutrally, relatively free
is more likely to be selectively neutral than a nonsynon- of functional constraint. If all mutations have been
ymous mutation in a gene with a critical function.) selectively neutral, o should equal 1.
Since 2N genes are carried by (diploid) zygotes in each Genetic variation is lost from a population by gen-
generation, the total number of new mutations in etic drift, as we have seen. However, it is regenerated
the population each generation is 2Nu, on average. We by mutations at many sites in a DNA sequence, and
know from genetic drift theory that the probability of at equilibrium there exists variation in nucleotide
fixation of a new neutral mutation is 1/(2N) in a diploid sequence within a population, when the rate of input
population of constant size N, so 2Nu 1/(2N) ¼ u new by neutral mutation balances the rate of loss by genetic
mutations occur each generation that will eventually drift. A measure of polymorphism is the expected pro-
be fixed. The time to fixation, we have just learned, portion of base pairs that differ between two gene
is 4N generations, on average. Since this is the case copies taken at random (p) from a population. At equi-
each generation, u mutations should be fixed in a popu- librium this equals 4Nu, i.e., it is proportional to the
lation every generation on average. In other words, population size and the mutation rate. Consequently,
population-wide substitutions of nucleotides in a DNA effective population size can be estimated from p/4u.
sequence occur at a roughly constant rate, so DNA Because of polymorphism, the history of popula-
sequence evolution theoretically acts as a molecular tion separation may not be the same as the history of
clock, accumulating ut substitutions over the course of any one gene locus. Suppose an ancestral population
t generations. If two populations (or species) are derived divides into two populations (or species) A and B at
from a common ancestor and do not exchange genes time t1, and B later separates into populations B1 and
for t generations, and if mutations at different sites in B2 at time t2. Populations B1 and B2 are more closely
the DNA sequence are fixed in each population, the related to each other, by definition, than they are
difference D between sequences taken from the two to population A. If population B became fixed for a
populations will be D ¼ 2ut. If u (the neutral mutation new mutation, and thus for a different sequence than
rate, which can vary among genes because of functional population A, the mutation would be inherited by
differences or DNA repair processes) can be calibrated, populations B1 and B2 and provide evidence of their
then the time since the two populations separated sister-group relationship. Suppose, however, that popu-
can be estimated from the observed difference D, as lations A and B, and their common ancestor, have
t ¼ D/2u. (Calibration is usually based on geologically effective size N, and that the time between successive
dated events, such as fossils of the studied lineage or splits (between t1 and t2) is less than the 4N generations
related lineages, or separation of two land masses on required for one or another sequence variant to be fixed
which related taxa reside.) in each population by genetic drift. If the common
Eventually, D increases at a lower rate and levels ancestor is polymorphic for sequences x and y (per-
off, because mutational substitutions occur repeatedly haps differing by a new mutation in sequence x), fix-
at the same sites within the sequence, erasing evidence ation may not occur until after the three populations
of previous substitutions. This happens sooner for have become separate. Then one sequence (say, x) may
rapidly than slowly evolving sequences. According to be fixed in both A and one of the derived B-populations
the neutral theory, evolutionary change is more rapid (say B1), and the other sequence (y) may become fixed
if mutations do not affect organismal function, since in B2. The phylogeny of genes may be accurate (the
mutations that affect protein function are more likely gene copies in B1 are most closely related to those in A),
to be deleterious and eliminated by natural selection. but it would differ from the phylogeny of the popula-
Consequently, evolution is predicted, and found, to be tions. Therefore, it is important to use information
more rapid at third-base than second-base positions in from several or many independently inherited genes
codons, because third-base mutations are more often when analyzing the historical relationships among
synonymous. Sequence evolution is also more rapid in populations or species that have become separated
nonfunctional sequences, such as pseudogenes, than during a short time span.
in functional sequences. (Indeed, the rate of sequence Summarizing this section, note that for selectively
evolution between species is now used by molecular neutral mutations, whose fate is unaffected by natural
biologists to target functionally important versus less selection, the theory of genetic drift and the related
important sequences. This and other lines of evidence neutral theory of molecular evolution provide a basis
for many important inferences: e.g., inferring effective Let us consider selection among individual organ-
population size, time since separation of populations isms in a sexually reproducing population that differ in
(or since speciation), historical relationships among genotype at a single locus with two alleles, A and a.
populations, and whether or not natural selection has In the simplest case, the fittest of the three genotypes
affected DNA sequence divergence and polymorphism. AA, Aa, and aa is a homozygote. If aa is rare, because
the environment previously favored AA and has only
recently changed so that aa is now the fittest genotype,
NATURAL SELECTION we speak of directional selection for aa. Once aa
becomes the prevalent genotype, allele A, as well as
There are so many nuances to the concept of natural any other disadvantageous alleles that may arise by
selection that a simple, comprehensive definition is mutation, are reduced in frequency, and selection is
difficult to devise, but it may suffice, for present pur- often termed purifying. These are two faces of the same
poses, to define it as consistent (nonrandom) differences coin, selection that fixes the allele that, in homozygous
in the rate of survival or reproduction among classes of state, maximizes fitness. The frequency q of the advan-
entities that differ in inheritable characteristics. The tageous allele a attains the deterministic equilibrium
term “reproductive success” is often used for “survival q ¼ 1 if only selection is operating, but if other alleles
and reproduction,” since survival to reproductive age is repeatedly arise by mutation, the equilibrium fre-
prerequisite for reproduction. “Entities” is deliberately quency will be set by the mutation rate relative to the
vague, because selection can (in principle) act among strength of purifying selection (“mutation/selection
various kinds of biological “individuals,” such as genes balance”). Similarly, if a locally disadvantageous allele
or larger sections of genetic material, individual organ- (perhaps A) that is advantageous in a different geo-
isms, groups of conspecific organisms, species, or graphic population enters the population by gene flow,
clades (Williams, 1992). We speak of “classes” of genes, the genetic equilibrium is determined by the relative
individuals, etc., because we cannot tell if a difference strength of gene flow and purifying selection. Gene
in reproductive success is nonrandom from informa- flow from other populations can sometimes severely
tion about a single individual of each kind; we require diminish the degree of adaptation of populations to
samples of similar genes or individuals in order to see their local environment.
if there is a consistent difference between different Suppose the advantageous allele a is very rare,
types of alleles or phenotypically different organisms. either because it has recently originated by mutation
Natural selection, in distinction from genetic drift, is or because it has formerly been disadvantageous
marked by a consistent difference in mean reproduct- but nevertheless persisted in the population due to
ive success within a given environment, not a random, mutation/selection balance. If the frequencies of A
unpredictable difference; thus natural selection is the and a are p and q respectively, the Hardy–Weinberg
antithesis of chance. frequencies of the two genotypes that contain the a
allele, Aa and aa, are 2pq and q2, and the vast majority
of the a genes are carried by heterozygotes. (For
MODES OF SELECTION example, if q ¼ 0.01, 2pq ¼ 0.0198, q2 ¼ 0.0001, and
the ratio of heterozygotes to homozygotes is 198:1.)
Most analyses of evolution by natural selection are Whether or not the a allele can increase (or “invade”
concerned with individual selection: differences in fit- the population) depends almost entirely on the fitness
ness, owing to a genetically variable phenotypic charac- of Aa relative to the prevalent homozygous genotype
ter, among individual organisms within a population. (AA); at this stage the fitness of aa is almost irrelevant
In the simplest models, the character is affected by because it is so rare. This means that even if aa is the
variation at a single locus, and we suppose that the fittest genotype, the a allele will not increase if it
fitness of each genotype can be estimated. In practice, reduces the fitness of the heterozygote. This illustrates
this can be difficult, because fitness, defined as a geno- that natural selection acts only in the present, and
type’s relative rate of increase, i.e., growth in numbers cannot look forward toward the best possible outcome.
from one generation to the next, depends on several life- It also shows the value of the Hardy–Weinberg principle.
history parameters. The rate of increase is a complex Directional (or purifying) selection eliminates gen-
function of the probability of survival at each age from etic variation, but several other modes of selection
birth to the oldest reproductive age class, and on the (balancing selection) may maintain genetic polymorph-
age-specific values of female reproduction (fecundity) ism. The simplest model is heterozygous advantage,
and male reproduction (affected by mating success in which the fitness of Aa is greater than that of either
and sometimes by sperm competition). (In some cases, AA or aa, and all three genotypes segregate each gener-
it may be affected also by other complicating factors, ation due to random mating. Several hemoglobin poly-
such as genetic compatibility among uniting gametes.) morphisms in human populations, including sickle
cell hemoglobin, are the best-known of the few well- genetic make-up, so þ alleles rise in frequency. If the
documented examples of this mode of selection. fitness/phenotype relationship is “open-ended” (e.g.,
Unquestionably more important is frequency-dependent the unlikely circumstance that bigger is always better),
selection, in which the fitness of each genotype is a selection will ultimately favor the genotype with þ
decreasing function of its own frequency in the popu- alleles only (and subsequently, any mutations with still
lation, relative to other genotypes; that is, each geno- greater effects), so þ alleles become fixed at all loci,
type is more and more advantageous, the rarer it is. genetic variation is eliminated, and evolution ceases
Many biological phenomena, including competition except insofar as it continues to arise by mutation.
for resources, social interactions, and resistance to Thus the magnitude of the “mutational variance,” the
different genotypes of parasites, can give rise to such per-generation increment in the variance of the char-
frequency-dependent effects. Mathematically, this is a acter due to new mutations, will then limit the rate of
powerful way of maintaining multiple alleles in a popu- subsequent response to selection.
lation, and cases are known in which 100 or more What if the relationship between fitness and pheno-
alleles appear to be maintained this way. Variable type is not monotonic, but instead has an intermediate
selection, in which different homozygotes are advanta- maximum (“optimum”) that lies above the current
geous at different times or in different microhabitats mean phenotype? Directional selection will increase
within the area occupied by a breeding population, the frequency of þ alleles and bring the mean to the
can also maintain polymorphism, although this is by new optimum. The character then becomes subject to
no means guaranteed: mathematical models show that stabilizing selection: deviations in either direction
even if both homozygotes (AA and aa) are advanta- from the mean are disadvantageous. Many different
geous in different environmental states, only a rather combinations of þ and alleles can add up to give
narrow range of combinations of selection intensities the same optimal intermediate phenotypic value; some
and environmental frequencies will maintain all the of them are highly heterozygous, and others are homo-
genotypes indefinitely. (Note that persistence of both zygous for þ alleles at some loci and for alleles at
homozygotes because of their variable fitnesses also other loci. Mathematical theory has shown that one or
implies persistence of heterozygotes, due to random another of the homozygous genotypes will eventually
mating.) replace all the other genotypes, so that genetic vari-
The phenotypic implications of these genetic ation will be eliminated by stabilizing selection.
models depend on the relation between genotype and Studies of natural populations have shown that
phenotype. In simple cases, in which there is either the most common forms of selection on quantitative
complete dominance of one allele or additive inherit- phenotypic characteristics are stabilizing selection and
ance (in which the heterozygote’s phenotype is inter- disruptive (also called diversifying) selection, in which
mediate), persistent genetic polymorphism implies two or more phenotypes have higher fitness than do
persistence of two or three phenotypic classes, respect- the intermediates between them (Endler, 1986). Dis-
ively. Most of the consequences of the single-locus ruptive selection at a single locus generally implies that
models carry over into thinking about the effects of the heterozygote for two alleles A and a has lower
selection on a polygenic phenotypic trait, in which fitness than both homozygotes. Such a polymorphism
each variable locus contributes a small amount to over- is unstable, however, and the population will become
all variation. We consider the simplest case, an additive fixed for the initially more common allele. In models of
character, measured in, say, millimeters, for which “þ” disruptive selection on an additive polygenic character,
and “–” alleles at each of k loci add or subtract the same variation is not maintained indefinitely; instead, the
amount. The mean and variance of the character are population mean evolves to one or the other of the
determined by the frequency of the alleles at all of the superior phenotypes, and stabilizing selection then
loci; the mean will clearly be higher (and the variance takes over and reduces variation. In both the single-
lower) if most of the þ alleles have high frequency. locus and polygenic models, variation is maintained
However, an intermediate mean could result from only if disruptive selection is frequency-dependent,
many possible allele frequency arrays, ranging from a such that the fitness of the superior genotypes declines
highly variable population with p ¼ 0.5 (i.e., þ and as they become more abundant. The simplest example
equally frequent) at each locus, to fixation of a single would be if the genotypes are each adapted for a differ-
genotype that is homozygous for þ at half of the loci ent food or other limiting resource, so that competition
and for at the other half. becomes more intense, and fitness declines, as a par-
Directional selection on the character occurs when ticular genotype becomes more abundant and depletes
there is a monotonic relationship (at least over part of its resource.
the range of possible phenotypes) between phenotype I have introduced frequency-dependent selection
and fitness. For example, selection may favor larger as a negative feedback loop that can maintain stable
phenotypes, namely those with more þ alleles in their coexistence of different genotypes in a single breeding
population. It is possible, however, to imagine that the that together more than make up for the reproduction
fitness of individuals of a particular genotype increases foregone at an earlier age. On the other hand, if abun-
as the genotype’s frequency increases. This would dant inescapable predators make death at an early
be a form of positive feedback that hastens fixation of age virtually inevitable, selection will favor early
the genotype, eliminating variation. Such selection is reproduction, and mutations that defer senescence or
easily envisioned for many social behavioral traits, enhance fecundity at advanced ages may well be dis-
in which conformity to a predominant behavior pat- advantageous (if these effects reduce early fecundity).
tern might be advantageous. The evolution of intrinsic senescence and mortality
may therefore be affected by the age distribution of
extrinsic mortality factors. Many potential adaptations
COMPONENTS OF FITNESS have both benefits and costs, which may be environment-
dependent.
Genotypes may differ in fitness due to one or more A fitness component of particular interest is repro-
components, most of which are generally considered ductive success achieved through success in mating,
life history features (Stearns, 1992). These components which Darwin termed sexual selection (Andersson,
contribute to the rate of increase (numbers/time) of a 1994). In many species of animals, the variation in
genotype, relative to others. One may think of a popu- reproductive success, and therefore the potential inten-
lation of organisms as consisting of subpopulations of sity of sexual selection, is greater in males than in
different genotypes (or of alleles) that are all growing females. This difference is generally ascribed to the
like a bank account, with compound interest. All else smaller and far more abundant gametes of males than
being equal, a difference (in, say, survival probability females, but sexual selection acts more strongly on
or fecundity) expressed at an earlier age generally has females of some species (e.g., phalaropes and some
a bigger impact on growth in numbers (fitness) than a pipefish and seahorses), in which investment in pater-
similar difference expressed at a later age. Suppose nal care of offspring limits the number of a male’s
individuals reproduce from age three until ten, and potential mates. (Thus the “choosier” sex, that exerts
then die. A mutation that increases the chance of sur- stronger sexual selection on the opposite sex, usually
vival from age eight to nine has a smaller selective expends greater parental effort.) The two most com-
advantage than one that provides a similar survival monly discussed modes of sexual selection are conflict
advantage from age two to three, because survival between males, with winners gaining access to more
enhancement in the older age classes will have much females, and female “choice” of some males over
less effect on the number of offspring they might yet others, based on one or more characteristics that usu-
produce (and the number of genes passed on). Simi- ally are actively displayed to females. (In many cases,
larly, a mutation that increases reproductive output at the same trait seems to play a role in both male–male
age three has a greater impact on the increase of the and male–female interactions.) There is considerable
mutation’s frequency than if it affects reproduction at evidence that conflict between males selects for larger
age ten, because (a) fewer individuals survive to age size, greater weaponry, and many other kinds of traits
ten, so they don’t get the benefit of the mutation; that are used to establish dominance. The equilibrium
and (b) the mutation expressed at the younger age mean value of such a trait will be set by balance
effectively shortens the generation time, so more des- between the reproductive advantage it provides and
cendants (grandchildren, great-grandchildren . . .) are disadvantages such as its energy costs or effects on
produced per time unit than are produced by the geno- susceptibility to predation. Indeed, male investment
type whose reproductive capacity is enhanced only at in features that enhance mating success, such as
an older age. mating activity, weaponry, or display features, may
Consequently, mutations that enhance survival reduce investment in maintenance (e.g., immune
or the number of offspring (e.g., number of eggs or system) and survival.
young) are expected to increase fitness, but the magni- There is considerable evidence from birds, insects,
tude of increase depends on the age at which these and other animals that female “choice” imposes sexual
effects come into play. Moreover, there may exist selection, but there is considerable uncertainty about
trade-offs between different fitness components, or why females choose particular male phenotypes, such
between a given component expressed at different as males with more vigorous displays or more highly
ages, partly because an organism must partition elaborated ornaments or vocalizations. According to
energy or nutrients (e.g., protein) among different one hypothesis, exaggerated male features indicate
functions (the principle of allocation). For example, if high physiological vigor that may stem from superior
reproduction reduces growth, it may be advantageous genetic constitution (the “good genes” hypothesis), and
to delay reproduction until the individual is larger, females that choose such males will have fitter off-
which may ensure a longer life and higher fecundity spring. There is some support both for this hypothesis
and for several contenders. In models of runaway attempts to specify what the optimal character state
sexual selection, a nonrandom association (linkage dis- ought to be, given some assumptions about benefits,
equilibrium) develops between genes that affect a male costs, and constraints. This approach assumes that
ornament and genes that affect the degree of female there has been enough time and enough genetic vari-
preference for this character. Females that prefer more ation for natural selection to bring the mean character
highly ornamented males have daughters that inherit state in a population nearly to its optimum value, and
this preference (as well as unexpressed genes for large that the genetic details do not matter very much.
male ornamentation) and sons that inherit larger orna- Whether or not these are reasonable assumptions
ments (as well as unexpressed genes for heightened may depend on empirical information about such
female preference). (Note that most features expressed things as genetic variation and evolutionary history
by a single sex are encoded in the genome of both (e.g., inferences about how long a species has probably
sexes.) Therefore, any increase in the average male been subject to consistent environmental selection).
ornament in the population will cause a correlated Optimization is a common approach in the fields
increase in the average female preference, and vice of functional morphology and physiology, in which it is
versa, ratcheting both toward more extreme values assumed that fitness is enhanced by maximizing some
until the process is halted either by counteracting function, subject to constraints such as costs in energy
selection or by running out of genetic variation. or materials, or compromises with other functions.
In a twist on sexual selection theory, females and For example, aerodynamic models have been used to
males are engaged in sexual conflict: males reduce model flight and optimal wing morphology in birds,
females’ fitness in various ways (e.g., incessantly in which compromises among speed, maneuverability,
attempting to mate), females are selected to resist, and energy expenditure are taken into account. Among
and selection favors males with ever more stimulating nonsocial aspects of behavior, models of optimal for-
characteristics that can overcome female resistance aging describe when a foraging animal should give up
(Arnqvist and Rowe, 2005). The scope for such inter- searching in one patch and move to another.
actions appears greater than was formerly supposed, Social interactions entail complexities that make
because it is clear that females of many species mate genetic modeling difficult, and have been analyzed
with multiple males, even in species that form a sup- almost entirely by optimal models. The complexity
posedly monogamous pair bond. Thus males have the arises from the frequency-dependent fitness of differ-
potential of siring offspring by mating not only with ent trait values: the optimal behavior of an individual
unmated, but also with previously mated, females. often depends on the behavior of other members of the
The consequences include competition between sperm population. Among the most widely used approaches
from different males. Probably because of the strong, is game theory (Maynard Smith, 1982). Suppose, for
long-continued selection exerted by sperm competition example, that the problem is whether or not parental
and sexual selection, reproductive characteristics, care, by either or both mated partners, will evolve by
including male display features, genitalic morphology, individual selection. One might postulate two “strat-
proteins from accessory reproductive glands, sperm egies,” “Stay and provide care to offspring” and “Defect
morphology, and cell-surface proteins of gametes, are and attempt to reproduce again.” For each possible
rapidly evolving characteristics that often are the pair (S♀/S♂, S♀/D♂, D♀/S♂, D♀/D♂), one postulates
major differences among closely related species. for each partner the expected reproductive “payoff,”
which depends on both the benefit to each partner (in
terms of surviving offspring from this mating) and the
MODELING ADAPTATION costs to each (in terms of the likely reproductive success
sacrificed). The average fitness of each strategy, for
In considering components of fitness, we have moved each sex, is then its payoff averaged over the possible
from the very general theories of population and quan- pairings, and weighted by their frequency in a random-
titative genetics, which apply to unspecified genes and pairing population. The best strategy, within the set of
characters, to models of the evolution of specific strategies considered (here, S and D), is the one that, if
classes of characters, such as life history features. fixed in the population, will remain fixed even if indi-
Evolutionary analyses of adaptive evolution of specific viduals with alternative strategies attempt to invade.
classes of characters employ several approaches to This is the evolutionarily stable strategy, or ESS.
modeling (Bulmer, 1994). The evolution of some fea-
tures is best analyzed by genetic models. This is true
of models of sexual selection by female choice, for LEVELS OF SELECTION
example, because linkage disequilibrium is an essential
component and it requires an explicit genetic approach. Natural selection was defined above as “consistent
The major alternative is optimization, an approach that (nonrandom) differences in the rate of survival or
reproduction among classes of entities that differ in bearers on the reproductive success of individuals
inheritable characteristics.” These “entities” may be at (kin) who carry the same allele due to common des-
different, nested levels, and the effects of selection cent. (In this case, the “bearers” are parents, and the
at different levels may be opposite (Okasha, 2006). “kin” are their offspring.) In the same way, genes that
Consider, for example, the level “individual organism” enhance their bearers’ propensity to help more distant
and the level “somatic cell lineage” within a multicellu- relatives may increase in frequency – but the conse-
lar organism. If a cell lineage experiences a mutation quent increase in the relatives’ fitness must be greater,
that causes rapid, unrestricted cell division, that lin- since their probability of sharing the “helping allele” is
eage has a “selective advantage” relative to other cells, lower. William Hamilton formalized this relationship
and will constitute an increasing proportion of cells in what has become known as Hamilton’s rule, which
within the domain of the single organism (Nowak, states that “altruism” spreads if rb > c: an altruistic
2006). This proliferation – cancer – is clearly disadvan- trait can increase in frequency if the benefit (b)
tageous to the higher-level entity (the organism), if it received by the donor’s relatives, weighted by their
occurs before or during the organism’s reproductive relationship (r) to the donor, exceeds the cost (c) of
ages. Selection among genetically variable individual the trait to the donor’s fitness. The relationship, r,
organisms will favor genotypes that have the ability to between donor and recipient is the fraction of the
suppress cancerous tumors. donor’s genes that, on average, are identical by descent
We may likewise distinguish selection among indi- with any of the recipient’s genes. For example, r ¼ ½
vidual organisms with different genotypes (the level of between parent and offspring, so an allele for parental
selection assumed so far in this chapter) from selection care should spread, even if it costs the parent her life
at the level of the individual gene (locus). In asexual and subsequent reproduction, as long as her care
organisms, there is little conflict between selection results in survival of more than two extra offspring
at these levels, because the fate of a gene (survival, (compared to a parent that does not provide care).
passage to subsequent generations) depends on that (Kin selection is only one of several explanations
of the rest of the genotype to which it is bound. But of the evolution of co-operation among genes, cells,
in sexually reproducing organisms, conflicts can arise. or conspecific organisms. For example, reciprocity
A famous example is the “t locus” in house mice. More [“reciprocal altruism”] may evolve if individuals recog-
than 90% of the sperm of males heterozygous for a nize one another and can benefit others or not,
normal allele (T) and one of several recessive alleles depending on their history of behavior.)
(t) carry the t allele (an example of meiotic drive). Some Because of kin selection, the family (mated pair
of the recessive alleles cause embryonic death, and and associated offspring) is an obvious context in
others male sterility, in homozygous condition. The which co-operation may evolve. Nevertheless, intrafa-
differential transmission of T and t alleles constitutes milial interactions are riddled with conflict. Sexual
differential “reproduction” at the gametic level (genic conflict inevitably arises from the sex difference in
selection), opposing differential survival of individual gamete size (and some other features in some species):
mice (individual selection). Genic selection accounts male fitness can be increased by mating with many
for many phenomena, such as the proliferation of females, whereas all of a female’s eggs can usually be
transposable elements (“selfish genetic elements”): fertilized by a single male. Female fitness is more likely
DNA sequences that replicate more frequently than to be enhanced by her offspring’s survival, which may
most of the genome. be increased by parental care or by “genetic quality.”
Genic selection provides one way of viewing the Parental care increases the fitness of both parents, but
evolution of co-operation, which stands in contrast to it entails costs, including lost reproductive opportun-
the selfish individualism that generally characterizes ities. If offspring were as likely to survive with unipar-
individual selection (Dawkins, 1982; Sober and Wilson, ental care as with biparental care, selection would
1998). Cells in multicellular organisms co-operate favor defection by one sex – the one for which parental
because they are (generally) genetically identical: a care is more costly (Clutton-Brock, 1991). A further
gene in a liver cell is replicated by virtue of the replica- complication is that if a caregiver were not actually
tion of identical copies in the germ cell line – and the the parent of some or all of the offspring, he (or she)
fate of the germ cell line depends on the gene copies would have less of a genetic interest in their survival.
functioning in the liver. Likewise, the rate of increase “Extrapair copulation,” common in seemingly monog-
of a parent’s gene over generations depends on the amous species of birds, therefore alters the costs and
survival and replication of copies of that gene in benefits of parental care. In some species of primates
the parent’s offspring – and so alleles that program and other mammals, a male that replaces another male
parental care may increase in frequency. This is an kills his new mate’s offspring, since he has no genetic
example of kin selection: selection in which alleles interest in them, and killing them enables him to father
differ in fitness by influencing the effect of their his own offspring faster. (Killing some offspring can
also be advantageous to parents if, by reducing compe- of geographic range), species may differ in their
tition among the remaining offspring, it maximizes the probability of extinction or of speciation per unit time.
number of healthy survivors.) Stephen Jay Gould and others, pointing out that these
Trivers (1974) first pointed out that because a probabilities are the species-level analogues of differ-
parent maximizes her (his) fitness by allocating care ential mortality and reproductive rates of individual
among a number of offspring, present and future, the organisms, have proposed that species selection has
optimal investment of care in any one offspring is shaped the frequency distribution of traits in large
lower from the parent’s perspective than from the off- clades and biotas (Gould, 2002). The fraction of plant
spring’s. The consequent parent–offspring conflict has species with flowers, for example, greatly increased
many consequences for behavior, and even for preg- during the Mesozoic, and the world’s mammal fauna
nancy. Haig (1993, 1997) has described how genes became increasingly dominated by placental euther-
expressed in human and mouse fetuses that enhance ians in the late Mesozoic and Tertiary. Identifying the
uptake of sugar and other nutrients from the mother trait(s) that have been the “target” of species selection
are counteracted by maternally expressed genes that can be difficult, but is sometimes possible by compar-
prevent the fetus from extracting too much. For ing the diversification rate of multiple clades that
example, insulin levels are increased in pregnant have independently evolved a postulated diversity-
women, decreasing blood glucose (just when one enhancing feature, compared to the diversification rate
might expect it to be higher), in order to counteract a of sister clades that lack the feature. Herbivory in
fetal hormone that has the opposite effect. insects, sexual dichromatism in passerine birds, and
If an individual with an “altruism allele” dispenses low body mass in several orders of mammals seem
benefits indiscriminately to both related and unrelated to be associated with increased diversification (Coyne
individuals, the survival of both that allele and its and Orr, 2004).
nonaltruistic (“selfish”) alternative allele are equally
enhanced, but the donor suffers a cost (c), so the selfish
allele increases. As a rule, individual selfishness SPECIATION
increases within populations, even if the population
as a whole suffers. In principle, extinction of whole There are several contending concepts of “species”
populations of selfish individuals, and survival of because this word serves several purposes. As a term
populations of co-operative individuals, could cause in classification, it may simply label phenotypically
evolution of co-operation in the species as a whole. distinguishable populations. For instance, morpho-
This would be group selection (also called population logically different sections of a single lineage in the
selection and interdemic selection), in opposition to fossil record are sometimes given different names,
individual selection. Some authors hold that group and may be termed “chronospecies.” Many systematists
selection can play a role in evolution, especially if the use a phylogenetic species concept (PSC), according to
groups are very small and temporary (Wilson, 1983). which a species is a diagnosably different cluster of
(For example, if some groups of nestling birds include organisms, within which there is a parental pattern of
co-operators and others do not, the overall productivity ancestry and descent. This would include asexual
of those nests with co-operators may be higher, under forms. Most evolutionary biologists concerned with
some circumstances.) However, because populations evolutionary processes use one or another version of
of co-operators are likely to be invaded by immigrant the biological species concept (BSC), articulated by
selfish genotypes (“cheaters”), which rapidly increase Ernst Mayr in 1942. A biological species is a group of
within these populations, co-operation is unstable. actually or potentially interbreeding populations that
Most evolutionary theorists therefore conclude that are reproductively isolated (by biological differences)
group selection, evolution by differential extinction, from other such groups. The reproductive isolating
or reproductive productivity of whole populations, is barriers (RIBs), which are usually genetically based,
unlikely to play a major role in evolution. The import- include prezygotic barriers that reduce gene exchange
ant consequence is that we generally do not expect before zygote formation (e.g., differences in habitat
the evolution of characteristics that benefit the popula- association, timing of reproduction, behavior, pollin-
tion or species, but which are disadvantageous to the ation [for plants], and failure of gametes to unite) and
individual or its kin. postzygotic barriers that act after zygote formation, and
Selection among groups, as long as it does not are expressed as diminished survival or reproduction
oppose individual selection within groups, may how- of hybrid genotypes. The BSC applies only to sexual
ever have evolutionary consequences. These may be organisms and may be more difficult to apply in prac-
most evident when the groups are species. As a conse- tice than the PSC, since the potential ability of spatially
quence of characteristics of their constituent individ- separated (allopatric) populations to interbreed may be
uals, or of properties of the species as a whole (e.g., size difficult to evaluate. However, reproductive isolation
(RI) plays a critical role in long-term evolution, since it 2004). Only a few well-documented cases of sympatric
enables populations, even if they eventually meet and speciation (completed or in process) satisfy skeptics
overlap, to retain their distinct characteristics and to (Coyne and Orr, 2004).
generate clades of species that subsequently elaborate What causes the evolution of RI between spatially
those differences. It is even possible that speciation separated populations? As long as the populations are
facilitates sustained evolution of morphological and allopatric, there cannot be selection to avoid hybridiza-
other characteristics, by preventing the “slippage” that tion, so RI must evolve as a by-product of genetic
interbreeding with other populations would cause divergence that transpires for other reasons. Genetic
(Futuyma, 1987). drift, ecological selection, and sexual selection are the
There is abundant evidence that many species postulated processes, but it is only recently that this
of animals and plants form by genetic divergence of problem has been explicitly and rigorously studied.
spatially disjunct (allopatric) or neighboring (parapatric) Divergent sexual selection, resulting in different
populations of an ancestral species, since this reduces female preferences and male display traits, can result
gene flow enough to allow divergent changes in allele in behavioral isolation. There is considerable indirect
frequencies by natural selection or genetic drift. evidence for this hypothesis, in that the diversification
Whether or not species are often formed sympatrically, rate of clades of birds and insects with features indica-
i.e., by evolution of an intrinsic separation of a single tive of strong sexual selection has been higher than
randomly mating population into two reproductively that of sister clades lacking those features. The high
isolated forms, is controversial. Except for speciation rate of evolutionary divergence of genitalia, sperm, and
by chromosome doubling (polyploidy), which is other features associated with reproduction is consist-
common in plants but rare in animals, the evolution ent with this hypothesis. Diverse lines of evidence have
of RI between populations, like the evolution of most also recently pointed to divergent ecological selection
phenotypic differences, is gradual: arrays of popula- as a cause of RI. In some cases the effect of selection is
tions can be found that display all degrees of pre- or fairly direct: beak size differences among Darwin’s
postzygotic isolation from none to complete. Genetic finches, for example, are adaptations for feeding, but
analyses, correspondingly, show that RI is polygenic, also are used by females to discriminate among males.
based on contributions from several or many genes. In other cases, genes underlying ecological divergence
Thus it is common to find partially reproductively may contribute to RI pleiotropically; examples include
isolated populations (semispecies) that are not readily a correlation between copper tolerance and partial
classified as the same or as different species. Moreover hybrid sterility among monkeyflower populations,
and very importantly, hybridization between such and between adaptation to different host plants and
forms in nature can result in some parts of the genome behavioral isolation in some herbivorous insects.
readily “introgressing,” or penetrating from one semi- Genetic drift plays a role in Ernst Mayr’s (1954)
species into the other, while other parts of the genome influential hypothesis of founder-effect speciation (also
remain much more differentiated, because stronger called peripatric speciation). Mayr believed that select-
divergent natural selection on these regions counter- ive advantage of one allele over another depends
acts gene flow. strongly on which alleles it interacts with at other loci
Because RIBs are usually polygenic, full RI requires (epistasis for fitness). He postulated that a population
that two distinct clusters of different alleles be formed founded by few individuals will undergo genetic drift
at loci that affect a RIB (AABBCC. . . and aabbcc. . .), at some loci, so that some previously rare alleles
whereas recombination generates allelic mixtures become common by chance. This change in the
(AaBBCc. . ., etc.) that are only partially reproductively “genetic environment” alters selection at interacting
isolated and so form a “bridge” for gene exchange loci, so that previously disadvantageous alleles become
between diverging populations. An extrinsic barrier advantageous. Consequently, natural selection, initi-
(e.g., topography or unsuitable habitat) between diver- ated by genetic drift, alters the genetic constitution of
ging populations, if it is seldom surmounted by disper- the newly founded population so that it may become
sing individuals, reduces or eliminates this problem, reproductively isolated from the parent population.
which is why allopatric speciation is easy. After allo- There is little evidence for Mayr’s hypothesis, which
patric populations have diverged sufficiently, they may is considered implausible by some theoreticians,
expand their ranges and overlap without interbreeding. but new theoretical developments suggest that it still
Conversely, sympatric speciation is generally con- warrants consideration, albeit in modified form
sidered difficult because divergent selection, unaided (Gavrilets, 2004).
by an extrinsic barrier, must overcome recombination. If some genetic incompatibility has evolved
Several models have been proposed by which this may between allopatric populations, and if they subse-
occur, but the conditions and assumptions required quently expand their range, mate, and form hybrids
for sympatric speciation are fairly stringent (Gavrilets, with low fitness (i.e., low survival or reproduction),
individuals that mate conspecifically will have more repeatedly challenged, and it is certainly not possible to
successful offspring that those that hybridize, and affirm that mutations of large effect, that radically
alleles that enhance (reinforce) mating discrimination alter developmental pathways, have never contributed
may be transmitted and increase in frequency. Such to evolution. Some evolutionary changes have been
reinforcement of prezygotic isolation is the major con- discontinuous, such as neoteny in salamanders that
text in which there is direct selection for RI. It appears retain larval morphology into reproductive adulthood,
to be a fairly common component of speciation in and which is based on one or a few gene substitutions;
some taxa. but this is an abbreviation of a developmental pathway
The divergence of populations into distinct species that requires the action of many genes for its continu-
often includes ecological differentiation, often initiated ation. Mutations in key regulatory genes, such as
in allopatry due to environmental differences among the Hox genes that are important in establishing the
regions, and sometimes enhanced via character dis- fundamental body plans of animals, can have drastic
placement, the evolution of accentuated ecological effects, sometimes switching development of one body
difference between sympatric populations of two region into another; but whether or not comparable
species, to reduce competition. Bursts of speciation, mutations in these genes were the origin of major
accompanied by ecological divergence, are referred to evolutionary changes in body plan is not known.
as adaptive radiations, macroevolutionary episodes The complex developmental pathways that these genes
that account for much of the extraordinary adaptive now control may have evolved incrementally.
variety of organisms (Schluter, 2000). Classical evolutionary and embryological studies
of morphological differences among taxa identified
several common patterns, such as (a) allometric differ-
FROM MICROEVOLUTION ences: evolved differences in the rate at which one
TO MACROEVOLUTION structure or dimension grows compared to other struc-
tures (compare limb proportions in humans and apes);
Macroevolution, or evolution above the species level (b) heterochrony: differences in the timing of develop-
(Levinton, 2001), includes the evolution of “higher mental events, including initiation or cessation of
taxa,” which, most systematists today insist, should a structure’s growth (as in neotenic salamanders);
be monophyletic groups of species that are recognized (c) heterotopy: differences in the location on the body
by shared derived characters (synapomorphies), and where a feature develop (e.g., bone in the skin of arma-
which usually are phenotypically quite different from dillos); (d) individualization of repeated elements (e.g,
related higher taxa. At least among extant animals, for heterodont dentition of mammals compared to homo-
example, mammals differ substantially in skeletal and dont dentition of most “reptiles”); (e) “standardiza-
other features from other amniotes. During the 1930s tion,” or restriction of variation (e.g., digit number
and 1940s, the major authors of the Evolutionary was higher and more variable in the earliest tetrapods
Synthesis provided both theory and evidence that than in their pentadactylous descendants). A major
the evolution of the distinctive features of higher taxa challenge is to understand how differences in genes
consisted simply of incremental changes in each of are translated into such phenotypic changes, via their
the differentiating characters, attributable to the pro- effects on the processes by which such characters
cesses, outlined above, that operate within and during develop. Increasingly, this challenge is being met in
the formation of species (Simpson, 1953). The many the field of evolutionary developmental biology (EDB,
distinctive characters of mammals, for example, are or “evo-devo”), which is based on increased under-
a product of mosaic evolution: largely independent standing of how certain genes regulate the time and
evolution, often at different rates, of many distinct place of expression of other genes, often in hierarchical
features. Each such feature, it was postulated, evolves sequences of control (Carroll, 2007). For example,
by successive small steps rather than by large discrete changes in the expression pattern of certain Hox genes
jumps. Such gradual evolution has been paleonto- along the embryonic anterior-posterior axis in turn
logically documented for many skeletal features of control activation of other genes that govern the
mammals, and for many other lineages. Often, evolu- form of vertebrae. In snakes, most precaudal vertebrae
tion of a character is accelerated, and takes surprising have characteristic thoracic form, rather than sacral
directions, because a feature may serve a new and and other vertebral forms, due to changes in the
different function. domains of expression of certain Hox genes. Moreover,
This neo-Darwinian view affirmed Darwin’s hypo- new regulatory connections between genes have often
thesis that evolution is a gradual process – although, to evolved. For instance, although the canonical role
be sure, it can sometimes be quite rapid, which makes of Hox genes is specification of anterior-posterior
finding intermediate stages in an already very incom- domains of differentiation, a Hox locus also controls
plete fossil record even less likely. Gradualism has been the development of bristles on the legs of Drosophila.
Major challenges lie ahead in understanding how advances in developmental biology to understand the
changes in gene regulatory pathways evolve, and the evolution of phenotypes, and many other concerns.
extent to which understanding the genetic basis of New approaches are being developed to answer old
development can predict possible constraints on the but difficult questions, such as the causes of speci-
kind of phenotypic variation that can arise and be ation, the evolution of functionally integrated charac-
available to natural selection. Moreover, development teristics, and the conditions under which populations
is often responsive to environmental signals, so a geno- adapt to environmental change or become extinct – one
type often expresses phenotypic plasticity, the ability to of the most important questions now, when humans
develop a variety of adaptive phenotypic states (its are changing the Earth at a frightening pace.
norm of reaction) under different environmental con-
ditions (Pigliucci, 2001). Conversely, canalization, or
developmental buffering, can evolve: the capacity of a DISCUSSION POINTS
genotype to produce a consistent phenotype despite
potentially destabilization by environmental variation 1. Although evolution consists of genetic change, we
or gene mutations. Adaptive phenotypic plasticity and often do not have direct evidence that differences
canalization are under genetic control, but how they among individuals, populations, or related species
evolve is little understood. in a feature of interest have a genetic foundation.
Are there ways in which we can have more or less
confidence that interesting variation represents
EVOLUTIONARY THEORY TODAY evolved differences rather than direct environmen-
tal effects on the phenotype?
When Darwin referred to “my theory,” he was speaking 2. What kinds of evidence might we use to judge
of a little-tested hypothesis. Since then, all the major whether a character of interest, or a difference
elements of his theory – the common ancestry of all between populations or species, is an adaptation
organisms, the bifurcation of lineages in the origin of rather than the consequence of genetic drift?
species, the evolution of adaptations by the action of 3. In what ways is evolution a matter of chance
natural selection on hereditary variation, the diversifi- (random) versus a nonrandom process?
cation of species by adaptation to different ecological 4. How do functionally complex characters, such as
niches, or places in the “economy of nature” – have the vertebrate eye, evolve? Cast your answer both
been abundantly supported, elaborated, and extended. in historical, phenotypic terms and in terms of
When biologists speak today of “evolutionary theory,” genetics and selection.
they refer not to a speculation or hypothesis, but to 5. In what ways may DNA sequence data inform us
a mature scientific theory, an accepted complex of about the history of differentiation among human
general principles that explain a wide variety of natural populations and the causes of the differences
phenomena, as quantum theory and atomic theory do among them?
in the physical sciences. 6. Taking into account principles of evolutionary
No biologist today would think of publishing “new genetics and possible scenarios for environmental
evidence for evolution” – it hasn’t been a scientific change, do you expect adaptive evolutionary
issue for a century. However, although the major prin- changes to occur in human populations in the next
ciples of evolutionary theory have been increasingly few hundred years? If so, discuss what changes may
supported despite, and indeed because of, vast changes occur, and how. If not, why?
in biological knowledge, many questions remain
unanswered and substantial controversy persists, as it
does in all active sciences, about some important ques- REFERENCES
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2 The Study of Human Adaptation
A. Roberto Frisancho
INTRODUCTION systems of organs, to entire organisms. For example, the

lungs provide oxygen to the extracellular fluid to conti-
Ever since hominids left Africa, they have expanded nually replenish the oxygen that is being used by the cells,
throughout the world and have adapted to diverse the kidneys maintain constant ion concentrations, and
environments, and acquired specific biological and the gastrointestinal system provides nutrients.
cultural traits that have enabled them to survive in a Humans living in hot or cold climates must undergo
given area. The conceptual framework of research in additional functional adjustments to maintain thermal
biological anthropology is that evolutionary selection balance; these may comprise adjustments to the rate
processes have produced the human species and that of metabolism, avenues of heat loss, heat conservation,
these processes have produced a set of genetic charac- respiration, blood circulation, fluid and electrolyte
teristics, which adapted our evolving species to their transport, and exchange. In the same manner, persons
environment. Current investigations have demonstrated exposed to high altitudes must adjust through physio-
that the phenotype measured morphologically, physiological, chemical, and morphological mechanisms, such
logically, or biochemically is the product of genetic as increase in ventilation, increase in the oxygen-carrying
plasticity operating during development. Within this capacity of the blood resulting from an increased concen-
framework, it is assumed that some of the biological tration of red blood cells, and increased ability of
adjustments or adaptations people made to their natural tissues to utilize oxygen at low pressures. Failure to
and social environments have also modified how they activate the functional adaptive processes may result in
adjusted to subsequent environments. The adjustments failure to restore homeostasis; which in turn results in
we have made to improve our adaptations to a given the maladaptation of the organism and eventual incap-
environment have produced a new environment to acitation of the individual. Therefore homeostasis is a
which we, in turn, adapt in an ongoing process of new part and function of survival. The continued existence
stress and new adaptation. of a biological system implies that the system possesses
mechanisms that enable it to maintain its identity,
despite the endless pressures of environmental stresses
HOMEOSTASIS AND ENVIRONMENTAL (Proser, 1964). The complementary concepts of homeo-
STRESS stasis and adaptation are valid at all levels of biological
organization; they apply to social groups as well as to
Central to the study of adaptation is the concept of unicellular or multicellular organisms (Proser, 1964).
homeostasis and environmental stress. Environmental Homeostasis is a function of a dynamic interaction
stress is defined as any condition that disturbs the normal of feedback mechanisms whereby a given stimulus
functioning of the organism. Such interference eventu- elicits a response aimed at restoring the original equi-
ally causes a disturbance of internal homeostasis. librium. Several mathematical models of homeostasis
Homeostasis means the ability of the organism to main- have been proposed. In general, they show (as schema-
tain a stable internal environment despite diverse, disrup- tized in Figure 2.1) that when a primary stress disturbs
tive, external environmental influence (Proser, 1964). the homeostasis that exists between the organism and
On a functional level, all adaptive responses of the the environment the organism must resort either
organism or the individual are made to restore internal to biological or cultural-technological responses in
homeostasis. These controls operate in a hierarchy at order to function normally. For example, when faced
all levels of biological organization, from a single with heat stress, the organism may simply reduce its
biochemical pathway, to the mitochondria of a cell, to metabolic activity so all heat-producing processes
cells organized into tissues, tissues into organs and are slowed down, or may increase the activity of the
17
18 A. Roberto Frisancho
Lifetime:
habituation
Primary acclimation
stress acclimatization
Biological
responses Restores
Disturbs homeostasis
homeostasis Growth: between
between developmental organism
organism acclimatization and
and environment
environment Cultural– Decrease
technological environmental
responses stress
2.1. Schematization of adaptation process and mechanisms that enable individual or population
to maintain homeostasis in the face of primary environmental disturbing stress. From Frisancho (1993).
heat-loss mechanisms. In either case, the organism processes that enable them to function and to be adapted
may maintain homeostasis, but the physiological to their environment.
processes will occur at a different set point. The attain- Not all responses made by the organism can be
ment of full homeostasis or full functional adaptation, considered adaptive. Although a given response might
depending on the nature of the stress, may require not be adaptive per se, through its effect on another
short-term responses, such as those acquired during structure or function it may prove beneficial to the
acclimation or acclimatization, or may require expos- organism’s function. Conversely, a given adaptive
ure during the period of growth and development as in response may aid the organism in one function, but
developmental acclimatization. actually have negative effects on other functions or
In theory, the respective contributions of genetic and structures. Thus, within all areas of human endeavor
environmental factors vary with the developmental stage a given trait is considered adaptive when its beneficial
of the organism–the earlier the stage, the greater the effects outweigh the negative ones. In theory, this is a
influence of the environment and the greater the valid assumption, but in practice, due to the relative
plasticity of the organism (Proser, 1964; Timiras, 1972; nature of adaptation, it is quite difficult to determine
Frisancho, 1975, 1993). However, as will be shown, the the true adaptive value of a given response. Every
principle does not apply to all biological parameters; response must be considered in the context of the
it depends on the nature of the stress, the developmental environmental conditions in which the response was
stage of the organism, the type of organism, and the measured and within the perspective of the length of
particular functional process that is affected. For time of the study and the subject population.
example, an adult individual exposed to high-altitude
hypoxia through prolonged residence may attain a level
of adaptation that permits normal functioning in all ADAPTIVE PROCESSES
daily activities and as such we may consider him
adapted. However, when exposed to stress that requires The term adaptation is used in the broad generic sense
increased energy, such as strenuous exercise, this of functional adaptation, and it is applied to all levels of
individual may not prove to be fully adapted. On the other biological organization from individuals to populations.
hand, through cultural and technological adaptation, A basic premise of this approach is that adaptation is a
humans may actually modify and thus decrease the process whereby the organism has attained a beneficial
nature of the environmental stresses so that a new adjustment to the environment (Mayr, 1963; Lewontin,
microenvironment is created to which the organism 1957; Proser, 1964; Dubos, 1965; Baker, 1966; Lasker,
does not need to make any physiological responses. 1969; Mazess, 1973; Frisancho, 1975, 1993). This adjust-
For example, cultural and technological responses permit ment can be either temporary or permanent, acquired
humans to live under extreme conditions of cold stress either through short-term or lifetime processes, and may
with the result that some of the physiological processes involve physiological, structural, behavioral, or cultural
are not altered. However, on rare occasions, humans changes aimed at improving the organism’s functional
have been able to completely avoid an environmental performance in the face of environmental stresses.
stress. Witness the fact that the Eskimos, despite their If environmental stresses are conducive to differential
advanced technological adaptation to cold in their mortality and fertility, then adaptive changes may
everyday hunting activities, are exposed to periods of cold become established in the population through changes
stress and in response have developed biological in genetic composition and thus attain a level of
The Study of Human Adaptation 19
genetic adaptation. In this context, functional adapta- ACCLIMATIZATION

tion, along with cultural and genetic adaptation, is
viewed as part of a continuum in an adaptive process Acclimatization refers to changes occurring within
that enables individuals and populations to maintain the lifetime of an organism that reduce the strain
both internal and external environmental homeostasis. caused by stressful changes in the natural climate or
Therefore the concept of adaptation is applicable to all by complex environmental stresses (Eagan, 1963;
levels of biological organization from unicellular organ- Bligh and Johnson, 1973; Folk, 1974). If the adaptive
isms to the largest mammals and from individuals traits are acquired during the growth period of
to populations. This broad use of the concept of adapta- the organism, the process is referred to as either
tion is justified not only in theory but also because it developmental adaptation or developmental acclima-
is currently applied to all areas of human endeavor tization (Timiras, 1972; Frisancho, 1975, 1993). Stud-
so that no discipline can claim priority or exclusivity in ies on acclimatization are done with reference to both
the use of the term (Dubos, 1965). Functional adaptation major environmental stresses and several related
involves changes in organ system function, histology, secondary stresses. For example, any difference in
morphology, biochemical composition, anatomical the physiological and structural characteristics of
relationships, and body composition; either independ- subjects prior to and after residence in a tropical
ently or integrated in the organism as a whole. These environment is interpreted as a result of acclimatiza-
changes can occur through acclimation, habituation, tion to heat stress. In addition, because tropical
acclimatization or genetic adaptation. climates are also associated with nutritional and
disease stresses, individual or population differences
in function and structure may also be related to these
ACCLIMATION factors. On the other hand, in studies of acclimation
any possible differences are easily attributed to the
Acclimation refers to the adaptive biological changes major stress to which the experimental subject has
that occur in response to a single experimentally been exposed in the laboratory. For understanding
induced stress (Eagan, 1963; Folk, 1974) rather than to the basic physiological processes of adaptation, stud-
multiple stresses as occurring in acclimatization. As with ies on acclimation are certainly better than those of
acclimatization, changes occurring during the process acclimatization. However, since all organisms are
of growth may also be referred to as developmental never exposed to a single stress, but instead to
acclimation (Timiras, 1972; Frisancho, 1975, 1993). multiple stresses, a more realistic approach is that of
studying acclimatization responses. Thus, studies on
both acclimation and acclimatization are essential for
HABITUATION understanding the processes whereby the organism
adapts to a given environmental condition. This
Habituation implies a gradual reduction of responses rationale becomes even more important when the
to, or perception of, repeated stimulation (Eagan, aim is to understand the mechanisms whereby
1963; Folk, 1974). By extension, habituation refers to humans adapt to a given climatic area, since humans
the diminution of normal neural responses, for in a given area are not only exposed to diverse stresses
example, the decrease of sensations such as pain. Such but have also modified the nature and intensity of
changes can be generalized for the whole organism these stresses, as well as created new stresses for
(general habituation) or can be specific for a given part themselves and for generations to come.
of the organism (specific habituation). Habituation
necessarily depends on learning and conditioning;
which enable the organism to transfer an existing DEVELOPMENTAL ACCLIMATIZATION
response to a new stimulus. A common confusion is
that habituation can lead to adaptation. However, the The concept of developmental acclimatization (also
extent to which these physiological responses are referred to as developmental adaptation) is based
important in maintaining homeostasis depends on upon the fact that the organism’s plasticity and suscep-
the severity of environmental stress. For example, with tibility to environmental influence is inversely related
severe cold stress or low oxygen availability, failure to to developmental states of the organism, so that the
respond physiologically may endanger the well-being younger the individual the greater is the influence
and survival of the organism. Likewise, getting used to of the environment and the greater the organism’s
tolerating high levels of noise implies ignoring the plasticity (Frisancho, 1975, 1993; Frisancho and
stress, which eventually can lead to deafness. In other Schechter, 1997). Hence, variability in physiological
words, habituation is a process that in the long run traits can be traced to the developmental history of
produces negative side effects. the individual.
ACCOMMODATION AND ADAPTATION is an important mechanism that facilitates human

biological adaptation (Thomas, 1975; Rappaport, 1976;
The term accommodation is used to describe responses Moran, 1979). It may be said that cultural adaptation
to environmental stresses that are not wholly success- during both contemporary times and in an evolutionary
ful because, even though they favor survival of the perspective, represents humanity’s most important tool.
individual, they also result in significant losses in some It is through cultural adaptation that humans have
important functions (Waterlow, 1990). For example, been able to survive and colonize far into the zones
subjects when exposed to a low intake of leucine for of extreme environmental conditions. Humans have
three weeks can achieve body leucine balance at the adapted to cold environments by inventing fire and
expense of reducing protein synthesis and protein clothing, building houses, and harnessing new sources
turnover (Young and Marchini, 1990). Since low of energy. The construction of houses, use of clothing in
protein synthesis and protein turnover diminishes the diverse climates, certain behavioral patterns, and work
individual’s capacity to successfully withstand major habits, represent biological and cultural adaptations to
stresses, such as infectious diseases (Frenk, 1986), climatic stress. The development of medicine, from its
under conditions of low-dietary protein intake achiev- primitive manifestations to its high levels in the present
ing body leucine balance represents only a temporary era, and the increase of energy production associated
accommodation, which in the long run is not adaptive. with agricultural and industrial revolutions are represen-
In other words, accommodation is a stopgap that tative of human cultural adaptation to the physical
ultimately produces negative side effects. environment.
Culture and technology have facilitated biological
adaptation, yet they have also created, and continue to
INDIVIDUALS VERSUS POPULATIONS
create, new stressful conditions that require new adap-
tive responses. A modification of one environmental
Whatever the method employed, geographical or experi-
condition may result in the change of another, and
mental research in human adaptation is concerned with
such a change may eventually result in the creation of
populations, not with individuals; although the research
a new stressful condition. Advances in the medical
itself is based on individuals. There are two related
sciences have successfully reduced infant and adult
reasons for this.
mortality to the extent that the world population is
The first is a practical consideration. Studying all
growing at an explosive rate, and unless world food
members of a given population, unless its size is small
resources are increased, the twenty-first century will
enough, is too difficult to be attempted by any research
witness a world famine. Western technology, although
team. Therefore, according to the objectives of the
upgrading living standards, has also created a polluted
investigation, the research centers on a sample that is
environment that may become unfit for good health
considered representative of the entire population.
and life. If this process continues unchecked,
Based on these studies, the researchers present a
environmental pollution will eventually become
picture of the population as a whole, with respect to
another selective force to which humans must adapt
the problem being investigated.
through biological or cultural processes, or else face
The second reason is a theoretical one. In the study
extinction. Likewise, cultural and technological adap-
of adaptation, we usually focus on populations rather
tation has resulted in the rapid increase of energy
than on individuals because it is the population that
availability and has decreased energy expenditure;
survives and perpetuates itself. In the investigation
causing a disproportionate increase in the develop-
of biological evolution, the relevant population is the
ment of degenerative diseases associated with meta-
breeding population because it is a vehicle for the
bolic syndrome. This mismatch between biology and
gene pool, which is the means for change and hence
lifestyle threatens our survival as human species
evolution. The study of an individual phenomenon
(Eaton et al., 2002). Therefore, adaptation to the world
is only a means to understand the process. The adapta-
of today may be incompatible with survival in the
tion of any individual or individuals merely reflects the
world of tomorrow unless humans learn to adjust their
adaptation that has been achieved by the population of
cultural and biological capacities.
which he is a member.
CULTURAL AND TECHNOLOGICAL GENETIC ADAPTATION AND ADAPTABILITY

ADAPTATION
Genetic adaptation refers to specific heritable charac-
Cultural adaptation refers to the nonbiological responses teristics that favor tolerance and survival of an
of the individual or population to modify or ameliorate individual or a population in a particular total envir-
an environmental stress. As such, cultural adaptation onment. A given biological trait is considered genetic
when it is unique to the individual or population and

Environmental influences
when it can be shown that it is acquired through during growth and development
biological inheritance. A genetic adaptation becomes have a high influence and
established through the action of natural selection elicit a high morphological
(Neel, 1962; Livingstone, 1958; Neel et al., 1998; Mayr, response
1997). Natural selection refers to the mechanisms
whereby the genotypes of those individuals showing
the greatest adaptation or “fitness” (leaving the most Morphological
Genetic Genetic
descendents through reduced mortality and increased phenotypic
trait mediation
fertility) will be perpetuated, and those less adapted to response
the environment will contribute fewer genes to the
population gene pool. Natural selection favors the
features of an organism that bring it into a more Environmental influences
efficient relationship with its environment. Those during adulthood
gene combinations fostering the best-adapted pheno- have a low influence and
types will be “selected for,” and inferior genotypes will elicit a low morphological
response
be eliminated.
The selective forces for humans, as for other 2.2. Schematization of interaction of genetic and environment
mammals, include the sum total of factors in the nat- and the phenotypic morphological outcome. Morphological and
ural environment. All the natural conditions, such as physiological diversity reflects the responses and adaptations
that the organism makes to particular environment during and
hot and cold climates and oxygen-poor environments,
development. From Frisancho (1993).
are potential selective forces. Food is a selective force
by its own abundance, eliminating those susceptible to
obesity and cardiac failures, or by its very scarcity, and individual flexibility. Extinct populations are those
favoring smaller size and slower growth. In the same which were unable to meet the challenges of new
manner, disease is a powerful selective agent, favoring conditions. Thus, contemporary fitness requires both
in each generation those with better immunity. The genetic uniformity and genetic variability.
natural world is full of forces that make some individ- Contemporary adaptation of human beings is both
uals, and by inference some populations, better the result of their past and their present adaptability
adapted than others because no two individuals or (Lasker, 1969; Frisancho, 1993). It is this capacity to
populations have the same capacity of adaptation. adapt that enables them to be in a dynamic equilibrium
The maladapted population will tend to have lower in their biological niche. It is the nature of the living
fertility and/or higher mortality than that of the organism to be part of an ecosystem whereby it modifies
adapted population. the environment and, in turn, is also affected by
The capacity for adaptation (adaptability) to envir- such modification. The maintenance of this dynamic
onmental stress varies between populations and even equilibrium represents homeostasis; which, in essence,
between individuals. The fitness of an individual or reflects the ability to survive in varying environments
population is determined by its total adaptation to the (Dubos, 1965; Proser, 1964). The ecosystem is the
environment – genetic, physiological, and behavioral fundamental biological entity – the living individual
(or cultural). Fitness, in genetic terms, includes more satisfying its needs in a dynamic relation to its habitat.
than just the ability to survive and reproduce in a given In Darwinian terms, the ecosystem is the setting for
environment; it must include the capacity for future the struggle for existence, efficiency and survival are
survival in future environments. The long-range fitness the measures of fitness, and natural selection is the
of a population depends on its genetic stability and process underlying all products (Proser, 1964).
variability. The greater the adaptation, the longer the In general, the morphological and functional features
individual or population will survive, and the greater reflect the adaptability or capacity of the organism to
the advantage in leaving progeny resembling the respond and adapt to a particular environment
parents. In a fixed environment, all characteristics (Figure 2.2). The effect and responses to a given environ-
could be under rigid genetic control with maximum mental condition are directly related to the developmental
adaptation to the environment. On the other hand, in stage of organism; so that the younger the age, the
a changing environment a certain amount of variabil- greater the effect and the greater the flexibility to respond
ity is necessary to ensure that the population will and adapt. Conversely, the later the age and, especially
survive environmental change. This requirement for during adulthood, the effect of the environment is less
variability can be fulfilled either genetically or pheno- likely to be permanent and the capacity to respond and
typically or both. In most populations a compromise adapt is also diminished when compared to a developing
exists between the production of a variety of genotypes organism.
MULTILEVEL SELECTION AND EVOLUTION single defector (Traulsen and Nowawk, 2006). Hence,
OF CO-OPERATION this simple condition ensures that selection favors
co-operators and opposes defectors.
Ever since Darwin (1871) indicated that the competi- The concept of group selection has been a major
tion between groups can lead to selection of co-opera- tenet of behavioral ecology. The major premise of
tive behavior, the concept of multilevel selection has behavioral evolutionary ecology is that genetic and
been developed. He stated that, “there can be no doubt behavioral traits are two distinct expressions of a
that a tribe including many members who were single evolutionary process. (Trivers, 1971; Cronk,
always ready to give aid to each other and to sacrifice 1991; Strier, 2000; Silk, 2001). In behavioral ecology,
themselves for the common good, would be victorious behaviors are treated like any other biological trait
over other tribes; and this would be natural selection” and are potentially subject to natural selection. The
(Darwin, 1871, p. 166). Over many years, Wilson and processes involved in behavioral evolution are
colleagues have been the main proponent of the idea of equivalent to those in genetic evolution: natural selec-
group selection (Wilson, 1975; Sober and Wilson, 1998; tion influences the frequency of a trait transmitted
Traulsen and Nowak, 2006). It is assumed that group from parent to offspring through differential fertility
selection is an important organizing principle that and mortality. In the evolutionary perspective, bio-
permeates evolutionary processes from the emergence logical structures have been custom tailored to motiv-
of the first cells to development of nations. According ate behaviors that are likely to enhance individual
to multilevel selection, groups consist of genetically fitness. Therefore, behavioral variants with a high
unrelated individuals, and successful groups attract fitness have been favored and these perpetuate the
new individuals, which learn the strategies of others evolutionary origin of fitness-enhancing biological
in the same group. A population can be subdivided traits. It follows then, that the behavioral traits that
into groups, and the individuals interact with other enhance fitness also accentuate biological fitness.
members of the group, and depending on their repro- In other words, a change occurring in one system
ductive fitness, individuals can lead to larger groups entails a change in the fitness governing evolution in
that split more often. In other words, higher-level or the other system. Therefore, both genetic and behav-
group selection emerges as a by-product of individual ioral selection tend to favor those existing variants
reproduction. whose net effect is to increase the average fitness
A fundamental condition for the success of the of the individual and population to the prevailing
group, therefore, must be co-operation among indi- conditions. Studies of primates indicate that they
viduals, and thus group selection favors co-operative use a diversity of behaviors that increase the likeli-
altruistic behavior and opposes defectors. The fitness hood of gaining access to mates and guarantee the
of an individual, and the group at large, also depends survival of their offspring; which, in turn, insures the
on the altruistic behavior of nonrelatives. When an passing of their traits to the next generation. In this
altruist gives an alarm call, it benefits not only his or context, behavioral actions that lead to a higher
her relatives, but also other unrelated members of reproductive success will become adaptive and the
the group because a primate troop does not only genes associated with such behavior will be trans-
include relatives. Thus, altruism can be selected ferred to the next generation faster than those that
if these nonrelated individuals can be counted on to are less adaptive. Therefore, the differences in fitness
reciprocate the favor when the need arises. between individuals and populations will determine
A recipient of an altruistic behavior who fails to recip- the behavioral pattern of a given primate group.
rocate is a cheater. Studies of nonhuman primates In other words, a specific behavioral strategy that
indicate that a cheater may gain in the short run by contributes to the survival and reproductive fitness
receiving aid without any costs to their own fitness of the individual – and eventually the population –
(Strier, 2000). However, reciprocity is necessary becomes part of the genetic milieu of the species.
for future support in the long run because the In summary, co-operation and altruism evolve by
cheater’s fitness is lower when compared to the group selection or multilevel selection. Human behav-
individual who reciprocated. In view of the fact that ioral ecology rests upon a foundation of evolutionary
primates constantly need to protect themselves from theory, which include sexual selection, whereby indi-
neighboring communities and predators, one can viduals within one sex secure mates and produce
assume that reciprocal altruism must have been offspring at the expense of other individuals within
selected for because it enhanced their fitness, not the same sex, which can cause changes in gene
because the animals are conscious of their motives frequency across generations that are driven at least
or the reproductive consequences of their behavior. in part by interactions between related individuals
Mathematical models indicate that a single co- referred to as kin selection, and be expressed as the
operator has a greater fixation probability than a sum of an individual’s own reproductive success.
CURRENT DIRECTIONS IN ADAPTATION mellitus was a quick insulin trigger. Insulin’s main func-
RESEARCH tion is to assist in the homeostasis of glucose in the
blood. Specifically, when blood glucose levels are too
In the 1970s I postulated the hypothesis of develop- high, the pancreas releases insulin to increase tissue
mental adaptation to explain the enlarged lung volume uptake of glucose, thus reducing blood glucose levels.
and enhanced aerobic capacity that characterize the Conversely, when blood glucose levels are low, the
Andean high altitude natives. According to the organism secretes glucagon and growth hormone, which
developmental adaptation hypothesis, “adult biological in turn, induce the release of stored glucose and fatty
traits are the result of the effects of the environment acids into the blood stream raising serum glucose levels.
and the physiological responses that the organism The insulin response is to activate an uptake of glucose
makes during the developmental state” (Frisancho, into the muscle cells for storage, and in liver cells it
1970, 1975, 1977). This concept is based upon the fact influences the conversion of glucose to fatty acids for
that the organism’s plasticity and susceptibility to envir- storage in fat (adipose) tissue. This response was an
onmental influence is inversely related to developmen- asset during times of abundance because it would allow
tal states of the organism, so that the younger the an individual to build-up energy reserves more quickly
individual the greater is the influence of the environ- and thus better survive times of food scarcity. Under
ment and the greater the organism’s plasticity these conditions, the thrifty gene was selected to regulate
(Frisancho, 1975, 1977, 1993). Hence, variability in efficient intake and utilization of fuel stores. In other
physiological traits can be traced to the developmental words, during periods of food shortage and famine,
history of the individual (Figure 2.2). Currently this those with the thrifty genotype would have a selective
concept has been applied to explain the variability in advantage because they relied on larger, previously
adult behavioral traits such as in learning and crime and stored energy to maintain homeostasis; whereas those
delinquency (Yueh-Au Chien, 1994; Sroufe et al., 2005; without “thrifty” genotypes would be at a disadvantage
Kruger et al., 2008), in sensory inputs and auditory and less likely to survive and reproduce. However, under
spatial processing (Martin and Martin, 2002), in toler- modern conditions of abundant food and sedentary
ance to surgical intervention (Faury et al., 2003), in lifestyle, this genotype becomes perversely disadvanta-
variability in oxygen consumption and mitochondrial geous. With a constant abundance of food, insulin levels
membrane potential in energy metabolism of rat remain high, resulting in tissues becoming less sensitive
cortical neurons (Schuchmann et al., 2005), and in to the effects of insulin. This reduced sensitivity to the
variability in increased risk of adult obesity and cardio- effects of insulin results in chronically elevated blood
vascular problems associated with the metabolic glucose levels type II diabetes and related chronic health
syndrome (Barker, 1994). A common denominator of problems (e.g., obesity).
all these studies is that humans and many other A test of the genetic predisposition to type II
organisms are conditioned by experiences during devel- diabetes involved a comparative study of the Pima
opment and as developmental experiences is an import- Indians of southern Arizona and the Pima Indians of
ant contributor to variability in adult phenotypic the Sierra Madre mountains of northern Mexico
behavioral and biological traits. (Knowler et al., 1990; Price et al., 1992). These two
In this section I will summarize the evidence groups, which were separated 700 1000 years ago,
supporting the applicability of the concept of develop- differ in their life style. The Arizona Pima live under
mental adaptation to account for the origins of the high conditions of access to a high fat, highly refined diet
risk of the adult metabolic syndrome incorporating and low energy expenditure. In contrast, the Mexican
information derived from thrifty gene, thrifty pheno- Pima still pursue a much more traditional lifestyle
type, and epigenetics. The evolution of the metabolic and have a diet based on the occasional intake of
syndrome is also discussed at length in Chapter 30 of lamb and poultry, but mainly on beans, corn, and
this volume. potatoes, grown by traditional, and physically very
energy-demanding, techniques. These two groups
differ significantly in the frequency of obesity and
DEVELOPMENTAL ADAPTATION AND THE diabetes. The Arizona Pima adults have a body mass
THRIFTY GENOTYPE index (BMI) of 33.4 kg/m2; compared to a BMI of 24.9
kg/m2 in the Mexican Pima (Ravussin et al., 1994).
Neel and colleagues (Neel, 1962; Neel et al., 1998) Likewise, in the Arizona Pima 37% of men and 54%
attempted to explain the epidemic proportions of of women were diabetic, while in the Mexican Pima
diabetes in Native American populations, such as the only 2 of 19 women and 1 of 16 men were diabetic
Pima Native Americans, by postulating the existence of (Knowler et al., 1990; Price et al., 1992). In other
a “thrifty gene” that increased the risk of type II diabetes. words, although the Mexican Pima share the “thrifty
According to this hypothesis, the basic defect in diabetes gene” with Arizona Pima, their increased frequency of
obesity and diabetes is more evidence that an abun- Poor maternal nutrition
dance of fatty foods and modern sedentary lifestyles associated with fetal
undernutrition
are the real culprits. Thus, it is not the presence of a
“thrifty gene” alone that results in increased rates of
diabetes, but rather the interaction with modern diet- Fetal programing: Cellular,
ary and lifestyle conditions the results in increased physiological, and metabolic
rates of the chronic health problems. compensatory responses
resulting in energy conservation
In summary, the thrifty genotype hypothesis has
been used to explain the epidemic levels of obesity
and diabetes among non-Western populations, such Adult poor Adult good
postnatal postnatal
as South Pacific Islanders, sub-Saharan Africans,
nutrition and high nutrition and low
Native Americans in the southwestern United States, energy energy
Inuit, Australian aborigines, etc. (Eaton et al., 1988; expenditure expenditure
O’Dea, 1991); all of whom were newly introduced to
industrialized diets and environments. The fact that
the frequency of type II diabetes has recently increased Nondiabetic Type II diabetic
and good health and polor health
among Europeans that were not subjected to periodic
famines cannot be attributed to the action of a 2.3. The thrifty phenotype. The risk of type II diabetes and
so-called “thrifty” gene. metabolic syndrome in adulthood is associated with prenatal
undernutrition resulting in efficient physiological adaptation that
becomes detrimental when food is abundant and energy
expenditure is low.
DEVELOPMENTAL ADAPTATION AND
THE THRIFTY PHENOTYPE
the Dutch famine of World War II were found to have
Recently, Barker and colleagues (Barker, 2007; Hales impaired glucose tolerance and increased adiposity
and Barker, 1992) have reported an inverse relationship in adulthood (Stein et al., 1975, 2007).
between birthweight and the risk of hypertension,
cardiovascular disease, and type II diabetes in adulthood
when the individual is well nourished postnatally. DEVELOPMENTAL ADAPTATION AND
To account for these observations, Barker and colleagues EPIGENETICS
proposed that adverse effects in utero induce cellular,
physiological, and metabolic compensatory responses, Epigenetics refers to the transmission of phenotypic
such as insulin resistance, high blood plasma levels of traits from one generation to the next that do not
fatty acids, which result in energy conservation and depend on differences in DNA sequence (Waddington,
reduced somatic growth that enable the fetus to survive 1952; Jablonka, 2004; Holliday, 2006). During the last
undernutrition. This response is referred to as the thrifty two decades, there has been an accumulation of obser-
phenotype hypothesis (Armitage et al., 2005). These vations indicating that the expression of DNA traits can
responses that were adaptive under poor prenatal condi- be affected by environmental factors acting during
tions become a problem if food becomes abundant. development. Specifically, experimental studies
In this view, thrifty physiological mechanisms are showed that identical twin mice differ in the color of
adaptive in nutritionally poor environments, but in rich fur; one has brown fur and will grow up to be lean and
environments are maladaptive. That is, what was positive healthy, while the other has yellow fur and becomes
under reduced availability of nutrients, particularly obese and prone to cardiovascular disease. The differ-
during periods of rapid development, becomes negative ent phenotypes are due to the addition of a methyl
in rich environments because it facilitates nutrient group (-CH3); which is referred to as methylation.
absorption and hence increases the risk of adult obesity
and the suite of risk factors for cardiovascular disease
Methylation
known as the metabolic syndrome (Figure 2.3).
In summary, it appears that nutrition and other Methylation refers to the altering of the genetic envir-
environmental factors during prenatal and early post- onment through the addition of a methyl group (-CH3)
natal development influence cellular plasticity; thereby to the fifth position of cytosine, which is largely
altering susceptibility to adult cardiovascular disease, confined to CpG dinucleotides. This addition, by modi-
type II diabetes, obesity, and other chronic diseases fying the CpG islands, prevents signaling molecules
referred as the adult metabolic syndrome. This hypoth- from reaching the promoter site to turn the gene on
esis is supported by the finding that the offspring of and prevent the expression of the dark coat color.
women who were starved and became pregnant during In other words, the additional methyl group attaches
to and shuts off the gene that controls dark fur color the organism; so that the younger the individual, the
and allows the yellow color to be expressed. Thus, the greater the epigenetic marks, including CpG methyla-
process of methylation works as a kind epigenome that tion. Despite the great interest in molecular genetics,
dictates which genes in the genome are turned on and there is scant incontrovertible evidence indicating
which are not. This process can differ even between epigenetic effects in humans. Considering society’s
identical twins. increased concern about environmental pollutants, this
Recently, experimental studies indicate that area of research should a good direction for human
bisphenol A (BPA) can alter gene expression and biologists.
affect adult phenotype by modifying CpG methylation
at critical epigenetically labile genomic regions (Water-
land and Jirtle, 2004). Bisphenol A is used in the produc- OVERVIEW
tion of polycarbonate and plastic containers and in
the organism acts like the body’s own hormones. Thus, The term adaptation encompasses the physiological,
there is concern that long-term exposure to BPA may cultural, and genetic adaptations that permit individ-
induce chronic toxicity in humans (vom Saal and uals and populations to adjust to the environment in
Hughes, 2005). Fortunately, the effects of methylation which they live. These adjustments are complex, and
are not permanent but reversible, as shown by the fact the concept of adaptation cannot be reduced to a simple
that the yellow agouti (Avy), whose diet was supple- rigid definition without oversimplification. The func-
mented with folic acid, vitamin B12, choline, betaine, tional approach in using the adaptation concept permits
and zinc, counteracted the DNA methylation and its application to all levels of biological organization
changed coat color from yellow to dark brown coat from unicellular to multicellular organisms, from early
(Dolinoy and Jirtle, 2008), which is associated with a embryonic to adult stages, and from individuals to popu-
low risk of cardiovascular disease. lations. In this context, human biological responses to
environmental stress can be considered as part of a
continuous process whereby past adaptations are modi-
Transgenerational epigenetic effects
fied and developed to permit the organism to function
It has been suggested that the epigenetic modifications and maintain equilibrium within the environment to
brought about by parental conditions may be which it is daily exposed.
expressed even in grandchildren. Extensive records of The mechanisms for attaining full functional adap-
a population in Overkalix cohorts, northern Sweden, tation include acclimation, acclimatization, habitu-
found that an association between grandparental ation, and accommodation. The role played by each
prepubertal slow growth periods (SGP) or rapid of these processes depends on the nature of the stress
growth periods (RGP), and parental periods of low or or stresses, the organ system involved, and the devel-
high food availability, with grandchildren’s mortality opmental stage of the organism. It is emphasized that
and disease risk (Kaati et al., 2007). If the SGP of the the goal of the organism’s responses to a given stress is
grandparent was a period of high food availability, to maintain homeostasis within an acceptable normal
then the male grandchild had reduced longevity but range with itself and with respect to other organisms
an increased mortality. The extent to which these and the environment (as schematized in Figure 2.1).
associations represent multigenerational epigenetic Such adaptations are usually reversible, but the revers-
effects is unwarranted, in part because ruling out ibility depends on the developmental stage of the
genetic and societal confounders, and in the absence organism at which the adaptive response occurs and
of molecular evidence, is extremely difficult. Hence, the nature of the environmental stress. This character-
future research must be focused on long-term transge- istic allows organisms to adapt to a wide range of
nerational studies whereby many birth cohorts are environmental conditions. Furthermore, an adaptation
studied using intensive prenatal and perinatal genotyp- is always a compromise between positive and negative
ing across generations. Only then can variability in the effects. Every adaptation involves a cost. The process
expression of phenotypic traits can be attributed to of adaptation is always positively beneficial; without
epigenetic changes. which the organism would be worse off, however the
In summary, epigenetic effects exist that are not organism has to pay a price for the benefit. The benefit
necessarily adaptive, and in many of these cases, the derived from a given response depends on the circum-
inherited phenotype is actually detrimental to the organ- stances and the conditions where it occurs. As recently
ism. Environmental exposure to nutritional, chemical, pointed out (Young and Marchini, 1990), every adap-
and physical factors can alter gene expression and affect tation involves a choice. For example, a man has
adult phenotype: a process known as epigenetics. In all 6 hours in which to walk 11 km. If he walks slowly,
of these studies, the extent of DNA methylation depends he saves energy expenditure, and therefore it may be
on and is inversely related to the developmental state of adaptive if the energy resources are limited; however
he has no time left to do anything else. On the other 7. Compare developmental and adult adaptation.
hand, if he walks fast, he saves time at the cost of using Which is more likely to be reversible and why?
more energy. Thus, the adaptive importance of given 8. Discuss the applicability of the concept of develop-
type of response depends on the conditions. mental adaptation to the hypothesis thrifty geno-
The concept of developmental adaptation has type and thrifty phenotype that account for the
become a major focus for studying the origins of human increased frequency of the adult metabolic syn-
diversity (Figure 2.2). The applicability of this research drome among native and nonnative populations.
strategy is based upon the premise that human biological 9. Discuss the relationship of the concept of develop-
responses to environmental stress represent a continu- mental adaptation to the field of epigenetics.
ous process whereby past adaptations are modified and
developed to permit the organism to function and main-
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3 History of the Study of Human Biology
Michael A. Little
INTRODUCTION biology will be traced through the contributions of

key authors, their ideas, and the role of key institutions
The field of human biology is broad based but with its in its history.
principal origins in studies of variation in living popu-
lations within physical or biological anthropology.
Today, human biology incorporates a majority of sci- RACE AND TYPOLOGY
entists trained in anthropology, but also counts among
its members scientists trained in other specialties of The tangled roots of interests in human biology and
the human sciences. During the late nineteenth and human variation lie deep in antiquity. In the early
early twentieth centuries, our stem science – physical modern era, Europeans became acutely aware of human
anthropology – was oriented toward skeletal studies, population variation during the Age of Exploration and
gross anatomy, and human variation as represented by the opening of new regions of the world in the fifteenth,
race. Skeletal studies included those of both living and sixteenth, and seventeenth centuries (Eiseley, 1958).
prehistoric populations. Anatomically oriented studies Newly discovered populations from the Americas,
of the skeleton and of the living were focused on struc- Africa, the Pacific, and Asia, were classified, along with
ture and origins, but with less interest in function and Europeans, into broad racial groups according to phys-
evolutionary causality. In the his Manual of Physical ical characteristics. Such racially based physical charac-
Anthropology, Juan Comas (1960) presented an excel- teristics were erroneously thought to be tightly bound to
lent overview of the history of physical anthropology mental, emotional, intellectual, and cultural attributes,
from its earliest origins, including the origins of and as well. Some races were identified as clearly inferior to
connections with natural history, racial classification, others on a typological scale – an extension of The Scale
craniometry, prehistory and paleoanthopology, and of Being – from primitive to advanced. Ideas of fixed,
evolution. In later chapters, he reviewed the histories unchanging racial categories were tightly bound to
of growth studies, somatology, constitutional typology, Judeo-Christian religious beliefs associated with, among
craniology, osteology, and racial classification. other things, the creation or origin of humans. Some
The beginning of an integrated human biology in believed that humans originated from a single creation,
the United States dates back to the late 1920s when monogenism, where the more primitive races had then
Darwin’s ideas of population variation, adaptation, degenerated from the original people living in the
selection, and evolution began to be reconceptualized Garden of Eden. Another belief was in polygenism, where
by a number of leading scientists. At that time, evolu- God had created several independent peoples, some who
tionary theory, and concepts from behavioral sciences, were elevated to civilization and others doomed at
demography, genetics, and child growth began to be the outset to perpetual savagery. In both of these beliefs
consolidated into a science of human biology. In later of human creation, Western, civilized populations
decades, body composition, physiology, nutrition, and were held, with a few exceptions, to be superior to non-
ecology were added to the mix leading to an even Western races from Asia, Africa, the New World, and the
greater understanding of the variations in, the evolu- Pacific.
tion of, and the characteristics of humans in all of their Within Western societies, the two sexes were con-
complex biobehavioral states. sidered unequal – men were believed to be superior to
A history of anything is a reflection of traditions, women, by virtue of their very nature, and women were
connections, and innovations. These can be found as often viewed as incapable of rational thought (Stocking,
well in a history of human biology. In the narrative that 1987). Women were more emotional than men and tied
follows, the development of the science of human more closely to nature through their role in reproduction
29
30 Michael A. Little
and childbirth. The upper socioeconomic classes were and the first chapter by Mielke et al. (2006) provide
believed to be innately superior to the lower classes, histories of these controversies about race. Fundamen-
because class differences were thought to have a heredi- tally, all classifications of this nature are essentialist in
tary basis. Hence, aristocratic males (“good breeding”) character, that is, they focus on fixed types that obscure
were alleged to be at the pinnacle of God’s creations. the variation that contributes to human population diver-
There were some who questioned the dominance of sity around the globe. It was the rejection of typological
nature over nurture, however. For example, in the last thinking (fixed species and races) that enabled Darwin to
chapter of the popularly known Voyage of the Beagle conceptualize ideas of variation, adaptation, and natural
(Darwin, 1839), a thoughtful Charles Darwin noted, in selection (Mayr, 1972), and it was this same transition in
the context of slavery: “. . . if the misery of the poor be thinking about human populations that moved human
caused not by the laws of nature, but by our institutions, biologists toward a truly scientific approach in this field.
great is our sin . . .” (Darwin, 1839, p. 433). Questions
about the contributions of nature (heredity) and nurture
(environment) to human diversity persist and are
FRANZ BOAS AND HIS CONTRIBUTIONS
debated up to the present.
Eighteenth-century racial classifications were
Although the late nineteenth and early twentieth
established by Carolus Linnaeus (1707–1778), Georges
centuries were characterized by beliefs in fixed racial
Louis Leclerc, the Comte de Buffon (1707–1788),
types, accompanied by beliefs in the superiority of
Georges Cuvier (1769–1832), and, of course, Johann
some racial groups over others (racism or racialism),
Friedrich Blumenbach (1752–1840) (Gould, 1996;
there was a contrary opinion in the form of Franz
Molnar, 2002). Classifications ranged from Linnaeus’s
Boas (1858–1942). Boas, often referred to as the
Asian, European, African, and American groups to
founder of American anthropology and the four-field
Blumenbach’s Caucasian, Mongolian, Ethiopian,
approach, made remarkable contributions to dispel-
American, and Malayan.
ling the myth of fixed or pure races and the importance
Twentieth-century classifications of human popula-
of the environment in structuring the character of
tions have been devised in numerous combinations
human populations (Figure 3.1). These interests in
and have been based on a variety of criteria. Earnest
human plasticity in the context of race were almost
A. Hooton (1931), the Harvard professor who trained
certainly based on his research on child and adolescent
most of the modern generation of physical anthropolo-
growth and development (Tanner, 1959, 1981). Hence,
gists before World War II, identified “composite races,”
he can be identified also as one of the founders
in addition to the “primary races and subraces.”
of human biology in the United States because of
The composite races were formed by admixture of
his contributions to: (1) debunking the idea of fixed
primary races. Carleton Coon was one of Hooton’s early
races; (2) establishing a migration research design that
students who had written a book classifying The Races of
Europe (Coon, 1939). Several years later, Coon et al.
(1950), in a mid-twentieth century approach, presented
a six-fold geographical classification and then divided
these major races into thirty subpopulations, whose char-
acteristics were based on external physical and skull attri-
butes. In that same year, Boyd (1950) identified six races
according to their blood group genetics. About a decade
later, Garn (1961), who was a coauthor of the Coon et al.
(1950) book, refined these classifications and identified
geographical, local, and micro-races, in a hierarchy of
populations and subpopulations. These three works were
different from previous efforts at classification in that
they attempted to apply contemporary evolutionary,
genetic, and ecological principles to the identification of
racial (population) variation around the world. They were
transitional in the sense that they applied modern
theory to an outdated typological system in which bound-
aries between populations were fixed. There has been
considerable controversy in scientific writings over the
intervening years about the utility and social impact of
racial classification and the validity of the concept itself. 3.1. Franz Boas (1858–1942) in 1906. Photograph with permis-
Works by Shipman (1994), Marks (1995), Brace (2005) sion from the American Philosophical Society.
History of the Study of Human Biology 31
continues to be used up to the present; (3) incorpor- acknowledged the plasticity in the immigration study
ating the social and material environment as influen- when he stated: “These changes do not obliterate the
cing human biology (plasticity); and (4) making differences between genetic types [characters] but they
numerous discoveries about the patterns of growth in show that the type as we see it contains elements that are
children and adolescents. not genetic but an expression of the influence of the
The migrant study, designed to test the idea of races environment” (Boas, 1936, p. 523).
as static types, was initiated in 1908 with modest funding Boas growth studies date back to 1888 when
from the US Immigration Commission. The pilot study he took an academic position at Clark University in
began in June 1908 with studies of height and cephalic Worcester, Massachusetts. His first important discov-
index of Eastern European Jewish boys in New York ery was based on data gathered by the growth studies
City Schools (Stocking, 1974). The results of the pilot pioneer and Harvard professor, Henry Bowditch
study and the more extensive study of Bohemians, (Tanner, 1959). Boas discovered that the asymmetrical
Sicilians, Neapolitans, Polish, Hungarians, and Scots distributions in Bowditch’s data on height during
established differences between those born to parents adolescence could be explained by the individual
before and those born to parents after they migrated to variations in growth rates, which he called “tempo of
the United States (Tanner, 1959). Head form or cephalic growth.” This is the first indication of Boas’s sensitivity
index differed between the two groups, refuting the idea to the importance of longitudinal growth data in
of fixed races and demonstrating the influence of the uncovering subtle changes in growth during childhood
environment on human variation in physical characteris- and adolescence. In 1891, he initiated a longitudinal
tics. The completed study, published by Boas (1912), was survey of Worcester school children that confirmed his
accompanied by the publication several years later of the sense of the value of longitudinal growth data. Between
raw data of more than 18 000 subjects who were meas- 1892 and 1941, Boas published numerous papers on
ured in the migration study (Boas, 1928). The reanalysis growth in Science, Human Biology, and other journals
of these data stimulated a new controversy (Sparks and in which he made other significant discoveries, each a
Jantz, 2002; Gravlee et al., 2003) over Boas’s analyses and reflection of his remarkable knowledge of statistics and
interpretations and whether he really demonstrated his genius. Over the years, he: (1) produced the first
plasticity in these migrant populations. National Growth Standards or norms; (2) introduced
Relethford (2004), in exploring this controversy, the concept of physiological or developmental age and
identified three ways that craniometric variation can observations that males were behind females as early
change over time: (1) developmental plasticity through as five years of age; (3) observed that working class and
environmental change; (2) long-term changes through poor children from large sibships tend to be smaller on
natural selection; and (3) within-group and among- average than those from small sibships; (4) established
groups variation by gene flow. Each of these has been relationships between “age of peak velocity” during ado-
shown to operate, but what Relethford (2004) noted was lescence and other measures of size during adolescence
that the debate about Boas’s study centered on the rela- and adulthood; and (5) observed that children from the
tive importance of these three causes of craniometric Horace Mann School of Columbia University had
change. Based on the two major studies, the question become larger between 1909 and 1935 (now known as
that Relethford raised, “. . . is whether developmental the secular trend in growth) (Tanner, 1959, 1981).
plasticity has a significant effect on craniometric vari-
ation” (Relethford (2004, p. 380). Relethford approached
this question by inspecting the changes in craniometric PRE-WORLD WAR II AND HUMAN
variation among the groups Boas studied. Three of the POPULATION BIOLOGY
seven European ethnic groups showed no statistical dif-
ference between US-born and European-born migrants In addition to Boas’s contributions to a developing field
(Hungarians, Polish, and Scots). The remaining four of human biology through his growth studies, there are
groups did show statistically significant differences, but several other lines of continuity from pre-World War II
these were relatively slight differences. Based on this, to the present. In 1929, Raymond Pearl (1879–1940)
Relethford (2004) suggested that these data do demon- founded the journal Human Biology and served as editor
strate developmental plasticity, but this plasticity does until his death in 1940 (Crawford, 2004). Pearl was an
not obscure the underlying genetic differences that accomplished population biologist who was Professor
separate the ethnic groups. In other words, both genetic of Biometry and Vital Statistics in the School of Hygiene
characters and developmental plasticity contribute to and Public at Health at Johns Hopkins University and
the variation, but the genetic contribution to the total who had broad interests in genetics, fertility, evolution,
variation, in this case, is the stronger of the two. Releth- nutrition, disease, duration of life, senescence, and
ford’s (2004) conclusion was anticipated by Boas in a physical anthropology (Figure 3.2). According to Kings-
paper published years after the original, where Boas land (1984, p. 8), “Pearl considered himself to be first
was editor in the 1930s. It is probably the case that

Aleš Hrdlička, one of the founders and first president of
the AAPA, and Pearl did not share the same scientific
philosophy because of Hrdlička’s strong dislike and
avoidance of statistics and Pearl’s commitment to their
use (Lasker, 1989). This added an additional dimension
to the differences between the AJPA and HB, since
Hrdlička was editor of the former and Pearl was editor
of the latter.
Perhaps the most extensive pre-war research in
human biology was that of human growth conducted
at several centers in the United States. Some of these
longitudinal growth studies (sequential measurements
over time of the same individuals) were the Fels Longi-
tudinal Study (Yellow Springs Ohio), the Bolton-Brush
Study at Western Reserve University (Cleveland, Ohio),
the Berkeley Growth Study at the Institute of Human
Development, University of California (Berkeley), the
Child Research Council Study at the University of
Colorado (Denver), and the Harvard School of Public
3.2. Raymond Pearl (1879–1940) sometime in the late 1920s or Health Growth Study (Boston) (Roche, 1992, pp. 1–2).
early 1930s. Photograph with permission from the American
Each of these was founded from the 1920s to the early
Philosophical Society.
1930s principally to determine the effects of the Great
Depression and to assess the means to help impover-
and foremost a human biologist”; that is, he was totally ished children. As Tanner noted: these longitudinal
committed to a human population biology that was studies were part of “. . . a powerful child welfare move-
quite akin to some of the holistic and integrated science ment [that] arose in the 1920s and provided the soil for
practiced today. a crop of longitudinal studies, whose harvesting
The journal, Human Biology, published a variety of shaped the whole pattern of human auxology in the
papers in, among other topics, genetics, growth, health, years 1935–1955” (Tanner (1981, p. 299). Here he uses
human population studies, mathematical and statistical the term auxology, which refers to the study of human
modeling, and human evolution. Goldstein (1940), in a physical growth, which he (James Tanner) pioneered
survey of the first decade of Human Biology (HB) and two in the 1950s and 1960s in the United Kingdom
decades (1920s and 1930s) of the American Journal of (Figure 3.3). It is not clear to what extent Boas’s work
Physical Anthropology (AJPA), suggested that the journal
HB published articles more in the realm of “biological
anthropology” whereas the AJPA was more prone to
publish in “anatomical anthropology.” These patterns of
topical publication imply that the earliest development
of a professional human biology “identity” began about
this time. As Goldstein (1940) reported, there were strong
connections between Pearl and his journal and physical
anthropology – connections with the journal that have
continued to the present. Many early papers in Human
Biology were published on topics related to physical
anthropology (Lasker, 1989). Raymond Pearl and Franz
Boas were acquainted at that time because Pearl was
active in a number of professional societies in which Boas
was a member, including the American Association of
Physical Anthropologists (AAPA). In fact Pearl was well
known among physical anthropologists of this time as
evidenced by his election as the third president of the
AAPA from 1934 to 1936. Moreover, both Pearl and Boas
were members of the National Academy of Sciences, both
were sophisticated biostatisticians, and Boas published 3.3. James M. Tanner (1920–) at a conference in 1982. Photo-
several papers on growth in the journal HB while Pearl graph courtesy of Barbara Garn.
stimulated these longitudinal growth studies, but himself in studies of body composition. The study began
principle investigators must have known the value of in 1944 with 36 conscientious objectors who volunteered
longitudinal series from Boas work before the turn for the full-year study that consisted of an equilibration
of the twentieth century and later papers in the 1930s. period on a normal diet, 3 months of semi-starvation
For example, when Frank Shuttleworth (1889–1958) (1600 kcal/day), and a period of refeeding. In addition,
analyzed the Harvard Growth Study data, he employed the volunteers were expected to walk 22 miles per week
some of the same procedures that Boas employed in to increase their energy expenditure. The study was
analyzing data of adolescent girls (Tanner, 1981, p. 310). intensive, with almost daily biochemical, physiological,
Boas’s influence was also seen in students from psychological, and body composition measurements
Harvard and elsewhere who used his migration model taken. The result of the study were published in two
in their own research during the 1930s and 1940s massive volumes that stand as state-of-the-art research
(Little and Leslie, 1993). For example, Harry Shapiro even today, particularly since it probably would not be
and Frederick Hulse (1939) studied Japanese migrants permitted to conduct such a high-risk project during
to Hawai’i, Marcus Goldstein (1943) measured Mexican- present times (Keys et al., 1950).
Americans, and Gabriel Lasker (1946) studied immigrant The Rochester Desert unit was charged with the
and American-born Chinese. The migration-research research task of determining water and food require-
design was also used in a great deal of human biology ments, sweat rates, energy balance, heat tolerance,
research up to the end of the twentieth century. work capacity, and the probability of survival while
living under the hot-dry conditions of desert environ-
ments. Much of the desert research was conducted on
THE WORLD WAR II YEARS military personnel on maneuvers in southern Califor-
nia. Other studies were conducted of men on life rafts
The enormity of World War II brought a halt to a great without water, and some limited tests were conducted
deal of academic research in the United States and under hot-wet conditions in Florida to simulate troops
elsewhere, but stimulated research that could be directly in tropical forests. In the preface to the volume that
applied to the war effort. Some of this research carried reported this research, the authors identify this work
over to the post-war years and not only led to additional as a part of the “. . . recently developing field of environ-
academic research, but even contributed to changes in mental physiology” (Adolph and Associates, 1947,
thinking about the causes of human variation. Much of p. vii). What was not known then was that this work
the wartime research centered on the maintenance and was to stand as the first major work in climatic stress
health of US troops in stressful environments and ameli- physiology, and one that would serve as the basis for
orating the stress of warfare and hunger in the civilian heat-stress studies both in environmental physiology
populations in Europe and Asia. During the war, US and human biology.
military personnel were stationed and fighting in In addition to the pioneering research in nutritional
Europe, East Asia, Southeast Asia, North Africa, the and environmental physiology represented by these
Pacific, and Alaska and the Aleutian Islands. Hence, they two wartime studies, a relatively new area of human
were expected to be able to work strenuously at high variation was being developed that would be explored
levels while at the same time being exposed to climatic by anthropologists and human biologists interested in
variation that ranged from Arctic and temperate zone growth, environmental stress, exercise physiology, and
winter cold to tropical and temperate summer heat. nutrition – body composition. These early studies intro-
In addition to stresses from dietary restriction and star- duced hard-tissue anthropologists (bone and teeth) to
vation and from climatic extremes, there was interest in the importance of soft tissue (muscle and adipose tissue)
the interaction between diet and climate, particularly in human function, human growth, and in studies of
in the context of providing enough food calories for human adaptation to the environment.
troops fighting in cold or hot geographic zones (Mitchell
and Edman, 1951). Two of the most prominent wartime
studies will be surveyed briefly: the semi-starvation POST-WAR UNITED STATES AND
study conducted at the University of Minnesota and the UNITED KINGDOM
desert physiology study conducted by the Rochester
Desert Unit whose research was conducted at several There were parallel transformations of physical anthro-
places in the United States. pology in the years directly following World War II in
The Minnesota semi-starvation study was initiated by both the United States and in the United Kingdom.
Ancel Keys (1904–2004), a stress physiologist best known In the United States, Sherwood L. Washburn (1911–
for having developed K-rations during the early part of 2000) successfully promoted a scientific agenda of prob-
the war, and several colleagues including Josef Brožek lem solving, application of evolutionary theory, and
(1913–2004), a psychologist who later distinguished understanding of human variation rather than racial
the 15th Cold Spring Harbor Symposium on Quantitative

Biology (Warren, 1951) and was initiated by the Cold
Spring Harbor Institute Director, Milislav Demerec
(1895–1966). Washburn’s co-organizer of the Sympo-
sium, called “Origin and Evolution of Man,” was the
distinguished geneticist, Theodosius Dobzhansky
(1900–1975), whom he had met at Columbia University.
Although the conference was successful in bringing
together geneticists, evolutionists, and anthropologists,
there were some differences among the more traditional
physical anthropologists, particularly the typological
“constitutionalists” such as William Sheldon and
Earnest Hooton on the one hand, and the more for-
ward-looking physical anthropologists and geneticists
on the other concerning topics of race and population
variation. “Constitutional somatology” is an outmoded
and typological area of study of body form and associated
behavior that has a long history (see Comas, 1960, 319 ff.)
and was promoted by Sheldon (Sheldon et al., 1940)
3.4. Sherwood L. Washburn (1911–2000) at the 1952 Wenner- and Hooton (1939) at the Cold Spring Harbor meeting.
Gren Foundation International Symposium of Anthropology. Many years later, the daughter of the Institute Director,
Photograph courtesy of the Wenner-Gren Foundation for
Rada Dyson-Hudson, who had attended the Symposium
Anthropological Research.
as a young Swarthmore College student, remarked that
after the afternoon sessions, the geneticists would
typology and simply descriptive anthropometric survey gather to discuss the talks given that day, while the
(Washburn, 1951). Washburn, who had been trained at anthropologists would head for the nearest local tavern!
Harvard, among many others, under Earnest A. Hooton Despite these differences, new ground had been broken,
(1887–1954), rejected many of the traditional ideas of his and Washburn’s “scientific and evolutionary” physical
mentor and began an active program to bring his new anthropology was gaining momentum.
ideas to other anthropologists, especially younger ones In the United Kingdom, the transformation also
(Figure 3.4). With support from a private anthropological involved experimental scientific approaches to investi-
foundation in 1946, he organized the Viking Fund gating human variation and the application of evolu-
Summer Seminars in Physical Anthropology. These tionary theory as a basis for explaining human
Summer Seminars were dynamic “state-of-the-art” meet- variation. The United Kingdom’s transformation
ings in which many new ideas in physical anthropology moved in two directions: first, toward an adaptive
were explored for the first time. Washburn, despite and ecological view of human biological function, and
having received his PhD degree only six years earlier second toward an evolutionary view of human genetic
(1940), already was a dynamic force in the field of population structure. The leaders in this movement
physical anthropology. He was Secretary-Treasurer were Joseph S. Weiner (1915–1982) and his colleague
of the AAPA (1943–1946), had been teaching anatomy at Nigel A. Barnicot (1914–1975) (Harrison, 1982). Weiner,
Columbia University since 1939, and persuaded Paul who was trained in physiology, anatomy, and anthropol-
Fejos (1897–1963), Director of the Viking Fund (later the ogy in South Africa, came to England in 1937. With post-
Wenner-Gren Foundation), to sponsor these Summer war academic posts at Oxford with the distinguished
Seminars held in New York City. In addition, Washburn anatomist Le Gros Clark, and later at the London
enlisted a new Harvard PhD, Gabriel W. Lasker School of Hygiene and Tropical Medicine, he contrib-
(1912–2002) to edit a new Yearbook of Physical Anthro- uted to the training of a whole generation of human
pology to report on the Summer Seminars and other news biologists, promoted the transformation of physical
of the profession as well as to reprint important papers anthropology, and was instrumental in organizing
not easily found in American anthropology journals. and managing human adaptability research during the
The Yearbook of Physical Anthropology has continued to International Biological Programme (IBP) from 1962 to
the present from the year of its first publication in 1946. 1974 (Harrison and Collins, 1982). Barnicot was trained
In 1950, the fifth year of the Summer Seminars, in zoology and physiology, and was in the Anthropology
Washburn organized a major conference that served Department at University College, London for most
to bring together physical anthropologists and human of his professional life. He worked on blood genetics,
geneticists with hopes to produce a fresh synthesis and skin and hair color in West African populations, on
in human variation and evolution. The conference was studies of nonhuman primates and, in later years, on the
human biology of Tanzanian Hadza hunter-gatherers

(Sunderland, 1975).
Joseph Weiner was also a strong supporter of
biocultural approaches in human biology, in addition
to his commitment to solid experimental studies in
human physiology. In a 1958 paper on “. . . training in
physical anthropology and human biology,” he noted,
“. . . it should be emphasized that in their [students’]
research interests an important field of overlap
exists between biological and cultural anthropologists”
(Weiner, 1958, p. 47). Shortly before his death and nearly
25 years after the earlier statement, Weiner wrote:
The simple fact that his unit of study is a defined community
has made it imperative for the human biologist to take full
account of the sociocultural properties of his community.
Population structural analysis . . . cannot be pursued without
close attention to social factors whatever parameter is under
examination. Genetic analysis is inseparable from
demographic and mating patterns; nutrition and energetics 3.5. Gabriel W. Lasker (1912–2002) at his desk. Photograph
are inseparable from food production and food distribution, courtesy of Bernice A. Kaplan.
and land holding; climatic adaptation must encompass the
technology of housing and clothing; biomedical fitness is
related to population size, sanitary systems, health services
(1945) on Chinese migrants; James N. Spuhler (1946)
and life-style (Weiner, 1982, p. 19).
on human genetics; Stanley M. Garn (1948) on human
Several other leading human biologists in the United hair composition and distribution; William S. Laughlin
Kingdom who were junior to Weiner and influenced (1949) on Aleut populations; Edward E. Hunt, Jr (1951)
by his ideas maintained this biocultural perspective. They on Micronesian populations; and Paul T. Baker (1956) on
are Geoffrey A. Harrison, Derek F. Roberts, and James M. desert-heat stress. With the exception of Alice Brues and
Tanner. Roberts conducted pioneering demographic and Paul Baker, all of these young anthropologists attended
genetic research on Southern Sudan peoples (Roberts, some or most of the six Summer Seminars organized by
1956). Harrison and Tanner, along with Barnicot and Washburn that were held in New York City, and many
Weiner, wrote the first modern textbook in Human contributed directly to these sessions, as well. Gabriel
Biology in 1964, that continued the British tradition of Lasker’s (1999) memoir describes some of his associ-
anthropological and biocultural perspectives in human ations with Hooton’s students at this time.
biology (Harrison et al., 1964). In each section of the Again, in parallel with the United Kingdom, Ameri-
book, culture figured prominently in examples that were cans Gabriel W. Lasker and Paul T. Baker provided
presented. Overseas field experience and a commitment inspiration and guidance to junior colleagues and
to comparative studies were attributes that exemplified students by promoting a biocultural framework. As
most of this generation of biomedically trained human noted, Lasker (Figure 3.5) had built on Boas’s migration
biologists. Each of these attributes led to an appreciation model in studies of Chinese (Lasker, 1946) and Mexican
of the need to study human biology in the context of (Lasker, 1952) migrants. In addition to his research,
human behavior and culture. which he pursued actively for more than 50 years, a
In the United States, with the stimulus of Washburn’s major and long-term contribution to students and
ideas on science and evolution, Earnest Hooton’s former junior colleagues was by way of support of their papers
students at Harvard were moving the human biology submitted to the journal Human Biology, which he
of living populations forward. Washburn contributed edited for 35 years. Baker (Figure 3.6), published widely
very little to the growth of human biology because his with his own strong biocultural commitment, and also
interests were largely in skeletal biology, functional socialized his students about the value of biocultural
morphology, and primatology. Hooton’s students, who research. In a paper published four and a half decades
completed their PhDs between 1940 and 1956, were to ago on “Climate, culture, and evolution,” he stated:
become the leaders in human biology during the next “To completely reject the concept of climatic selection
generation. These included, with PhD year in paren- without cultural involvement would be premature, but
thesis: Alice Brues (1940) on the genetics of eye, skin, from anthropology’s present theoretical framework it is
and hair; Marshall T. Newman (1941) on the peopling of more accurate always to consider the role of culture
the American Southeast; Joseph B. Birdsell (1942) on when trying to formulate an evolutionary process
Australian Aborigine populations; Gabriel W. Lasker related to climate” (Baker, 1960, p. 5). Twenty years later
AFTER THE MIDDLE OF THE TWENTIETH

CENTURY
After 1950, new directions were taken in climatic morph-

ology and physiology, genetics, disease, and adaptation
to the environment. The book by Coon et al. (1950)
outlined applications to climatic rules in humans includ-
ing Bergmann’s rule (body size) and Allen’s rule
(size and shape of extremities), and may have stimulated
several biogeographic studies of human form. For
example, Derek F. Roberts (1952, 1953) from the United
Kingdom and Eugene Schreider (1950, 1951) from
France explored relationships between body size and
basal metabolism and climate in human populations
around the world. They found that humans, as with
other warm-blooded animals, conformed to Allen’s and
3.6. Paul T. Baker (1927–2007) (left) and Stanley M. Garn Bergmann’s rules. Other anthropologists from both
(1922–2007) (right) some time during the late 1950s or early sides of the Atlantic conducted similar studies of the
1960s. Photograph courtesy of Barbara Garn.
climatic environment and adaptation of humans to
both heat and cold stress (Newman, 1953, 1956; Weiner,
Baker (1982) continued to emphasize this theme 1954; Newman and Munro, 1955; Baker and Daniels,
about the importance of the linkage between human 1956; Baker, 1958a, 1958b). Some of these studies were
biology and culture in a Huxley Memorial Lecture. experimental (either laboratory or field) and were influ-
In his 1996 Pearl Memorial Lecture, he summarized enced by the physiological studies conducted of heat and
his ideas and underlined the “. . . need for all human cold stress of South Africans (Wyndham et al., 1952),
biologists to have some training in relevant aspects Australian Aborigines (Scholander et al., 1958), Arctic
of cultural anthropology” (Baker, 1997). Such a pers- Indians (Irving et al., 1960), Inuit/Eskimos (Brown and
pective seemed not only intuitively correct and Page, 1952; Meehan, 1955), Alakaluf Indians (Hammel,
logical to Baker, but it also led to more productive 1960), and Laplanders (Scholander et al., 1957). These
lines of research and testable hypotheses. Weiss and and other studies demonstrated quite clearly that
Chakraborty (1982, p. 383) observed that the complex human populations distributed around the world had
influence of culture on evolution “. . . is a point still adapted morphologically, physiologically, and behavior-
largely misunderstood or ignored by many researchers ally to the climatic conditions of their environments.
without anthropological training.” Harrison (1982, The difference between the physiologists’ studies and
p. 471) suggested that it is much easier to give “equal the anthropologists’ studies was in the anthropologists’
attention . . . to cultural as to biological . . .” processes in understanding of the role of culture in these patterns of
the United States than in Europe, because the subfields adaptation to temperature extremes (Baker, 1960). The
of anthropology can often be found in the same depart- anthropologists were more concerned with the whole
ment in the United States. culture/population and variations in responses by age
Human biology research and student training and sex, whereas the physiologists’ contributions were
during the immediate post-war years was supported more focused on physiological mechanisms in small
enormously by the private Wenner-Gren Foundation samples of men tested under controlled laboratory
for Anthropological Research (founded as The Viking conditions. Both kinds of studies enriched what we
Fund in 1941). Partly because of the close personal learned and were complementary.
relationship between its Director, Paul Fejos, and One of the post-war military institutions that stimu-
Sherwood Washburn, the Foundation supported the lated work in anthropology and human biology was the
Summer Seminars, the Yearbook of Physical Anthropol- Natick, Massachusetts Quartermaster Corps Climatic
ogy, and other activities associated with the develop- Research Laboratory (Francesconi et al., 1986). Being
ment of physical anthropology during that time close to Harvard University it could draw on talented
(Szathmáry, 1991). During these early years, and up individuals from this university and also influence
to the present, it is hard to imagine how human biol- research directions there and elsewhere, as well. Many
ogy, within the larger field of physical anthropology, of the young scientists at the Climate Research Labora-
could have developed into a mature science without tory were environmental physiologists who became
the vision of Paul Fejos and later directors of the well-known scientists in later years, while a few of the
Wenner-Gren and the financial support of the Founda- scientists were trained in physical anthropology
tion (Baker and Eveleth, 1982). (e.g., Paul Baker and Russell Newman). Since the
Natick laboratories were also engaged in clothing and research in the anthropology department. Another
nutrition studies, there were also strong interests in major contribution in human genetics in the 1950s was
body size (anthropometry) and body composition vari- Livingstone’s (1958) paper on the anthropology of sickle
ations in military personnel. These government studies cell in West Africa. Based on fieldwork in Liberia and
contributed to the mix of interests in nutrition, disease, extensive literature research on West Africa, he demon-
body composition, and climate in the context of human strated the relationships among malaria, sickle cell
adaptation to variable environments. distribution, mosquito ecology, agriculture (forest trans-
By the early 1960s, studies of body composition in formation), and language and human migration. Only
human biology were on the rise (Brožek and Henschel, four years after Allison’s (1954) publication, Livingstone
1961; Brožek, 1963; Garn, 1963). Interests among had shown the importance of culture in structuring
anthropologists were derived, in part, from knowledge evolutionary change through its influence on malaria
of skeletal biology and were linked closely to studies of prevalence and gene-frequency distributions. Culture
nutritional adaptation (Brožek, 1956; Newman, 1960, change had produced evolutionary change!
1962), and child growth (Garn and Shamir, 1958). Other important genetics work in the 1950s and 1960s
Anthropometric (Garn, 1962) and physique (Brožek, by anthropologists outside the United States and the
1956) surveys were carried out to evaluate nutritional United Kingdom included research by Jean Hiernaux
status, and associations between growth and nutrition in (1966), from Paris, who studied blood-group genetics in
stressful environments were studied (Roberts, 1960; African populations. Another major figure is Francisco
Schraer and Newman, 1958). Josef Brožek (1999) Salzano (Salzano and Callegari-Jacques, 1988), from
provided a personal history of body composition studies Brazil, who first did post-doctoral research with James
in human biology. Neel at the University of Michigan in the late 1950s, and
During this period, human population genetics who went on to become the major human geneticist to
focused almost exclusively on blood polymorphisms. study tropical forest Native Americans in South America.
A good example was Alice Brues’s (1954) important
paper demonstrating that selection must have operated
on the ABO blood group system because of the nonran- HUMAN ADAPTABILITY, ECOLOGY, AND
dom distribution of ABO allele frequencies around INTERNATIONAL PROGRAMS
the world. Electrophoresis was first used to separate
proteins, and it was at this time that “. . . the staggering Among human biologists, the 1960s ushered in a
magnitude of [human] genetic variation . . .” became mature sense of scientific problem solving, an increasing
apparent (Cavalli-Sforza et al., 1994, p. 3). One of the commitment to understanding evolutionary process
great discoveries of the 1950s was the relationship and adaptation to the environment, and a growing inter-
between the sickle cell gene and malaria and the protec- est in integrated, collaborative studies. In anthropology,
tion afforded against malaria by the sickle cell heterozy- broadly, there was a movement toward empiricism
gote. James Neel (1915–2000) had worked out the with interests in ecological approaches and cultural
genetics of sickle cell disease (Neel, 1949), and then materialism. At the same time, human biologists were
described the anemias of sickle cell disease and thalas- exploring ecological models in the context of adaptation
semia in his 15th Cold Spring Harbor Symposium paper to the environment (Baker, 1962; Little, 1982). In 1964,
(Neel, 1951). Neel proposed mutation or selection as four distinguished British human biologists published
hypotheses to explain the high prevalence of these the first edition of an important introductory textbook
dangerous anemias in the Mediterranean and in Africa, (Harrison et al., 1964). In this book, Geoffrey A. Harrison
but it remained for Anthony Allison to show that and Nigel A. Barnicot dealt with genetics and phenotypic
the major force was natural selection. Allison (1954) variation, James M. Tanner covered human growth, and
demonstrated that the sickle cell gene was a balanced Joseph S. Weiner wrote the sections on human adapta-
polymorphism maintained by the selective pressure of tion and human ecology. This was an important work
malaria. He described in some detail the history of his because it defined the field of human biology, was
early work and the conditions surrounding the discovery synthetic, and it was state of the science for the 1960s.
in an autobiographical paper (Allison, 2002). Weiner’s final section on “Human Ecology” was the first
James Neel established the first human genetics definition of this important perspective in human
department at the University of Michigan in 1956. biology: topics included nutrition, disease, climate, and
At that time, this program was one of the strongest in population (demography), and a central emphasis of the
the country, partly because of its connection with work was on “ecological adaptive processes.”
anthropology. William J. Schull worked with Neel in Two other important events took place in 1964.
human genetics and had a joint appointment in anthro- Firstly, the International Council of Scientific Unions
pology, while James N. Spuhler (1917–1992) and Frank (ICSU) (now the International Council for Science) in
B. Livingstone (1928–2005) were conducting genetic Paris established the International Biological Program
(IBP) with a planning phase from 1964–1967, a DeVore, 1976) and the Andean Biocultural Studies
research phase from 1967–1972, and a synthesis initiated in 1962 (IBP affiliated, Baker and Little, 1976).
phase to follow from1972–1974. The orientation of this Two other important IBP projects included the
worldwide program was ecological, and its theme was International Studies of Circumpolar Peoples, a four-
“The Biological Basis of Productivity and Human nation investigation of the health of Inuit/Eskimos in
Welfare.” A number of sections of the IBP were designed Alaska, Canada, and Greenland (Milan, 1980), Popula-
to cover various components of ecology and ecosystems tion Genetics of the American Indian, a project that
studies. A separate section called Human Adaptability focused on the Yanomama horticulturalists from Brazil
(HA) was to cover “the ecology of mankind” from a and Venezuela (Neel et al., 1977), and the Solomon
variety of perspectives including health and welfare, Islands Project, organized by Albert Damon and others
environmental physiology, population genetics, child at Harvard (Damon, 1974; Howells 1987). These and
growth, anthropology, and demography (Weiner, 1965). other HA projects were discussed in detail by Hanna
Secondly, although some preliminary preparation had et al. (1972) and from theoretical perspectives by
begun in 1962, an important HA planning conference Lasker (1969).
was held in Austria at the Wenner-Gren Foundation Burg Other major contributions from the IBP were the
Wartenstein Conference Center in the July of that year. surveys of human growth (Eveleth and Tanner, 1976)
It was at that meeting that Weiner (1966) outlined the and human gene frequencies (Collins and Weiner,
major categories of planned research, and the other, 1977) that were conducted on populations around the
more than 20 internationally represented, participants globe that contributed primary data. In many of these
reported on current knowledge over a wide variety of smaller Third World projects, research design and
topics in human biology for North and South American, “problem orientation” were subordinated to data
European, Asian, African, and Australian populations collection, but these important data sets, then, became
(Baker and Weiner, 1966). Weiner, who was Inter- available for comparative, historical, and in-depth
national Convener (director) of the Human Adaptability analyses for future investigators (Weiner, 1977).
Section of the IBP prepared a handbook (Weiner and Following the close of the IBP in the 1970s, a new
Lourie, 1969) of standardized methods, and at the end international program arose from UNESCO (United
of the IBP published a compendium of the completed Nations Educational, Scientific, and Cultural Organiza-
research (Collins and Weiner, 1977). The planning and tion) called the Man and the Biosphere Program (MaB).
research that followed resulted in the participation of Additional multidisciplinary projects were affiliated with
40 nations, the completion of more than 230 projects, the MaB program including the Multinational Andean
and several thousand publications under the HA banner. Genetic and Health Project (Schull and Rothhammer,
In a retrospective review of the HA research, there has 1990) and the Samoan Migrant Project (Baker et al.,
been some criticism based on topical omissions, but the 1986). Other projects, such as the South Turkana
contributions far outweigh the shortcomings (Ulijaszek Ecosystem Project (Little and Leslie, 1999), the Ituri
and Huss-Ashmore, 1997). Harrison (1997, p. 25) noted, Forest Project (Bailey, 1991), and the Siberian Evenki
in a contribution to the same review: “Notwithstanding Project (Crawford et al., 1992) followed somewhat later.
its limitations, it played a major part in converting the old These multidisciplinary projects promoted international
defunct physical anthropology into the vibrant and excit- collaboration, gathered fundamental data on popula-
ing component of biological anthropology as it is today.” tions that were on the brink of extinction, were instru-
In addition, it is quite clear that the associations made mental in developing new field and experimental
between the British and American human biologists methods, and provided research training for a whole
during the IBP were of remarkable value by serving to new generation of human biologists.
cross-fertilize ideas and to reinforce the biocultural and
environmental perspectives shared by most of the partici-
pants (Baker, 1988). DNA ANALYSIS AND MOLECULAR GENETICS
One of the major conceptual contributions of the IBP
was in the organization of multidisciplinary research Weiss and Chakraborty (1982) provided a detailed
(Little et al., 1997). Because complex ecosystems required review of the history of human genetics up to the late
broad expertise, many individuals from different fields of 1970s. The late 1970s and 1980s, however, marked a
science were required to collaborate. Ecologists from the dramatic transition in human population genetics
IBP were organized according to major ecosystems (e.g., from a reliance on phenotypic proteins and inference
tropical forests, arctic tundra, deserts, and grasslands), about genes (phenotype-based approach) to the direct
while some of the HA projects focused on single human measures of genes via DNA (the new molecular genet-
populations in special environments. Two early projects ics). This transition was based on the new laboratory
were the Kalahari Research Group to study the !Kung methods that enabled DNA to be extracted and purified
Bushmen initiated in 1963 (not IBP affiliated; Lee and from Blood and other tissues (Crawford, 2000). These
methods included: use of restriction enzymes to clip concern of human population biologists about the HGP
nucleotide segments of DNA (restriction fragment was that it would provide a generic genome; that is, little
length polymorphisms), DNA hybridization, and the or no information would be provided on human genetic
polymerase chain reaction for amplification of DNA. variation in individuals and populations around the
Some of the new DNA methods were used in human world. Such variation was of value to studies of human
biology for phylogenic reconstruction of our ancestors, evolution and population history, as well as applied
to reconstruct human population movements over research in the genetic bases for disease (resistance,
space and time, and for forensic and ancient DNA susceptibility, environmental interactions, etc.) and
analysis. New methods of DNA extraction and analysis genetic epidemiology.
also led to the Human Genome Project and the contro- In response to these concerns, the Human Genome
versial Human Genome Diversity Project. Diversity Project (HGDP) was founded in 1991 under
Mitochondrial DNA (mtDNA), which is only trans- the leadership of L. L. Cavalli-Sforza, the distinguished
mitted through the maternal line and does not undergo Stanford University geneticist. Also, the project was
recombination, has been very useful in a variety of identified as urgent because of the disappearance of
approaches to human evolution (Cann, 1986). One many small Mendelian populations. The proposed
of the most remarkable studies of mtDNA was the HGDP sparked a controversy for a variety of factors:
so-called “Mitochondrial Eve” observation that startled first, there was distrust by anthropologists of the gen-
scientists interested in modern human origins. Cann eticists in their conceptualization of race (linked to
et al. (1987) found in a sample of 147 people from typological race and eugenics); second, there were con-
around the world that “All these mitochondrial DNAs cerns by Native American groups about their being
stem from one woman who is postulated to have exploited again, about race stereotyping, and about
lived about 200 000 years ago, probably in Africa” the potential use of DNA for commercial gain
(Cann et al., 1987, p. 31). This and other DNA work (patenting genes); third, there was an element of polit-
led to the “Out of Africa” hypothesis on modern ical naiveté of the organizing geneticists about conflict-
human origins (Stoneking and Cann, 1989; Vigilant ing beliefs about race and, initially, there were few
et al., 1991). More recent research incorporated the anthropologists included in the program and its design
Y chromosome, which is inherited through paternal (Reardon, 2005). Because of conflicts and protests the
lineages (Hammer, 1995). original plan to establish cell lines of DNA samples
A variety of studies have been conducted to trace from 25 individuals from each of 400 populations was
population distributions and migrations in the historic never satisfied, and funding was not forthcoming.
and prehistoric past. Cavalli-Sforza et al. (1988) and Later the HGDP was revived under the title of HGDP-
Sokal (1988) combined genetic, archaeological, and CEPH (Centre d’Etude du Polymophisme Humain),
linguistic information to reconstruct population and now DNA is available for 1064 individuals from
expansion in Europe. This geographic genetic research 52 populations. These DNA samples have begun to be
continues up to the present (Barbujani, 2000). Another used for research (Ramachandran, 2005).
area of interest that had been dominated by archaeo- During the past half century, there has been
logical evidence soon saw the application of genetic increasing scientific activity in what Derek Roberts
data to the question the peopling of the New World (1965) first referred to as “anthropological genetics.”
(O’Rourke, 2000). Based on mtDNA and Y-chromosome Crawford (2007) outlined the differences between
markers, Merriwether (2002) suggested a single-wave “anthropological genetics” and “human genetics,”
migration, possibly originating from ancient Mongolia where the former incorporates a biocultural perspec-
through Siberia and into the New World between 20 000 tive, focuses on the population and, often, non-Western
and 30 000 BP. All of these dates fall within the late populations, and centers on questions of interest to
Pleistocene when the Wisconsian glaciation covered anthropologists, particularly evolutionary questions.
parts of North America and the cold Beringia land Research in molecular anthropology, genetic epidemi-
bridge between Siberia and Alaska was exposed. ology, forensic anthropology via DNA analysis, human
By the late 1980s, it was feasible to sequence the origins, and the history of human migration and
whole human genome of nucleotides and DNA on the dispersal are all areas of exploration that are being
human chromosomes. This culminated in the Human pursued by anthropological geneticists.
Genome Project (HGP), a massive DNA-sequencing effort
that was estimated to cost several billion dollars. In
the United States, the Department of Energy (DOE) and REPRODUCTION AND CHILD GROWTH
the National Institutes of Health (NIH) supported the
HGP (Crawford, 2000). The work conducted by an inter- Interests in reproduction in anthropology date back to
national consortium began in 1990 and was completed the early part of the twentieth century and are linked
in 2003, several years ahead of schedule. The principal closely to two primary emphases in human biology:
evolution/natural selection and human health. In although energy balance does play an important role.
evolution, differential fertility is one of the main However, Frisch’s research was truly pioneering in that
driving forces of selection, and fertility (measured as it contributed to the development of a new ecology of
number of live-born offspring) is also a prime indicator reproduction that began to explore the evolution and
of adult health and well being. Studies of growth are an ecology of reproductive function in a variety of West-
extension of reproduction and, of course, date back in ern and non-Western peoples (Howell, 1979; Ellison,
human biology to Franz Boas. 1990, 2001; Leslie et al., 1994). These and other investi-
Pioneering studies by Sophie Aberle, who was trained gations explored relationships among nutritional status
in genetics at Stanford and medicine at Yale, were and availability of food resources, disease, physical
conducted of sex and reproduction in San Juan Pueblo activity, endocrine function, body composition, behav-
Indians in New Mexico (Aberle, 1928, 1931). She was a ior, growth, and reproduction – truly an integrated,
member of the National Research Council Committee for behavioral and environmental science of human
Research in Problems of Sex (Aberle, 1953) and worked reproduction.
for the Bureau of Indian Affairs. From her research she At the same time as this new research direction
found that the poor reproductive pattern of Pueblo in fertility and reproduction was being taken, so were
Indians was not based on reduced fertility, which in fact new discoveries being made in infant, child, and adoles-
was very high, but rather was based on extraordinarily cent growth studies. Surveys of the worldwide variation
high infant mortality rates (about 25%). Ashley Montagu in human growth, which were originally compiled from
(1905–1999) conducted early work of female sexual the IBP HA studies, synthesized the available knowledge
maturation by discovering post-menarcheal sterility in on population variations in human growth up to the late
adolescent girls (Ashley-Montagu, 1939a, 1939b, 1946). 1980s (Eveleth and Tanner, 1976, 1990). Somewhat later,
He found that, for a year or more following menarche in Michelle Lampl conducted new longitudinal research of
girls, there was a markedly reduced fecundity or even individual growth patterns (Lampl et al., 1992) in an
sterility, and “. . . that puberty and the power to procreate ingenious study of infant length, where some infants
are not synchronous events . . .” (Ashley-Montagu, 1939b, were measured every day for more than a year. She and
p. 213). The sociologists, Kingsley Davis and Judith Blake her colleagues found that rather than being a continuous
(Davis and Blake 1956) formulated a groundbreaking process as believed, growth proceeded in “incremental
model of factors affecting fertility in the context of bursts” (saltatory growth) followed by periods of stasis.
social behavior. This provided the basis for systematic Some measurements of infants showed daily increases in
hypothesis testing and refinement of the model, which length of up to 1 cm in length! This work was extended
was done by Bongaarts (1978). Campbell and Wood to adolescents, who also showed saltatory growth
(1988) further refined the model for “proximate deter- (Lampl and Johnson, 1993), and has led to new lines
minants” of fertility in non-Western (noncontraceptive) of research in bone and soft tissue growth and in the
as well as Western populations. One of the first studies to endocrine control of growth.
document an important variable, not considered by In the 1980s and 1990s, increasing research in
Davis and Blake (1956), was the central importance growth has been directed toward health and the total
of breast-feeding in fertility control by Konner and life span from conception to senescence and death.
Worthman (1980) in studies of !Kung Bushmen. This This research has had both basic and applied compon-
and other research work stimulated a number of anthro- ents related to health across what has been called the
pological studies of nursing, energetics, and fecundity in “life span approach” to the study of human biology
traditional populations (Bentley, 1985; Gray, 1994; (Leidy, 1996). A general principle of this approach is that
Vitzthum, 1994). “. . . no single stage of a person’s life (childhood, middle
An important series of studies was conducted in the age, old age) can be understood apart from its antece-
1960s and 1970s that explored relationships among dents and consequences” (Riley, 1979, p. 4). Activity
energy balance (diet and activity), body composition levels, diet, and exposure to adverse substances during
(fat and muscle), and reproduction (age of menarche) childhood all influence health during adulthood and sen-
in adolescent girls. The work by Rose Frisch (Frisch escence. It is also the case that longitudinal study of the
and Revelle, 1970; Frisch and McArthur, 1974) led to a same individuals through time, in the tradition of Franz
hypothesis the there was a critical weight, and, then Boas, is one of the best methods to demonstrate these life
later, a critical level of body fat that both triggered span correlations. David J. P. Barker (Barker et al., 1989;
menarche and maintained normal menstrual cycles. Barker, 1992) developed an extension of this approach to
Frisch’s ideas were severely criticized, partly because understanding the life span. He discovered from early
of her unyielding adherence to this basic hypothesis. twentieth-century archival birthweight data that the
Subsequent research has demonstrated that reproduct- lower the birthweights of infants, the greater the risk of
ive controls on the ovarian cycle are more complex coronary heart disease in adulthood. He also found that
than just being a function of the energy of body stores, lower birthweight increases the risk of hypertension,
stroke, and adult diabetes. These findings led to what is (2006) Nobel Prize winning discovery of the Australia
now known as the “fetal origins hypothesis” of adult antigen and hepatitis B virus was carried out while
disease that is currently being explored in a variety of investigators searched for serum protein polymorphisms
research lines today, particularly in the context of juven- in non-Western (anthropological) populations.
ile and adult obesity. Human biologists have also taken advantage of
Another important developing research area in unique opportunities to explore diseases or health threats
human growth focuses on the evolution of the unique in traditional, modernizing, and modern populations
properties of human growth (Bogin, 1997, 1999). (Garruto et al., 1999). The stresses of high altitude
Humans have a unique growth pattern that is similar hypoxia were explored in the Andes (Baker and Little,
to nonhuman primates, but differs to the extent that 1976; Schull and Rothhammer, 1990), and the high
we have a long period of nursing and post-weaning prevalence of amyotrophic lateral sclerosis and
dependence (birth to seven years of age), a period of Parkinsonian dementia in the Chamorros population
rapid growth that defines adolescence, a delayed onset were studied in Guam (Garruto et al., 1989). Of increas-
of reproduction, and menopause in females. These, ing interest in human biology are the effects of modern-
and other unique attributes of human development, ization in non-Western populations, migration from
facilitate development of the brain, manual dexterity, traditional to modern societies, and life-style transitions
and the social and sexual skills needed for life in a in Western populations. For example, the nutritional and
complex society. Evolution of growth has been studied life-style transition in the West, particularly the United
in both living primate and paleoanthropology studies. States, has led to high caloric intakes, reduced physical
Also within the evolutionary framework, “life history activity, and high rates of obesity, cardiovascular disease,
theory” centers on the allocation of energy to somatic hypertension, and diabetes. At the same time, the
functions, such as growth and maintenance of the epidemiological transition has led to declines in infec-
body, and to reproductive functions, such as gestation, tious diseases and increases in chronic diseases of aging
lactation, and child rearing (Hill, 1993). This research and the diseases just noted that are associated with life
paradigm reintegrates areas of reproduction, demog- style. An exception to declines in infectious diseases is
raphy, and growth in new and interesting ways. AIDS and other emerging diseases, some of which are a
function of human population and social disruption
(see Chapter 27 of this volume). All of these old and
BIOMEDICAL ANTHROPOLOGY, HEALTH, newly emerging diseases offer opportunities for human
AND EPIDEMIOLOGY biologists to explore them in biological, cultural, and
environmental frameworks.
There are deep traditions of medical studies in anthro-
pology and human biology. As noted above, physical
anthropology was linked to anatomy during the nine- SOCIETIES AND JOURNALS IN HUMAN
teenth and early twentieth centuries, and many physical BIOLOGY
anthropologists were employed in medical schools
because of their expertise in gross anatomy. Some were There are several professional societies devoted to
also trained as physicians. These biomedical interests in human biology. The oldest is the Society for the Study
physical anthropology expanded to include epidemi- of Human Biology (SSHB), which was founded in
ology, public health, child growth, and nutrition, all in Britain in 1958. About a decade later, the International
the context of disease or other conditions of ill health. Association of Human Biologists (IAHB) was founded at
Johnston and Low (1984) identify biomedical anthro- a Wenner-Gren Conference in Austria. The Human
pology as being (1) based on “. . . the application of Biology Association (HBA) was established in 1974
anthropological theory to problems of health and (originally named the Human Biology Council), and
disease” (1984, p. 215) (bioculturally centered); and (2) most recently the American Association of Anthropo-
focused on a “biological outcome” (disease centered). logical Genetics (AAAG) was founded in 1993. The
Many biomedical contributions have been made with affiliation of these societies with the three main journals
anthropological knowledge in epidemiology, where in human biology is listed in Table 3.1. Human Biology is
population, the target disease, culture, and the environ- the oldest journal, dating back to 1929; the British Annals
ment intersect in complex ways. Frank Livingstone’s of Human Biology was founded in 1974; and the
(1958) research on sickle cell in West Africa was American Journal of Human Biology is the most recent
conducted from the anthropological side to the biomed- publication, having begun in 1989. Among the three
ical side, whereas Carleton Gajdusek’s (1977) Nobel journals in human biology, there are about 2500 pages
Prize winning research on Kuru in New Guinea was of articles and reviews published each year. Currently,
conducted from the biomedical side to be informed Human Biology is the official publication of AAAG
by anthropology. Correspondingly, Baruch Blumberg’s and publishes principally in population biology and
TABLE 3.1. A chronology of physical anthropology and human biology journals, societies, and major editors.
1918 American Journal of Physical Anthropology founded and edited by Aleš Hrdlička until 1942
1929 Human Biology founded and edited by Raymond Pearl until his death in 1940
1930 American Association of Physical Anthropologists established
1946 Yearbook of Physical Anthropology founded by Sherwood L. Washburn, edited by Gabriel W. Lasker
1953 Human Biology edited by Gabriel W. Lasker until 1987
1958 Society for the Study of Human Biology (SSHB) established in the United Kingdom (UK)
1963 SSHB and journal Human Biology become affiliated with James M. Tanner co-editor in the UK
1967 International Association of Human Biologists established at Wenner-Gren Conference in Austria
1972 SSHB and Human Biology become disaffiliated because of disagreements with the publisher, Wayne State University
Press
1974 Annals of Human Biology founded in the UK by the SSHB
1974 Human Biology Council (HBC) established and affiliated with Human Biology
1988 HBC and Human Biology become disaffiliated because of disagreements with the publisher, Wayne State University
Press
1988 Human Biology edited by Michael H. Crawford
1989 American Journal of Human Biology founded and affiliated with the HBC
1990 American Journal of Human Biology edited by Robert M. Malina
1994 Human Biology Council name changed to Human Biology Association
1995 American Association of Anthropological Genetics becomes affiliated with Human Biology
2002 American Journal of Human Biology edited by Peter T. Ellison
genetics; Annals of Human Biology is the official publica- a consistent practice dating back more than a hundred
tion of SSHB; and the American Journal of Human Biol- years to Franz Boas, the founder of American anthro-
ogy is the official publication of HBA. Histories of pology, and one of the principal founders of human
each of these publications and their associations can be biology. Thirdly, understanding of these biocultural
found in Tanner (1999), Crawford (2004), and Little and relations has been couched in evolutionary and adap-
James (2005). tational theory. That is, evolutionary theory contrib-
Three other societies and their journals are linked utes to or explains how humans interact with their
to human biology: the American Association of Phys- environments. Fourthly, although genetics structures
ical Anthropologists (American Journal of Physical human variation, humans are flexible in their adapta-
Anthropology, AJPA), the Society for the Study of tion to the environment; hence, there is an acute
Social Biology (Social Biology, SB), and The Galton awareness of human plasticity in response to the phys-
Society in the United Kingdom (Journal of Biosocial ical and the social environment. Finally, there has been
Science, JBS) (Johnston and Little, 2000; Alfonso and a willingness among human biologists to incorporate
Little, 2005). The AJPA publishes about 15–20% of its knowledge and expertise from other fields within the
articles in human biology, and both the SB and JBS biological, medical, and social sciences in order to
publish a majority of the papers on topics in public enrich our understanding of this most complex of
health and health-related demography. Over the years, species – Homo sapiens.
the vast majority of editors of these six journals have
been physical/biological anthropologists and human
biologists. DISCUSSION POINTS
1. Why is “race” an inappropriate concept to apply to

WHAT IS HUMAN BIOLOGY? an understanding of human variation?
2. Did Franz Boas’s championing of plasticity and his
From its earliest beginnings, human biology has made studies of human migrants demonstrate that gen-
unique contributions to scientific inquiry for a number etics played only a minor role in human variation?
of reasons. Firstly, a principal pursuit has been to 3. Was all research in human biology halted during
understand and explain the basis for human variation World War II? If not, then what kind of research
in all its dimensions, at the individual and the popula- was done?
tion levels. Secondly, because of ties with anthropol- 4. Who were the principal figures in the United
ogy, explanations have drawn on knowledge of both States who contributed to the modernization of
the biology and the culture of humans. This has been human biology? And what were their major
contributions? Who the principal figures in the Baker, P. T. (1958b). Racial differences in heat tolerance.
United Kingdom? American Journal of Physical Anthropology, 16, 287–305.
5. The 1960s were dominated by the International Baker, P. T. (1960). Climate, culture, and evolution. Human
Biological Program and its Human Adaptability Biology, 32, 3–16.
Component that included a number of human Baker, P. T. (1962). The application of ecological theory to
anthropology. American Anthropologist, 64, 15–22.
biologists from around the world. What were some
Baker, P. T. (1982). The adaptive limits of human popula-
of the basic research themes and why was this
tions. Man (New Series), 19, 1–14.
an important vehicle for the promotion of human
Baker, P. T. (1988). Human population biology: A developing
biology research? paradigm for biological anthropology. International Social
6. An important transformation in human genetics Science Journal, 116, 255–263.
studies occurred in the late 1970s. What was this Baker, P. T. (1997). The Raymond Pearl Memorial Lecture,
transformation and how did it influence our inter- 1996: The eternal triangle – genes, phenotype, and envir-
pretation of human variation? onment. American Journal of Human Biology, 9, 93–101.
7. Why is reproduction of interest to human biolo- Baker, P. T. and Daniels, F. Jr (1956). Relationship between
gists? What are some new areas of research? skinfold thickness and body cooling for 2 hours at 15 C.
8. Why is health of interest to human biologists? Journal of Applied Physiology, 8, 409–416.
What can knowledge of human biology contribute Baker, P. T. and Little, M. A. (eds) (1976). Man in the Andes: a
to our understanding of HIV? Multidisciplinary Study of High-Altitude Quechua. Strouds-
9. What are the journals that are devoted to human burg, PA: Dowden, Hutchinson and Ross.
Baker, P. T. and Weiner, J. S. (eds) (1966). The Biology of
biology research? Do they differ in the kinds of
Human Adaptability. London: Clarendon Press.
articles that they publish?
Baker, P. T., Hanna, J. M. and Baker, T. S. (eds) (1986). The
Changing Samoans: Health and Behavior in Transition.
New York: Oxford University Press.
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4 Genetics in Human Biology
Robert J. Meier and Jennifer A. Raff
By now you most likely have discerned that human of variation for the process of evolution, could not
biologists focus much of their research on variation. develop a theory of evolution that did not involve inher-
Their studies have investigated humans at multiple itance blending; his critics were quick to point this
levels of organization and interaction, from within cells problem out to him.) In reality, it was apparent that
to between large populations. The primary subject of variation was not only maintained but could be even
this chapter will be genes, and our aims are to define be enhanced over time (through selective breeding –
what genes are and what they do, how they become domesticated animals, plants). Hence, somehow par-
variable, how they are transmitted between genera- ental contributions were temporarily combined in
tions, and how they undergo evolutionary processing. children but then were subject to redistribution in sub-
More formally, the areas to be addressed are Mendelian sequent generations. And the discovery of this notion
genetics, human genetics, molecular genetics, and of heredity, called the “particulate theory” of inherit-
population genetics. In addition, there will be some ance, is largely attributed to Gregor Mendel.
discussion of newly developing research areas of inter- Gregor Mendel (1822–1884) was a clergyman, a
est to human biologists, for instance, epigenetics. Along monk, and later an abbot at a monastery in Brno
the way we will point out where certain topics covered (now in the Czech Republic), where he taught high
here are addressed, and often more fully presented, in science and mathematics, while also carrying out
other chapters of the volume. We will begin with a brief extensive research in plant hybridization (on the
look back into history when earlier notions of heredi- common pea – Pisum sativum). One of the principal
tary transmission began to be transformed into increas- experimental findings, reported in this translated and
ingly more accurate foundations that eventually led to reprinted 1865 paper (Mendel, 1962), was that certain
our current understanding of the nature of genes. paired “differentiating characters,” such as pea-pod
color, present in parents as either yellow or green, did
not “blend” in the F1 hybrid generation. Instead, there
PARTICULATE THEORY OF INHERITANCE was almost exclusively one color form. However, both
yellow and green pod colors once again appeared in the
A prevailing notion up through the nineteenth century F2 generation produced from the cross of F1 hybrids.
was that parents passed on to their offspring equal por- Hence, his “characters” seemed to be transmitted
tions of their traits, such as stature or skin color, that unchanged from parents to subsequent generations.
blended into an inseparable mixture. Thus, for example, This finding is now known as the Principle of Segrega-
a mating between a tall and short parent would result in tion, which will be defined more precisely below.
children of intermediate height, who themselves would After completing numerous hybrid and descendent
then go on to produce children of intermediate height. crosses involving a total of seven paired “differentiating
Hereditary transmission of traits according to this characters” of the pea plants, and after compiling a truly
scheme was known as the “blending theory” of inherit- remarkably close statistical conformity to expected
ance. This scheme appears to have some plausibility in probabilities, Mendel concluded that each of these
selected observations, as, in many cases, children do in “characters” was inherited without change and without
fact look intermediate to their parents. affecting the occurrence of each other. We now refer to
However, a major problem with the “blending this interpretation as the Principle of Independent
theory” was that, over time, it should cause variation Assortment, which also will be covered below.
to diminish in each generation, and ultimately to Mendel0 s research and his Principles of Inheritance
disappear. (This conundrum was a significant issue apparently were not known to Charles Darwin (1809–
for Darwin, who, while recognizing the importance 1882), who incidentally had devised an ingenious
48
Genetics in Human Biology 49
notion of inheritance known as Pangenesis, that

Parents AO ´ AO
involved units of heredity he called gemmules. Since
Darwin proposed that gemmules were subject to modi- Gametes A, O A, O
fication during an organism0 s lifetime, Pangenesis is
often likened to a prevailing theory of the day, that of A O
“inheritance of acquired characteristics,” usually
F1 offspring A½ AA AO
closely identified with the writings of an eighteenth/
nineteenth century French naturalist, Jean-Baptiste O½ AO OO
Lamarck.
4.1. Principle of Segregation.
In actuality, it was not until around the turn of the
twentieth century that Mendel0 s work was “rediscovered”
by two European researchers, Carl Correns and Hugo Considering advancements following Mendel0 s work,
de Vries, and possibly a third, Erich von Tschermak. codominance means that A and B alleles are expressed
De Vries is generally credited as the first to acknowledge equally in the phenotype. In sum, the observed blood
Mendel0 s prior groundbreaking research. Around this types are A, B, AB, and O. Of note here, both the
time, in 1903, other historically relevant events occurred, A and B blood types could be concealing the presence
including the relabeling by Johannsen of Mendel0 s “char- of an O allele that would reappear for example, if
acters” as “genes” and the formation of the Sutton– parental genotypes AO and BO were to mate and pro-
Boveri hypothesis that stated that “characters” were duce offspring having the OO genotype. In this illus-
carried on chromosomes (see Peters, 1962). tration of the Principle of Segregation, alleles making
up the parental genotypes AO and AO separate cleanly
during the formation of gametes, and this can result
MENDELIAN GENETICS in novel recombined paired alleles or genotypes, as
shown in Figure 4.1.
With this abbreviated background into the history of This mating results in a phenotypic segregation
genetics, we can now proceed to introduce the basic ratio as 3(A):1(O), and genotypic ratio of 1(AA):2
concepts and terminology associated with Mendelian (AO):1(OO). An exception to the segregation principle
genetics; that is, a description of how gene transmis- occurs when homologous chromosomes fail to separ-
sion and inheritance operates. Illustrations and ate during meiosis, a condition termed nondisjunction.
examples will apply to humans, but the discussion will Nondisjunction of chromosome 21 is a major cause of
build on the essentials of Mendel0 s and other early Down0 s syndrome, and sex chromosome aneuploidy
relevant scientific discoveries in genetics that may have (abnormal chromosome complement) has resulted in
dealt with nonhuman organisms for which an under- such conditions as XO (Turner female), XXY (Kleinfel-
standing of basic principles applies equally. ter male), XXX females, and XYY males.
Mendel0 s Principles of Inheritance can be illustrated In a simplified version of the Rh system, which,
through two widely known human blood groups, the once again is serologically important for transfusion
ABO and Rhesus (Rh) systems. (See Chapter 13 of this purposes, two alleles are present, D and d. These
volume for an in-depth coverage of these and other combine to form three genotypes, DD, Dd, and dd,
classical genetic markers.) Of clinical significance (in yet produce only two phenotypes, D-positive and
terms of adverse blood transfusion reactions due to D-negative, since the d allele is recessive to the D allele.
mismatching blood types), the ABO system is inherited Mendel0 s Principle of Independent Assortment can be
according to three gene variants, or more formally demonstrated by the fact that the inheritance of a
termed “alleles,” A, B, and O. Parents will produce person0 s ABO blood type is not conditioned by that
gametes that contain only one allele of the gene-pair person0 s Rh blood type. Gametes contain all possible
found in their genotype. Then at fertilization, any two combinations of the two alleles at the two loci. This
of these alleles combine in forming a genotypic makeup is illustrated by the Punnett square presented in
of AA, AO, BB, BO, OO, or AB. Genotypes are designated Figure 4.2. The mating pair in Figure 4.2 yielded a
as homozygous if they have the same alleles, as in AA, phenotypic segregation ratio of 9:3:3:1, or:
BB, and OO, or heterozygous if they have different
• nine persons who are blood type AD-positive
alleles, as in AO, BO, and AB.
• three persons who are blood type AD-negative
Phenotypic expression in the ABO system, which
• three persons who are blood type OD-positive
can be observed in a serological test, is controlled by
• one person who is blood type OD-negative.
inheritance rules in which the A and B alleles are
dominant over O, and are codominant to each other. The ABO and Rh blood groups are inherited inde-
In the terminology that is consistent with Mendel0 s pendent of each other because they happen to be
use, the O allele is recessive to both A and B. located on separate chromosomes and thus are not
50 Robert J. Meier and Jennifer A. Raff
thus does not contribute to genetic variation nearly as

Parents AO, Dd ´ AO, Dd
much as segregation within loci and independent
Gametes AD, Ad AD, Ad assortment of chromosomes.
Additional sources of genetic variation are in the
OD, Od OD, Od
investigative stage at this time, and not yet fully under-
stood in terms of frequency nor in evolutionary signi-
F1 offspring AD Ad OD Od ficance. Included here are transposons (“jumping
genes”) that are readily found throughout the genome
AD½ AA DD AA Dd AO DD AO Dd as repeated DNA sequences. These sometimes are
referred to as “junk” DNA, but their function, possibly
Ad½ AA Dd AA dd AO Dd AO dd
regulatory in nature, are beginning to be understood
(Ahnert et al., 2008). Finally, there is some speculation
OD½ AO DD AO Dd OO DD OO Dd
that horizontal gene transfer, which is known to have
Od½ AO Dd AO dd OO Dd OO dd played an important role in bacterial evolution, might
also be found in higher organisms.
4.2. Principle of Independent Assortment.
We leave this section on Mendelian genetics with a
note of appreciation for the work that built a founda-
linked. Of experimental importance and historical tion upon which Darwin0 s evolutionary thinking could
significance, Mendel0 s seven paired sets of “differenti- thrive, but only after some needed reconciliation
ating characters” of garden peas were each located on between geneticists and proponents of evolution.
separate chromosomes and hence were not linked, Human biology researchers were obviously beneficiar-
and all assorted independently from one another. It ies of this important historical development. This
is not known for sure if Mendel0 s choice of traits was matter will be covered under the topic of “a Modern
fortuitous or by design, or perhaps some of each. Synthesis” later in the chapter.
Interestingly, later experiments between 1905 and
1908 on inheritance patterns in sweet peas (a close
relative of garden peas) done by Bateson and Punnett HUMAN GENETICS AND MODES
did demonstrate linkage, yet they seemed uncertain of OF INHERITANCE
how to interpret their results (Bateson and Punnett,
1962). As noted above, alleles at a given locus interact with
Looking ahead to our discussion of evolutionary each other in expressing a phenotype. For all the traits
genetics, it is important to point out here that Mendel0 s studied by Mendel, this was one of dominance and
two principles of inheritance are significant ways for recessivity. Of some historical interest, it was initially
secondarily producing genetic variation that ultimately thought that the dominance referred to traits that
arises through mutation segregation of alleles and would become predominant or that their frequency
independent assortment, and also the reshuffling of would increase at the expense of recessive traits. That
maternal and paternal chromosomes, producing off- notion was dispelled by G. H. Hardy (1962) in his 1908
spring that possess multiple combinations of their par- paper that essentially established the Hardy (later
ental genotypes. Indeed, sexual reproduction offers joined with Weinberg) Principle of Equilibrium. This
continuing replenishment each generation of more development will be taken up later.
variation which evolution can operate upon from new Here, we generalize on the concept of allellic inter-
variants supplied by mutation. As if there might even action. To do so, first requires that a distinction be made
be a call for more variants, chromosomes regularly among chromosomes found in a karyotype. Karyotype
break up linked alleles and recombine them through a refers to the total complement of chromosomes present
crossing-over process. When crossing-over takes place in the cell nucleus, at one time thought in humans to
between nearby loci, previously linked alleles are number 16, later 48, and then shown for certain to be
recombined. However, the probability of a cross-over 46 (Tjio and Levan, 1956). Chromosomes occur in
event occurring depends on how closely the linked loci 23 homologous pairs, each half of which had descended
are positioned. Tightly linked loci may greatly reduce from the maternal and paternal lines. Twenty-two pairs
the likelihood of a crossing-over involving them. Con- are designated as autosomes, while the twenty-third
versely, widely separated loci may have a 50% chance pair constitutes the sex chromosomes, either XX for
of a cross-over between them, and that amounts to females or XY for males. Figure 4.3 shows a karyotype
independent assortment. This process perhaps is most for a human male, denoting chromosomes by number
important for evolution if it takes place between hom- and by groupings.
ologous chromosomes, and is equal and reciprocal. With this background on chromosomes we can
Overall, the rate of crossing-over is relatively low and now distinguish the kinds of interactions that alleles
However, if dominant they will appear more often in

females, who can be either homozygous or heterozy-
gous and express the trait. Obviously, there is no
father-to-son inheritance of X-linked traits. Normally,
1 2 3 4 5 Y-linked traits only are found in males, except for very
A B rare instances of crossing-over to the X chromosome.
Examples of X-linked recessives are hemophilia and
color-blindness (the latter does have other loci that
affect its expression). An example of X-linked domin-
6 7 8 9 10 11 12 ant trait is a human blood group, Xga. Sex-linkage on
C the Y-chromosome of course relates to loci that control
the development of maleness, such as the testis-
determining locus.
13 14 15 16 17 18
As might be anticipated, pedigree analysis and gen-
D E
etic family histories did not always yield unambiguous
results. We have already mentioned one of these in the
19 20 21 22 X Y case of codominance in the ABO and MN blood groups,
F G where two alleles can be equally expressed. In general,
4.3. Karyotype of a human male. From http://homepages.uel. one can observe a range of expression due to incom-
uk/V.K.Sieber/human.htm. plete dominance at a locus. This has been found for
the phenylthiocarbamide (PTC) taster trait, whose
strength of expression is due its interaction with
can express. This is simply stated in terms of phenotypic another locus. The PTC trait is discussed further in
traits, or modes of inheritance categorized as autoso- Chapter 13 of this volume.
mal dominants or recessives, and sex-linked dominants Another exception to a single heredity transmission
or recessives. Just as in the experiments performed by model is that of genetic heterogeneity. For example,
Mendel, human researchers examined the outcomes of retinitis pigmentosa, an eye pathology, may be
many matings across successive generations of many inherited as an autosomal dominant, autosomal reces-
pedigrees to establish these modes of inheritance. Twin sive, or be X-linked.
studies were also effectively employed to elucidate Two additional departures from common modes
inheritance patterns, which is now more precisely aided of inheritance are incomplete penetrance, i.e., whether
through methods of genetic analysis and DNA testing. the possessed genotype is expressed at all, and variable
These issues will be discussed later. expressivity, where persons with the same geno-
Most basic phenotypic expressions were observed type express a trait to varying degrees in their pheno-
during the discovery of human blood groups during type. For medically important traits, this variability
the first half of the twentieth century. We have already presents as clinical severity. Reduced penetrance and
cited the ABO blood group that was discovered in 1900 variable expressivity in the phenotype probably result
within which the A and B alleles were found to be from extenuating circumstances, implicating aging
dominant to the recessive O allele. To this can be added and environmental effects, or possibly interaction with
a host of phenotypic traits, with dubious functional other genes. Late-onset diseases, such as Huntington0 s
purpose, that are shown in human pedigrees to be disease (under autosomal-dominant control), do not
autosomally inherited, and for the most part, to be manifest themselves in 100% of affected persons, but
either dominant or recessive in their expression. This this may be due to these individuals not surviving long
list includes such traits as earlobe attachment, enough for the diseases to become clinically diagnosed.
hitchhiker0 s thumb, absence of a widow0 s peak, and In completing this section on modes of inheritance
no freckles, all of which are deemed to be recessively it is appropriate to include a brief mention of
inherited. At one time, it was thought that eye (iris) mitochondria. In humans, these organelles are exclu-
color was determined by a simple Mendelian inherit- sively inherited from the mother, although there has
ance pattern whereby brown was dominant and blue been a reported case of paternal inheritance (Schwartz
recessive, but that model has since been replaced by and Vissing, 2002). Each mitochondrion contains
one that posits several genes in control of the trait many copies of mitochondrial DNA (mtDNA), and
(Duffy et al., 2007). As would be expected for autoso- since each copy forms an intact circular structure com-
mal traits, there should be an equal frequency posed of 16 569 base pairs, they can be considered
expressed in both sexes. equivalent to a single gene or locus. Due to a high
On the other hand, X-linked traits, if they are reces- mutation rate that provides an abundance of genetic
sive occur mostly in hemizygous (haploid X) males. variation, mtDNA has been of tremendous value in
tracing ancient human matrilineal ancestry and gene-one enzyme” hypothesis (each gene is utilized by
evolution, in seeking out more recent genetic relation- the cell to produce a single enzyme). This hypothesis
ships, and in determining personal identification. was later refined to accommodate the broader range of
Some of this research can be complicated due to known gene products. Currently in molecular biology
mtDNA-related diseases (such as Leber hereditary and biochemistry, genes are often defined as DNA seg-
optic neuropathy – LHON) in which cells can have a ments which are used as templates from which comple-
mixture of normal and mutant mitochondria, a condi- mentary RNA molecules are produced (transcribed).
tion known as heteroplasmy (Jacobi et al., 2001). Functionally, protein-coding genes consist of the tran-
scribed sections of DNA (also known as open reading
frames), noncoding regulatory regions known as pro-
MOLECULAR GENETICS moters, as well as other sequences (sometimes at con-
siderable distance from coding sequence) that assist in
Molecular genetics examines the mechanisms by which enhancing or repressing transcription. Whether such
genetic material and environmental conditions act in distant regulatory elements should be included in the
concert to influence the phenotype of an organism definition of “gene” is currently a topic of debate
throughout its development and life, as well as the (Gerstein et al., 2007; Pesole, 2008).
mechanisms that allow the transmission of an In recent times, definitions of genes have empha-
organism0 s genetic material to its offspring. In this sized their sequence and architecture, as researchers
section, we briefly survey these important phenomena, struggle with the daunting task of identifying individual
with a particular focus on current findings in human genes within huge stretches of genomic DNA. Identify-
genetics. ing genes on the basis of their DNA sequence is consid-
erably less straightforward for eukaryotic genomes
than prokaryotic genomes. Within an open reading
Genes
frame (ORF), a typical eukaryotic gene will have DNA
The usual starting point for a discussion of molecular sequence that encodes amino acids (exons), often sep-
genetics is the definition of the gene itself. The concept arated by noncoding DNA sequences (introns) which
of a gene is somewhat nebulous, having been shaped by are removed (spliced) from the RNA prior to translation.
findings in molecular biology, developmental biology, The number of introns present within genes varies con-
evolutionary biology, and (most recently) large-scale siderably, but the average vertebrate gene contains 5–8,
analyses of the genome, transcriptome, and proteome. and introns seem to be surprisingly well conserved
In the classical definition, genes are conceptualized as (Koonin, 2009). By contrast, prokaryotic genomes do
operational units of inheritance with discrete physical not have introns; instead, there is a direct correspond-
locations on chromosomes (hence “locus” is often used ence between the sequence of prokaryotic DNA and the
near-synonymously with “gene”). A functional defin- RNA product of that gene (Figure 4.4).
ition of the gene was provided by Beadle and Tatum It is no exaggeration to state that insights from the
(1941); their elegant mutational analysis on Neurospora sequencing of the genomes of humans and major
strains supported the conceptualization of the “one model organisms have revolutionized our
Enhancer sequences Promoter Poly-A addition site

Exon Intron Exon Intron Exon
DNA 5′ 3′
Upstream Downstream
Transcription
Initial transcript
(pre-mRNA)
Introns excised and
exons spliced together
Coding segment
mRNA G P P P A A A ... A A A
5′ Cap Leader Trailer Poly-A tail

Start Stop
codon codon
4.4. Diagram of a eukaryotic gene, its initial transcript, and the mature mRNA transcript. From
Futuyma (1998), p. 44.
understanding of molecular genetics. For example, 5′ 3′

emerging research on the transcriptome (the totality
of transcripts within a cell) has revealed that our C G
understanding of genes as discrete loci on chromo-
A T
somes is too simplistic; transcribed regions overlap
each other, introns can be used for coding functional C G
products, and a single gene can produce several types
of protein. Therefore, although a gene can still be con- G C
ceptualized as a stretch of DNA sequence that is used to
T A
produce RNA or protein, there is still considerable
discussion regarding the limitations of this definition C G
(Beurton et al., 2000; Gerstein et al., 2007; Pesole, 2008). T A
DNA and RNA A T
The complex molecule that comprises the genetic G C

material – DNA – has been well characterized bio- T A
chemically since its structure was published by C G
Watson and Crick (1953). DNA is composed of a back-
bone of covalently bonded phosphates and 20 deoxy-
ribose (five-carbon) sugars to which nitrogenous
bases (adenine, guanine, thymine, and cytosine) are G C
attached, forming a long asymmetric polymer. The A T
terminal phosphate end of the DNA strand is desig- C G
nated as the 50 end, and the terminal hydroxyl end is
5′
designated as the 30 end. Each of the four bases is able 3′
to form noncovalent hydrogen bonds with another 4.5. The DNA double helix. From Futuyma (1998), p. 44.
base: adenine (A) forms two hydrogen bonds with
thymine (T), and guanine (G) forms three hydrogen associated proteins (most notably histones) and RNA
bonds with cytosine (C). Because of this specific molecules. Except during mitosis, this DNA-protein-
pairing, a strand of DNA is able to form a stable asso- RNA complex exists in a fairly uncondensed form
ciation with another strand having the same sequence known as chromatin. Chromatin can be chemically
of bases in reverse polarity. That is, the 50 end of one altered and further condensed with the help of histones
strand sits opposite to the 30 end of the complementary and RNA to prevent or facilitate access by transcrip-
strand. Although the hydrogen bonds between bases tional machinery in a process known as chromatin
are individually weak, in aggregate they produce a remodeling. Portions of the chromosome thus rendered
stable (though not unbreakable) double helical struc- inactive are known as heterochromatin, while genes
ture (Alberts et al., 2002) (Figure 4.5). within the less condensed euchromatin can be
The structure of RNA is quite similar to DNA, expressed (Wallrath, 1998).
except that ribose is used as the sugar instead of deoxy- The entire complement of human chromosomes
ribose, and the base uracil (U) is used in place of contains an estimated three-billion nucleotide pairs
thymine (T). RNA is often single stranded, and is less (ENCODE Project Consortium, 2007). As described
stable than DNA. As we discuss later, mRNA undergoes previously in this chapter, chromosomes are the
extensive editing in order to generate a molecule stable vehicles for transmitting genetic information from
enough to serve as a template for protein synthesis. parents to offspring. As such, in addition to being used
Although DNA constitutes the genetic material of all as the template for the synthesis of proteins and RNA
known living organisms, virus genomes are composed needed for cellular functions, each chromosome also
of RNA, and it has been hypothesized that early forms must be duplicated and apportioned correctly into the
of life on earth also utilized RNA as their genetic daughter cells during cell division.
material (for a review of the “RNA World” hypothesis, Certain structural features of eukaryotic chromo-
see Bartel and Unrau, 1999). somes play key roles in these processes. Centromeres
are heterochromatic regions found in the center (meta-
centric) or towards the end (acrocentric) of chromo-
Chromosome architecture
somes. Centromeres function during cell division as
Eukaryotic chromosomes are composed of long attachment points for microtubules through structures
stretches of double helical DNA, packaged with known as kinetochores, which position chromosomes
Leading-strand template
Newly synthesized
strand DNA polymerase
New
Okazaki RNA primer
Sliding fragment DNA helicase
clamp DNA polymerase/primase
Single-strand
Lagging-strand
DNA-binding protein
template
Clamp loader
DNA polymerase
4.6. The mammalian replication fork. From Alberts et al. (2002), p. 254.
during mitosis and meiosis. The other important struc- known as DNA polymerase, cannot initiate DNA syn-
tural feature of chromosomes is the telomere. Telo- thesis de novo; it can only add bases to an already
meres are composed of noncoding, repeating DNA existing nucleotide chain. Therefore, short regions of
sequences found at the ends of each chromosome, RNA sequence (called primers) are created by enzymes
which protect the coding sequences during DNA repli- on both template strands in order to allow the poly-
cation (Greider, 1998). merase to bind and begin synthesis.
Once the DNA polymerase has bound to the origin
(assisted by additional proteins), DNA synthesis begins
Replication
along both strands of the replication fork, terminating
At the end of their description of the structure of DNA, when double-stranded DNA is encountered at the next
Watson and Crick noted in perhaps the most famous replication origin. DNA polymerase can only add deox-
understatement in biology: “It has not escaped our yribonucleotides to the 30 end of a growing DNA
notice that the specific pairing we have postulated strand. Therefore, synthesis proceeds continuously
immediately suggests a possible copying mechanism opposite to the 30 –50 template strand (called the leading
for the genetic material” (1953, p. 737). The generation strand) but can only synthesize short fragments oppo-
of new cells and the transmission of genetic informa- site the 50 –30 (lagging) strand, as their synthesis moves
tion from parent to offspring requires the precise the polymerases away from the replication fork.
duplication of an organism0 s genome. Understanding Numerous short DNA segments, known as Okazaki
the chemical properties of the DNA strands was the key fragments, are thus produced repeatedly by the poly-
to understanding the mechanisms of this process. merases, with the intervening gaps filled by an add-
Because the nucleotide bases pair only with their itional enzyme (Meyers, 2007).
proper complementary base (A with T, G with C), DNA Given the polymerase0 s directional constraints, the
replication is semiconservative. That is, each strand of replication of the ends of lagging strand eukaryotic
the original chromosome is used as a template to gen- chromosomes is problematic. After the RNA primers
erate a complementary daughter strand. In human are removed from the newly synthesized complement,
chromosomes, replication begins simultaneously at and the Okazaki fragments are ligated together, there
several points per chromosome known as origins of still remains an unsynthesized segment at the very end
replication, located between 5 and 300 kilobases apart of the DNA strand. Although telomers protect the ends
from each other. Numerous proteins are required to of coding region sequence from degradation, over suc-
initiate DNA synthesis. Topoisomerases, helicases, and cessive rounds of replication, chromosomes become
other associated enzymes work to unwind the two progressively shorter without the action of an enzyme
strands of DNA ahead of the replication machinery, called telomerase, which adds DNA repeats to the end
stabilize the separated strands and relieve upstream of the 30 end. Telomere shortening appears to be asso-
torsional stress caused by the unwinding of DNA. The ciated with cell senescence (aging) (for a review, see
enzyme that synthesizes the daughter strand of DNA, Greider, 1998).
MITOSIS Prophase Metaphase Two daughter cells
2n 2n
Centromeres divide and sister

Individual chromosomes chromatids separate during
Parent cell align at the ecuatorial anaphase, becoming daughter
(2n) (metaphase) plate. chromosomes.
4.7. Mitosis. From Futuyma (1998), p. 32.
An extremely important property of DNA polymer- chromatids) by microtubules, which serve to position
ase is its 30 –50 exonuclease ability, which serves as a chromosomes correctly during mitotic events. During
“proofreader” for the genome. As DNA bases are added metaphase, the chromosomes line up at the approxi-
to the daughter strands, an occasional erroneous base mate center of the cell – an extremely important step
is incorporated. DNA polymerase detects such mis- for ensuring the correct distribution of each chromo-
matches and excises the inappropriate base such that some into the daughter cells. During anaphase the
the error rate for DNA replication is estimated to be cohesion between the sister chromatids is dissolved
only one in a billion bases. Although proofreading and they are pulled apart towards the poles. The
likely slows the progress of the polymerase, its proces- nuclear envelope is reformed around the chromosomes
sivity is enhanced by the presence of clamp proteins, during telophase, and following cell division they de-
which help to maintain contact between the polymer- condense into transcriptionally active chromatin. Thus,
ase and the DNA template (Figure 4.6). at the end of mitosis each daughter cell has received one
copy (in the form of one of the sister chromatids) of
each chromosome (for a detailed description of mitosis,
The somatic cell cycle and mitosis
see Alberts et al., 2002) (Figure 4.7).
The majority of cells in the human body (somatic cells)
do not contribute genetic information to the next gener-
Meiosis
ation. Instead, they perform a variety of roles in growth
and development which constantly require the gener- Meiosis is a process by which a diploid germline cell is
ation of new cells. The process by which a diploid divided twice to produce four haploid daughter cells
somatic cell divides to produce two identical diploid called gametes. Gametes from each parent are com-
daughter cells is known as mitosis. The cell cycle consists bined during fertilization to produce a diploid zygote,
of four discrete phases: G1 (during which the cell with both halves of its genome contributed equally by
assesses, via checkpoints, that it is ready for proliferation the two parents. The initial stages of meiosis are simi-
and DNA replication); S (during which chromosomes are lar to mitosis. DNA replication produces a copy of each
duplicated as described above); G2 (during which the cell chromosome, and microtubules are produced at the
pauses to verify via additional checkpoints that the spindle poles. However, unlike mitosis, the microtu-
chromosomes are ready for mitosis); and M (during bules attach to only one kinetochore on each pair of
which chromatin condenses and mitosis occurs). joined sister chromatids. During prophase I, homolo-
Mitosis itself consists of several steps. During pro- gous chromosomes (one inherited from each parent)
phase, chromosomes condense within the nucleus; it is pair with each other and recombination takes place
here that the classical “X” shape of sister chromatids between them. As described previously in this chapter,
(joined at the centromere) can be first observed. The recombination is a major generator of genetic diver-
cell undergoes a number of changes to prepare for sity. During metaphase I, the chromosomes form two
mitosis. Cellular structures which organize microtu- rows in the center of the cell, with each chromosome
bules – centrosomes and centrioles – duplicate and positioned across from its homolog. This alignment is
migrate to opposite poles in the cell. From these pos- critical to ensure the proper ploidy of the gametes.
itions, they generate long microtubule polymers which During anaphase I, the homologous chromosomes are
make contact with kinetochores on the centromeres of pulled apart, one to each pole; both sister chromatids
both sister chromatids. The nuclear envelope breaks from each chromosome remain attached to each other.
down during prometaphase, and the chromosomes Cell division takes place during telophase I, producing
are “captured” (at the kinetochores of both sister two daughter cells, each with only one copy of each
duplicated chromosome. During the next phases of (rRNA) serve essential roles in translation of mRNA
meiosis (prophase II–metaphase II), the chromosomes into polypeptides. Small nuclear RNA (snRNAs) are
(still consisting of two sister chromatids) are attached involved in splicing, small nucleolar RNAs (snoRNA)
to microtubules via kinetochores on both sister chro- function in processing the rRNA transcript (Eddy,
matids. In a process similar to mitosis, the chromo- 1999), and long introninc noncoding RNAs appear to
somes form a single line along the center of the cell. have an important role in gene regulation (reviewed in
During anaphase II, sister chromatid cohesion is lost, Louro et al., 2009).
and the sister chromatids are pulled apart, one to each
pole of the cell, which subsequently divides during Regulation of gene expression
telophase II. As a result of this process, haploid The timing and location of gene expression is critical
gametes bearing half of the number of chromosomes for normal development and function of an organism,
seen in diploid cells are produced. and the regulation of gene activity is an extremely
Problems with the carefully orchestrated align- complex process. Although a subset of genes (known
ments of the chromosomes can lead to nondisjunction – as housekeeping genes) is constitutively active, environ-
a condition in which the daughter cells receive an mental conditions can require precise changes in the
improper number of chromosomes. This is responsible expression of many genes. Although gene expression
for trisomy diseases as have been discussed above. occurs during post-transcriptional processing of
mRNAs, during translation, and during post-transla-
tional modification of polypeptides, its regulation
From DNA to phenotype
mainly occurs at the transcriptional level.
Information contained within the genome is utilized by A major mechanism of transcriptional control
the cell to make proteins and RNA critical for the involves the structural or chemical alteration of DNA
development and function of all organisms. This pro- itself. For example, acetylation of histones can cause
cess has been characterized as the “Central Dogma” of them to “loosen” DNA, making it more accessible for
biology by Francis Crick: DNA is transcribed into RNA, transcriptional machinery. DNA methylation is a
and RNA is translated (ultimately) into protein in a common mechanism for gene silencing. In mammals,
unidirectional process. Subsequent research, however, this usually consists of methylation (addition of CH3
continues to provide numerous exceptions to this groups) of cytosine bases when they are immediately 50
model. Here, we will briefly review the processes of to guanine bases (designated as “CpG” motifs, which
DNA transcription, post-transcription processing, and are commonly found in promoters).
translation of RNA into protein in eukaryotes, with a One well-studied example of long-term gene regula-
special emphasis on lessons learned thus far from the tion is dosage compensation in mammals. Because sex
human genome and transcriptome. determination in mammals is achieved by the presence
of a Y-chromosome, male mammals are haploid for the
Transcription genes on the X chromosome. Dosage compensation is a
Transcription is the means by which DNA is used as a phenomenon in which all of the genes on one randomly
template for the production of a complimentary RNA chosen X chromosome in each cell in a female mammal
molecule. These gene products have diverse roles are suppressed so that the levels of gene product will be
within the cell. A subset of RNA transcripts are trans- comparable between the sexes. This appears to be
lated into chains of amino acids by cellular machinery achieved by two mechanisms; chromatin remodeling
to be used as components of proteins. RNA used to (induced by the coating of the X chromosome with
convey the genetic instructions to the translation machin- RNA) initially silences X chromosomal genes during
ery for protein production is known as “messenger” RNA development, followed by DNA methylation to achieve
(mRNA). As will be discussed below, the process of creat- permanent suppression (Cedar and Bergman, 2009).
ing and using mRNA for protein synthesis in eukaryotic Transcription is also controlled at the level of indi-
cells is highly complex. vidual genes by cis regulatory elements (sequences of
Less than 2% of the human genome contains DNA DNA on the same strand as the transcribed gene).
that codes for protein. Yet, it has recently been Located within and just upstream of the promoter,
reported that the vast majority of the human genome these sites bind a family of proteins, called transcrip-
analyzed thus far is transcriptionally active (Birney tion factors that are required for transcription initi-
et al., 2004; ENCODE Project Consortium, 2007). Far ation; by increasing or decreasing the levels of
from being “junk DNA” as previously labeled, noncod- transcription factors the cell is able to control the rate
ing DNA appears to play an important role in diverse of transcription of particular genes. Additional control
cellular processes. It is known that this (noncoding) over gene expression is brought about by proteins that
RNA is used in many different cellular functions. For bind to genetic elements more distant from the gene,
example, transfer RNA (tRNA) and ribosomal RNA and are able to enhance or repress transcription.
Mechanisms of transcription frame is specified by an initiation codon (AUG). The

Transcription begins with the binding of a transcrip- template is “read” by protein/RNA complexes known as
tion factor to the promoter region of a gene. In many ribosomes. Ribosomes recruit tRNAs, which are adap-
eukaryotic genes, the region of the promoter that tor molecules whose structure contains a three letter
binds the transcription factor is located 20–30 bases “anti-codon” complementary to an mRNA codon, and
upstream of the transcription start site, and is named can bind the appropriate amino acid that codon speci-
the “TATA” box (after a commonly found motif fies. Once the mRNA/ribosome/initiator tRNA complex
TATAAAA). The transcription factor subsequently has assembled at the first codon (assisted by numerous
recruits to the promoter numerous functionally associated proteins), the ribosome moves along the
related proteins that collectively are known as the mRNA in three base increments, recruiting the appro-
preinitiation complex. Among these proteins is one of priate tRNA for each codon. The tRNA transfers its
several DNA-dependent RNA polymerase enzymes, attached amino acid to the growing polypeptide chain,
each of which produces a specific type of RNA. Pol then disassociates from the complex. When the trans-
I produces the large rRNA subunit, pol III produces lation machinery reaches the “stop” codon in the
the small rRNA subunit, tRNA, and the small nuclear mRNA, translation is completed and the complex
RNAs, and pol II is used to make mRNA. Unlike DNA dissociates.
polymerase, RNA polymerase is able to bind to and
use a single-stranded template. Proteins within the Proteins
preinitiation complex unwind the DNA helix in the Proteins are three-dimensional macromolecules, com-
region to be transcribed; only one strand (sometimes posed of one or more linear amino acid polymers (poly-
referred to as the Watson strand) is used as the tem- peptides). Twenty amino acids are utilized by cells to
plate for RNA production. Assisted by proteins known create proteins. These amino acids differ considerably
as elongation factors, the RNA polymerase generates in chemical properties such as size, shape, charge, and
an RNA polymer complementary to the template affinity for water, and allow for considerable diversity
sequence – with the exception that uracil is utilized in the form (and therefore function) of proteins.
instead of thymine – and terminates transcription at a Proteins have myriad roles in the cell, ranging from
specific sequence (Meyers, 2007). structural (such as forming the collagen in skin) to
participation in the complex signaling pathways of
Post-transcriptional processing in eukaryotes nearly all biological processes. Thus, the mechanisms
Noncoding RNAs undergo various structural modifica- behind genetic phenomena such as dominance and
tions, depending on their cellular role. For mRNA, the recessivity can often be understood biochemically.
transcript (pre-mRNA) is not immediately translated A loss of function (LOF) mutation, for example, fre-
into a polypeptide sequence, but instead undergoes quently generates a premature stop codon within an
significant post-transcriptional processing. Specific exon of the affected gene. The translation of the mRNA
sequences must be added to the beginning (cap) and product results in a truncated, malfunctioning protein
the end (tail) of the pre-mRNA, which specify its fate whose inactivity causes the LOF phenotype.
and protect it from premature degradation. One illustration of this phenomenon can be seen
Additionally, introns must be spliced from the tran- in spinal muscular atrophy (SMA), a neuromuscular
script. The completion of the sequencing of the human disease caused by the progressive degeneration of
genome revealed an estimated 20–25 000 protein motor neurons. It has several phenotypes, ranging
coding genes – a considerably lower number than had from mild (muscle weakness) to severe (lethality in
previously been predicted based on the number of pro- infancy). Genetically, SMA is associated with an auto-
teins known (International Human Genome Sequen- somal recessive LOF mutation caused by deletion of
cing Consortium, 2001). Alternative splicing is one exons 7–8 of the survival motor neuron I (SMN1)
mechanism which helps account for the vast diversity gene; individuals with one functional copy of this gene
of proteins that are produced by a relatively few do not develop SMA. Individuals also maintain vari-
number of human genes. Variation in transcript able numbers of a second version of the SMN gene
splicing frequently results in multiple alternative RNA (SMN2); copy numbers of SMN2 are inversely propor-
molecules produced from the same gene. tional to disease severity. SMN2 has a near-identical
gene sequence to SMN1. However, a single mutation
Translation in SMN2 results in a truncated protein product (due to
After being exported out of the nucleus into the cyto- improper splicing) in all but 10% of mRNA tran-
plasm, mRNA is used as a template to generate a chain scripts. Multiple copies of SMN2, therefore, result in
of amino acids, which are specified by three nucleotide higher levels of functional SMN protein, accounting
“words” known as codons. For a given sequence, there for the variability of the disease phenotype (Lunke
are three possible reading frames; the correct reading and El-Osta, 2009).
SOME TOOLS OF MOLECULAR GENETICS incorporated to the growing synthetic strand instead of
dNTPs, the reaction is terminated. This termination
DNA isolation
step generates a pool of different-sized fragments com-
The first step in the extraction of DNA is the breakdown plementary to the parent sequence, each terminating at
of cellular membranes and other protein components of a progressively later nucleotide position. Older sequen-
the cell. After mechanical homogenization of the sample cing methods incorporated radioactively labeled dATP
tissue (if applicable), protein is digested with a protease, into the synthetic strands, which were separated by
usually proteinase K. Sodium dodecyl sulfate (SDS) and size on a polyacrylamide gel and visualized on an
ethylenediaminetetraacetate (EDTA) are added to this X-ray film. More recently, fluorescently labeled ddNTPs
reaction to denature DNAses. DNA is then isolated from are utilized for this purpose, and automated capillary
the digested protein and other cellular constituents by sequencers have replaced the slab polyacrylamide gels
one of several methods, including phenol-chloroform as the means of visualizing the sequences. This has
extraction (which isolates the DNA in the aqueous increased the speed and ease of sequencing by many
phase), column chromatography, or binding to silica. orders of magnitude (Green et al., 1999; Meyers, 2007).
DNA can be further concentrated and purified by etha-
nol precipitation (Sambrook et al., 1989).
Sequencing: shotgun
The first drafts of the human genome sequence were
Polymerase chain reaction
published in 2001 (and completed in 2003), thus
The development of the polymerase chain reaction ushering in the genomic (or alternatively called the
(PCR) technique by Kary Mullis in 1984 was a break- postgenomic) era of molecular genetics (International
through for molecular genetics. Polymerase chain Human Geome Sequencing Consortium 2001; Venter
reaction enables the generation of millions of copies et al., 2001). Genome sequencing makes use of the
of any DNA sequence by essentially adopting the cell0 s shotgun sequencing method, which circumvents the
own mechanisms for DNA replication. Utilizing a size limitation on sequencing. Briefly, long DNA mol-
machine known as a thermocycler, double-stranded ecules are broken into random fragments for library
DNA is “denatured” into single-stranded molecules at generation. These DNA fragments are cloned into
high temperatures (95 C) by breaking the hydrogen vectors, most often either the bacteriophage M13 or
bonds between nucleotide pairs on the complementary plasmids. Clones are sequenced in enough quantity to
strands. Because the DNA polymerase enzyme only provide approximately six to eight-fold coverage of the
binds to double-stranded DNA, short DNA primers genome. The sequences are assembled into contigs
specific for the target region are annealed to the both (overlapping fragments used to infer contiguous
template strands at a slightly lower temperature (50– sequences), and assessed for quality; gaps or poor qual-
60 C). The temperature of primer annealing depends ity regions are then manually resequenced. Now that
upon the length of the primer sequence and its nucle- the molecular nature of the gene and the essentials of
otide composition. The temperature is increased for DNA sequencing have been discussed, we can turn our
the extension reaction (72 C), during which the DNA attention to the combined expression of multiple genes
polymerase adds dNTPs to the growing synthetic as they play a role in the adaptive process.
strand. This process is repeated for multiple cycles
(30–45), generating exponentially increasing numbers
of copies with each cycle (Mullis and Faloona, 1987; POLYGENIC INHERITANCE AND
Innis et al., 1990; Erlich et al., 1991; Meyers, 2007). ADAPTATION STUDIES
Several chapters in this volume deal with phenotypic

Sequencing: Sanger method
traits whose inheritance patterns are more complex
Determining the sequence of a particular stretch of than those we have been discussing under Mendelian
DNA begins with a pool of copies of the template of and molecular genetics. The formal distinction is that
interest. In a process similar to the first steps of PCR, of monogenic versus polygenic inheritance, although it
the double-stranded template is melted at high tem- is unlikely that, even for monogenic or single-gene
peratures, and the temperature is then lowered for traits, there are absolutely no other genes involved in
primer annealing. An extension reaction using DNA their expression. For polygenic inheritance, it is taken
polymerase is performed in the presence of a mixture for granted that two or more loci participate in gene–
of deoxynucleoside triphosphates containing equal gene interactions and also in gene–environment inter-
quantities of all four bases (abbreviated dNTPs), as actions, which will be discussed later. Expression of
well as dideoxynucleoside triphosphates (ddNTPs) these traits in animals and plants is what the early
which lack a 30 hydroxyl. When ddNTPs are randomly evolutionists, including Darwin, observed and studied
across biogeographic localities and through geologic heaviest to lightest. Melanin concentration as related
time periods. In animal species, researchers noted vari- to skin color is taken up in depth in Chapter 12 of this
ation in tooth and body size, body colorization, and volume. This model of iris color inheritance further
novel development of anatomical structures, and assumes that all of the loci contribute equally to mel-
acknowledged the adaptive significance of such fea- anin production, and that there are no other pigments
tures as eyes and wings. involved and no environmental effects on iris color.
This section will cover the basic genetics under- Another feature of this model is that different geno-
lying polygenic inheritance, variously referred to as types can specify the same phenotype, a phenomenon
quantitative or multifactorial inheritance. For illustra- sometimes referred to as polytypy. It further explains
tion, we will employ human eye color, or more pre- how blue-eyed parents can produce brown-eyed chil-
cisely, iris color variation among individuals. With dren as melanin concentration alleles at different loci
but a minimal observation study, iris color can be are inherited in a set that represents one of the possible
shown to differ much more than presumed under an combinations.
earlier monogenic model whereby two phenotypes We will deal with the role of the environment in the
were expressed, dominant brown over recessive blue. next section, and this effect could mean that a single
A single Mendelian locus segregating two alleles would genotype can result in different phenotypic expression
yield three genotypes, meaning there was the potential of particular traits or in affecting several aspects of the
for this model to only account for three phenotypes of phenotype (called pleiotropy). An example of plei-
dark brown, light brown, and blue, if incomplete dom- otropy is found in sickle cell anemia with multiple
inance was invoked. However, these predictions did cytological, physiological, neurological, and other
not match up with observed variation. Early geneticists effects. It is also important to point out that for some
who pondered the matter of inheritance of complex traits or conditions hereditary transmission and
traits, such as stature, that showed nearly continuous observed variation remains unclear but are suspected
variation among individuals in a large sample, from to result from genes having a major effect along with
taller to shorter, correctly reasoned that there must additive influences of other interacting genes. These
be more than one set of genes involved. Consequently, rather complex situations are being investigated
they extended Mendelian genetics to the level of poly- through quantitative trait loci (QTL) analysis, which
genic inheritance. Following their lead, if we assume attempts to map a trait to multiple chromosomes. Posi-
that iris color is controlled by two independent and tive QTL results for adult height in humans fit a model
interacting loci, each segregating two alleles, then the of a major recessive gene combined with other signifi-
number of genotypes expands to five, which, in turn, cantly contributing loci on chromosomes 6, 9, and 12
corresponds better to categories observed for iris color (Xu et al., 2002).
variation. If yet one more locus is added, then the We can conclude this section by pointing out that
model would contain three loci, two alleles each, for a many of the adaptive traits covered in Part II of this
total of seven genotypes. volume are polygenic expressions whose more precise
In general, for two allelic models, the number of mode of inheritance forms the basis of ongoing human
genotypes can be calculated as 2n þ 1, where n speci- biological research.
fies the number of loci. As the number of loci becomes
large, the distribution of genotype classes begins to
approach a normal- or bell-shaped curve. Continuously HEREDITY, ENVIRONMENT, AND
varying traits in humans, such as stature, approximate HERITABILITY
normal distributions in large samples, in part due to
their being under polygenic control, and another In this section, we will concentrate on an earlier meth-
major part accounted for by environmental effect. odology that has some historical significance in human
The basic concept of a normal distribution in polygenic biology. Indeed, it had attempted to shed light on the
inheritance can be traced back to the early part of the vexing question of nature versus nurture, of what is
twentieth century in such renowned figures as Sir more important, genes or environment. However, as
Francis Galton and Sir Ronald A. Fisher (Strachan we will see, this turns out to be a scientifically invalid
and Read, 2004). question to pose, since it cannot be directly tested. As
The model described above would permit the clas- described above, polygenic traits are under the control
sification of iris colors through a broad range of of multiple genes that are subject to environmental
expression from the darkest of brown, down through effects. What was needed in this and related cases
hazel and on to the lightest of blue. This model was a way to sort out the respective contributions
attempts to represent a genetic basis of iris color that of heredity and environment, that is, to provide an
is under the control of multiple genes that determine estimate of heritability. To some degree this could
the concentration of the brown pigment melanin, from be done by using a basic developmental difference
found in human twin types, namely, whether they were TABLE 4.1. Heritability (h2) estimates for height
monozygotic (single-egg or identical) or dizygotic and weight.*
(two-egg or fraternal). The basic methodology of twin
Variable Male Female
study is described in the following section.
Monozygotic (MZ) twin pairs were presumed to Height 0.79 0.92
differ only with respect to changes brought about by Weight 0.05 0.42
environmental factors, since they were deemed to be
Note: *Heritability estimates are based on variance data
genetically identical. A little later, we will have an found in Osborne and DeGeorge (1959).
opportunity to modify that claim. In contrast, differ-
ences between dizygotic (DZ) twin pairs would be due
to both heredity and environmental differences. There- conform to an expected higher amount of plasticity in
fore, if the differences found in MZ pairs were sub- body weight as compared with stature, as adult body
tracted from those found in DZ pairs, what remain weight is highly modifiable through diet and exercise.
should be differences only due to heredity. Based on The authors of this study were well aware that this kind
this simple calculation, a population derived statistic of comparison was made possible by the twin study,
called heritability could be estimated. Heritability (h2) but they were rather pointed in recognizing limitations
is defined as the percentage of the total variance of the method when remarking:
(having both genetic and environmental components)
that is due solely to genetic differences, in this case, Preoccupation with the problem of establishing the relative
among twin pairs. This statement is expressed in the importance of heredity or environment rather than with that
of understanding their interactions has resulted in failure to
following formula:
explore adequately the possibilities for extending the use of
h2 ¼ DZvariance MZvariance =DZvariance: twin analysis (Osborne and DeGeorge, 1959, p. 24)
Several other formulas for estimating heritability have Their plea for concentrating on gene–environment
been derived, but we will employ this one here for interactions resonates very well with current thinking.
illustrative purposes. In this application, h2 is con- Indeed, over the decades following this study, heritabil-
sidered to be a “narrow sense” version that recognizes ities from twin studies came under strong criticism on
that total phenotypic variance is equal to only the addi- a number of grounds, particularly in the area of behav-
tive genetic variance (and not the variance from all ioral genetics, and especially with respect to traits such
genetic effects) plus environmental variance. It must as personality and IQ.
be emphasized that heritability does not in any way Twins are not representative of the whole popula-
inform us about how polygenic traits are inherited or tion, and it does not appear appropriate to consider
the relative importance of either heredity or environ- the social environment within which they developed
ment in the individual phenotypic expression of these as comparable to that of singletons. One consequence
traits. Obviously, both heredity and environment are of this fact is that MZ environmental variance could
necessary. However, heritability estimates, which can be an underestimate and thereby inflate the value of
range from 0–1, have proven especially useful for plant h2. In general, heritability estimates are just that, they
and animal breeders who were looking for ways to are specific to the sample from which they were cal-
improve yields, either by experimentally altering the culated and therefore cannot be uncritically general-
parental stock and/or by changing the environmental ized to other populations. And they are never
conditions that could affect growth and development applicable toward explaining phenotypic expression
outcomes. at the level of individuals, as is often done in the
An early and nonexperimental application for popular media. Heritability estimates have been
investigating human variation through the twin study shown to differ widely when made on what were pre-
outlined above was conducted by Osborne and sumed to be comparable samples and they are subject
DeGeorge (1959). They took a series of anthropometric to change over the course of childhood development
measurements by twin type (MZ vs. DZ), and assessed (and individual life history, as with intelligence quo-
the resulted data for pattern of inheritance. Their tient estimates). These are all good reasons for
analysis did not directly calculate heritabilities, but heeding the advice of Osborne and DeGeorge and
did provide variance data from which heritability esti- paying more attention to the interaction of genes
mates could be made. These estimates are presented in and their environment.
Table 4.1 for adult height and weight.
A reasonable interpretation of these results would
Gene by environment interaction
be that height variation is more strongly attributed to
genetic differences while weight variation is more sub- To counter many of the objections and limitations
ject to environmental factors. This conclusion does found in the simple method of estimating heritability
illustrated above, newer approaches have been devised The phenomenon of non-Mendelian inheritance has
most of which take into account what is now under- been known for some time when applied to viruses
stood to be an inevitable gene and environment inter- and bacteria, but more recently it has been observed
action. The untestable question of what is more in higher life forms, including mammals and then also
important, genes or environment, has given away to an in humans. The discussion here will focus on humans,
investigation into the environmental factors that interact particularly in relation to the rapidly growing research
with the expression of genotypes. A straightforward effort in epigenetics. There is a long history of the use
example here can assist in defining this direction of the term “epigenetics” but currently it pertains to
of research. variable heritable traits that are not based on changes
For certain persons, consumption of foods contain- in DNA sequence.
ing the amino acid phenylalanine during early child- A clear-cut case of non-Mendelian inheritance, rep-
hood can result in detrimental brain development and resenting one of the many kinds of epigenetic effects,
a disorder called phenylketonuria (PKU). This was discovered in persons who carried a particular
inherited condition is due to a mutation in an enzyme mutation, a partial deletion of the long arm of chromo-
responsible for converting phenylalanine to tyrosine. some 15. It turned out that this chromosomal variant
It is an autosomal recessive disorder, and, because manifested itself differently depending upon whether it
this means that a homozygous genotype is present, was inherited through the mother or the father. If
the condition should be expressed. Yet, its expression transmitted from the mother, children were affected
is dependent upon the nutritional environment of the with Angelman0 s syndrome, and if transmitted through
child. If the child0 s diet is entirely free of phenylalan- the father, they inherited Prader–Willi syndrome.
ine, then PKU is not manifested. In this instance, a These differences occur because of a process known
given genotype may predispose a person to getting or as imprinting. More specifically, maternal and paternal
make him or her susceptible to or resistant to a par- chromosomes were differentially imprinted such that
ticular unhealthy phenotype, but that outcome will not they produced clinically distinct abnormalities during
occur unless the appropriate environmental conditions embryonic development.
are present. While, in the above example, the actual mechanism(s)
Many examples of gene by environment inter- of imprinting is not entirely understood, research has
action are now known, some having medical rele- shown that imprinting can occur through methylation
vance as PKU, and they have been incorporated in at specific junctions along a DNA sequence which
newborn screening programs in order to lessen or can be maintained over successive generations.
prevent harmful phenotypic expressions early in life. Methylation is the attachment of a CH3 group prefer-
Thus, the old saying “biology is destiny” takes on new entially at cytosine nucleotide positions, which effect-
meaning in these cases. Other examples of gene by ively silences or turns off this portion of DNA. Its
environment interactions can lead to enhanced out- principle effect is one of epigenetic regulation of gene
comes at a behavioral level, as in the case of a child expression during both embryonic and postnatal devel-
born with musical talents who is then raised by opment. Especially interesting have been the results of
parents who themselves are musicians, thereby studies showing how MZ twins become somewhat
receiving more than ample opportunities for those phenotypically differentiated due to imprinting (Fraga
talents to flourish. et al., 2005; Kaminsky et al., 2009). This finding, of
Continuing discoveries in gene by environment course, implicates subsequent transmission of environ-
research are enlightening in and of themselves but on mental influences (mediated through DNA) acquired
the horizon are still more revealing lines of inquiry that during an individual0 s lifetime, but imprinting prob-
undoubtedly will expand our understanding of the ably should not be construed as a form of Lamarkian
mutually interacting roles of heredity and environ- inheritance.
ment. These roles are considered next. Imprinting will very likely take on increasing
significance in human biology studies. (The reader
can tap into this active research area through a
NON-MENDELIAN INHERITANCE website – geneimprint.com). Likewise, epigenetics
AND EPIGENETICS has entered into discussions of evolutionary theory
(Jablonka and Lamb, 2005), indicating an ongoing
Non-Mendelian inheritance simply refers to heritable rethinking of the Modern Synthesis, to be discussed
tendencies that are not in accordance with Mendelian next. Lastly, we would remind the reader that
principles of segregation and independent assortment. Chapter 2 of this volume had a section devoted to
Not always so simple or clearly understood, they developmental adaptation and epigenetics, and some
amount to changes in phenotypes sustained over gen- of the points discussed there have been further elab-
erations without alteration of genotypic combinations. orated here.
A MODERN SYNTHESIS AND EVOLUTIONARY population genetics, which essentially defined micro-
GENETICS evolutionary studies. This section will describe the fun-
damentals of human population genetics and also
Mendelian genetics as espoused by early twentieth- provide examples from human biology that apply to
century laboratory researchers seemed to be at odds with microevolution.
post-Darwin0 s practitioners of natural selection theory, In an abbreviated form, population genetics is the
whereas today we fully embrace and necessarily incorp- study of the behavior of genes in populations. This
orate genetic principles as vital to a more complete means that there is an emphasis upon gene frequency
understanding of evolutionary processes. There have analysis, noting whether or not there are changes in
been several plausible explanations as to why genetics frequency over generations, and, if so, identifying the
and evolution were not initially synthesized into a new underlying causes for those changes. Conversely, there
paradigm, not the least of which is the fact that the two are also reasons why gene frequencies are maintained
camps, laboratory experimentalists versus field natural- or remain stable over successive generations. To illus-
ists, were engaged in separate research pursuits that in trate these points, let us begin with a simple gene, or
turn did not offer abundant opportunities for fruitful actually, allele frequency calculation.
interactions of ideas. However, a meeting of the minds The example of the MN blood group system will be
did take place around the 1920s when at first there used. This system has two codominant alleles, M and
was the recognition of neo-Darwinism, which added N, which yield three distinct genotypes, MM, MN, and
mutation and genetic variation into its formulation of NN. If we were to have studied a sample of 100 persons
natural selection theory, later followed by what came to and found their genotypic proportions to be 25 of MM,
be labeled the “Modern Synthesis.” Fundamentally, the 50 of MN, and 25 of NN, then we can directly count the
Modern Synthesis proposes that evolution occurs as a number of M and N alleles in this sample.
result of selection acting upon genetic variation gener-
Let p ¼ frequency of M and q ¼ frequency of N
ated within natural populations through mutation and
recombination, as well as from gene flow between Then p ¼ all of MMð25Þ þ 1=2 of MNð25Þ ¼ 50=100 ¼ 0:5
groups, and is subject to random drift, particularly And q ¼ all of NNð25Þ þ 1=2 of MNð25Þ ¼ 50=100 ¼ 0:5
in small, widely scattered populations. Over extended
Note that: p þ q ¼ 1:0:
periods of time, multiple generations and the possible
subdivision of original populations, evolution leads to Through this example, we have broached the most
genetic divergence and speciation. This section briefly important concept in population genetics, the Hardy–
describes the tenets that will be discussed next under Weinberg Theorem. Hardy, a British mathematician,
the topic of population genetics. and Weinberg, a German physician, independently dis-
With the application of more recent terminology, the covered that, under certain specifiable conditions,
Modern Synthesis might well be viewed as conjoining genotypic proportions within a population will remain
what are now described as microevolution and macro- in equilibrium and will not change over successive
evolution, the comfortable coupling of which continues generations. Genotypic proportions will in fact corres-
to be questioned by some theoreticians. In fact, it is pond to an expansion of a binomial expression con-
important to note that the Modern Synthesis is continu- taining p and q allele frequencies. In algebraic form,
ally under revision as important questions (and the accu- this would read:
mulation of new data) about the mode and tempo of
ðp þ qÞ2 ¼ p2 þ 2pq þ q2 :
evolution are investigated and debated. For example,
what determines the rate of evolutionary change? Does For the Hardy–Weinberg Equilibrium to be present,
evolution proceed gradually or in relatively rapid burst, the following conditions are expected to apply:
as hypothesized in the model of punctuated equilibrium?
1. the population is infinitely large in numbers of
At what level does selection operate, on the gene, the
individuals;
individual or kin group, or all of the above? (Refer back
2. there is random mating; and
to Chapter 1 of this volume for an extended discussion of
3. there is no evolution.
this matter.) Future developments in genetics and biol-
ogy can be expected to enliven these debates and also We will discuss each of these variables in turn, bring-
enlighten our understanding of evolution. ing out some major features that will help to illustrate
the power and profundity that comes from testing
populations with such a simple mathematic formula-
HUMAN POPULATION GENETICS AND THE tion, the Hardy–Weinberg Equilibrium test, hereafter
HARDY–WEINBERG EQUILIBRIUM designated H-W. Applying the H-W test to the MN
blood group discussed above yields equilibrium
The Modern Synthesis united genetics with evolutionary expected genotype frequencies of p2 þ 2pq þ q2, or
biology, and, in particular, highlighted the importance of numerically as 25(MM) þ 50(MN) þ 25(NN), exactly
TABLE 4.2. Hypothetical frequencies for applying

been called the breeding (effective) population. The
the Hardy–Weinberg Equilibrium test. number of breeding adults has been approximated to
be about one-third of the total population census, with
Genotype MM MN NN Total
prereproductive (children) and postreproductive (eld-
Frequency 9 42 49 100 persons erly) segments comprising the remainder. In more
formal terms, breeding population is defined in popu-
lation genetics as “effective population size.” The
the same genotype proportions observed. What would effective population number is more accurately esti-
be the result if, instead, the sample had yielded geno- mated through derived formulas that generally reach
typic frequencies shown in Table 4.2? Are these pro- lower values than the number of breeding adults due to
portions in H-W equilibrium? such variables as relatedness among individuals, sib-
Testing for H-W equilibrium follows these basic ship size variation, sex ratio imbalance, and the rela-
steps: tive stability of population size. A critical consideration
here is how all of these variables can affect the amount
Step 1 Calculate allele frequencies from the Observed
of genetic variation that is available for evolutionary
genotypic frequencies:
processes to act upon. This matter has particular rele-
pðMÞ ¼ 9 þ 21=100 ¼ 0:3 and qðNÞ ¼ 21 þ 49=100 ¼ 0:7: vance to our upcoming discussion of random genetic
drift, a process that is greatly enhanced by small popu-
Step 2 Calculate Expected genotypic frequencies from
lation size. An additional note here is that gene pool
allele frequencies:
will be used when designating the complete genetic
ð0:3 þ 0:7Þ2 ¼ 0:9 þ 0:42 þ 0:49 or MM ¼ 9MN ¼ 42NN makeup of a population. Furthermore, it should be
realized that field research studies most often will be
¼ 49 persons:
based upon samples of populations and, therefore,
Step 3 Compare Expected with Observed frequencies. may not faithfully reflect the actual variation con-
tained in the total gene pool.
In Table 4.2, Observed genotypic frequencies do match
the Expected frequencies. However, if they did not, then
we would employ a statistical test to ascertain the signifi- Random mating
cance of the difference between them.
What appears to be another stipulation that cannot be
Step 4 Do a Chi-square test of proportionality between met for H-W equilibrium to be present in natural
Observed and Expected genotype frequencies. populations is that of random mating. Random
Step 5 Interpret test results in light of the conditions mating in a formal sense means that there is an equal
that are needed for H-W equilibrium to be probability of selecting any potential mate from an
present; if H-W equilibrium is not found, then available pool. In spite of some difficulties in precisely
consider which of these conditions appears defining what a pool is, no human groups anywhere
most likely to account for the disruption of on the globe have ever been found to choose mates
the equilibrium. solely on a random basis. We will discuss ways human
mating systems are, in fact, socially and culturally
Now that we have discussed all of the conditions
influenced below. (Also see Chapters 17 and 18 of this
that are necessary for H-W equilibrium to exist, we will
volume for extended discussions of mate choice.) For
work a second problem later where it is not present, and
purposes of conforming to H-W equilibrium, it is
thus will require further interpretation that incorpor-
required that the gene or more precisely the locus,
ates information from the following discussion.
under question be distributed through randomly
mating. The MN blood group can be used here to
illustrate this point. Since very few people know what
FACTORS THAT AFFECT THE HARDY–WEINBERG their MN blood type is, it is highly unlikely that it has
EQUILIBRIUM been used to decide among potential mates. Thus the
MN locus can be said to mate randomly. By extension,
Effective population size
all other such loci undergo random mating if they are
To be sure, no natural population, human or otherwise, not involved with mate choice.
is infinitely large in size, yet H-W has often been found
when various human groups were tested. Even so,
Departures from random mating of individuals
caution is certainly in order whenever H-W results are
interpreted for populations with less than hundreds Before proceeding, we will provide some background
of individuals. This caution is especially warranted on mating systems that do not conform to random
because evolution expressed as differential fertility does mating, namely, inbreeding and assortative mating.
not act on a population as a whole but on what has Inbreeding refers to matings between persons who
are genetically related to one another more closely than MM genotype based on first-cousin matings can be
chance, i.e., siblings, first cousins, and so on. Some determined by the following formula:
societies have engaged in systematic forms of close-
relative inbreeding, such as the royal families of Egypt PMM ¼ pM F þ p2M ð1 FÞ
and Britain. Ethnographers have reported on preferred
mating systems between cross-cousins, that is, cousins In this first-cousin example, 1/16 of the loci are pre-
who are related from a son through to his father0 s dicted to be autozygous. Stated in an equivalent
sister0 s daughter, or a son through to his mother0 s manner, the chances of randomly selecting an autozy-
brother0 s daughter in many societies in forming kin- gous locus in offspring of first cousins is 1/16. Very
ship alliances (Levi-Strauss, 1969). In this instance of important to our discussion is that there is an increased
cousin marriages, a certain proportion of the geno- proportion of homozygosity under inbreeding in com-
types found in offspring of these unions can be parison with random mating. This, of course, disrupts
expected to be not only homozygous, but also autozy- H-W equilibrium and leads to a loss of genetic variation.
gous. Autozygous genotypes contain alleles that are In addition, increased homozygosity may have an
Identical by Descent or different copies of the same evolutionary consequence whenever selection has an
allele, by virtue of being inherited from a common opportunity to act against harmful recessive genotypes.
ancestor through pedigree pathways. These pathways However, inbreeding per se does not change allele fre-
are used to calculate an inbreeding coefficient which quencies, it only redistributes alleles into homozygote
then can be used for estimating the proportion of loci classes and away from heterozygotes.
that are expected to be autozygous due to inbreeding. It is presumed that inbreeding is harmful due to an
We will use cousin matings to illustrate these cal- increased likelihood of exposing relatively rare recessive
culations. The inbreeding coefficient formula for gen- alleles that can cause birth defects and generally be det-
eral application is: rimental to normal growth and health. This situation has
X been termed inbreeding depression. In population gen-
Fx ¼ ½ð1=2Þn ð1 þ FA Þ etics, the consequences of inbreeding that lead to a loss
where n is the number of individuals in a common of average fitness make up part of what is known as the
ancestor pathway summed over all paths, and FA is genetic load. The theory of genetic load was developed by
the inbreeding coefficient for the final ancestor in Crow and Kumira (1963) and has been studied in
each path. Figure 4.8 shows a pedigree representing number of human populations. For illustration pur-
first-cousin matings; applying the above formula poses, we will discuss a report by McKusick et al.
yields: (1971) here. In this study, they investigated several sub-
groups of Old Order Amish, a religious sect composed of
Fx ¼ ð1=2Þ5 þ ð1=2Þ5 ¼ 0:0625 or 1=16: farming communities located from Pennsylvania to Indi-
ana. The communities are rural and somewhat isolated,
Referring once again to the MN blood group, the
and have small memberships and practice endogamy,
proportion of loci that are expected to be of autozygous
which makes them closed to outsiders. These social con-
ditions raised the degree of relatedness among individ-
Path diagram Genealogy uals which, in turn, meant higher inbreeding levels. The
A B I A B study reported the presence of several rare genetic dis-
orders, five of them inherited as autosomal recessives,
and two as autosomal dominants. Accompanying pedi-
II C D grees documented the transmission of the disorders
C D through successive generations.
III E F The adverse genetic consequences noted above form
a major rationale that prompted societal attempts to
IV X
disallow close-relative matings through various
E F
inbreeding avoidance practices that might be informal
E and F are related and the common
or more institutionalized through marriage rules. For
ancestors for E and F are A and B
instance, many US states prohibit marriages between
A and B are not inbred
persons who are cousins, or require the cousins to be
X Possible routes between E and F
over common ancestor
beyond a certain age before marrying. Conversely, there
has also been a recent discussion on whether these
E-C-A-D-F n = 5
E-C-B-D-F n = 5 marriage restrictions regarding related persons need
4.8. Pedigree and path diagram of offspring from a first-cousin
to be revised or even repealed (Paul and Spencer, 2008).
mating. From http://www.husdyr.kvl.dk/htm/kc/popgen/genetics/ Assortative mating is another major departure
4/2.htm. from random mating of individuals. It appears in two
forms, positive assortative mating (or homogamy), MICROEVOLUTIONARY PROCESSES

when phenotypes of mated pairs are more similar than OF ALLELE FREQUENCY CHANGE
would be expected under random mating, and negative
assortative mating (or heterogamy), in which the The crux for testing for H-W equilibrium is that it assists
mated pairs are more dissimilar than they would be us in knowing whether or not evolution is occurring, and
under random mating. As is probably obvious to even can further point to the agent of gene frequency change
the most casual observer, humans have a strong ten- should H-W equilibrium not be present. The four such
dency to choose mates like themselves in several evolutionary processes or agents of change are natural
respects, such as sharing cultural traits of language selection, mutation, gene drift, and gene flow, to which
and religion or biological traits of age and stature. can be added recombination and population structure as
The last-cited trait is of further interest in that, for factors or variables that can facilitate the action of all of
many societies, there is a “male taller norm” that char- these processes. (The reader is reminded that Chapter 1
acterizes unions (Gillis and Avis, 1980). of this volume covered this material in depth, so the
Documentation of negative assortative mating has purpose here is to fill out some of that discussion with
been scarce and contradictory. One such study dealt examples taken from human biology studies.)
with the Hutterites, a religious community residing in For the sake of simplicity, two fundamental state-
North America. In investigating their human leukocyte ments of evolution can be written, first as depicting the
antigen (HLA) genotypes, researchers found evidence essence of Darwinian thinking and then according to a
indicating that there was an avoidance of marriages Modern Synthesis viewpoint, each shown in Figure 4.9.
between persons possessing the same genotypes (Ober These formulations demonstrate the nature of sci-
et al., 1997). However, a similar study done on South entific advance in which the profound new discovery
American Indian tribes failed to find this form of non- made by Darwin has been added to and refined
random mating pattern for HLA genotypes (Hedrick through continued research. We can now proceed to
and Black, 1997). An accompanying invited editorial discuss important aspects of microevolution that
comment on these two conflicting studies (Beauchamp underlie the formulations.
and Yamazaki, 1997) recommended that continued
research be done to resolve what they determined to
be a clearly plausible explanation for why great vari- EVOLUTIONARY SOURCES OF GENETIC
ation in HLA genotypes is being maintained in human VARIATION
populations. (See Chapter 13 of this volume for more
Mutation
discussion of the HLA system.)
Assortative mating pertains to specific phenotypic A primary source of new genetic material is mutation.
traits, usually of multifactorial inheritance, which, Of potential evolutionary significance, point mutations
unlike inbreeding, can affect any of the entire genome of nucleotides (substitutions, insertions, deletions of
simultaneously in terms of similar genotypes. Further- base-pairs) have been shown to be highly relevant. An
more, similar to inbreeding, positive assortative mating oft-cited example of the evolutionary importance of
likely leads to an increase in proportion of homozy- mutations is human hemoglobin whereby a point
gotes; however, in contrast to inbreeding, this results mutation on one of the molecular chains (beta) making
in increasing the variance within a population due to up the protein offered a selective advantage to persons
the formation of more distinct phenotypic grouping of carrying the sickle cell trait when they were exposed to
individuals. For instance, tall and short stature tends to malarial infection, as will be discussed shortly. How-
form a bimodal distribution composed of the assorta- ever, most point mutations are found to be neutral to
tively mated pairs. The correlation coefficient is used to the action of selection, while, on the opposite side,
measure the strength of the association for traits or major mutational changes and chromosomal aberra-
variables undergoing assortative mating. This coeffi- tions very likely lead to dire outcomes in terms of
cient is denoted by an r-value which can range from 1 reduced chances for survival and lowering of fertility.
(complete positive correlation) to –1 (complete negative It is sometimes stated that mutations are generally
correlation). In comparing statures for husbands and harmful. This could be clarified to mean that muta-
wives, r-values tend to be in the range of 0.2–0.3, tions usually occur without respect to the adaptive
although, for spouses of female MZ twins, it was found needs of organisms, that is to say they occur randomly.
to be at nearly 0.5 (Meier and Jamison, 1990). Lastly, it Therefore, there is little likelihood that newly arising
should be noted that, like inbreeding, assortative mutations will be beneficial to enhancing either the
mating by itself only changes genotypic frequencies, survival or reproductive outcome of individuals. On
thus upsetting H-W equilibrium, but does not directly the other hand, should the mutational change turn
alter gene frequencies. It is now time to take up this last out to be beneficial, it is then possible for its frequency
point, and examine the forces of evolution. to increase at a rate that is affected by its relative
Darwinian Evolution:
Time + Variation + Natural Selection → Evolutionary adaptation
Modern Synthetic Theory:
Time + Variation + Population + Selection → Evolution

structure
↓ ↓ ↓ ↓
(includes (includes (leads to (as genetic

mutation gene random drift adaptation change in gene
flow and related to- and frequencies
recombination) population extinction) and DNA
size and sequences)
composition)
4.9. Fundamental statements of evolutionary theory.
benefit and whether it is expressed as a dominant or novel genes. While this complicated interplay between
recessive allele. Unfortunately, in the case of bacteria, natural selection and gene flow will be difficult to
certain mutational change that becomes adaptively document, especially for recent human groups (cf.
useful may cause drug resistance because of the over- Gross, 2006), it probably does underlie the successful
use of antibiotics. It might be noted that there has been migration and adaptation that had occurred in much
a discussion in the literature regarding directed or earlier Pleistocene populations (Leonard, 2003).
adaptive mutation, where nucleotide changes may There are also alternate forms of migration, for
not always occur randomly (Hastings et al., 2004; instance, one-way gene flow in which one population
Galhardo et al.,2007). While this idea is highly intri- admixes exclusively with another, or two-way
guing, additional research certainly is needed to verify exchange of genes among two or more groups. Added
that some kind of nonrandom mutation actually occurs. to these forms are the variables of how much differ-
Mutations alter allele frequencies as an existing ence there is between the gene pools involved before
gene is chemically changed. For example, if, in the admixing occurred, and how many individuals partici-
MN blood group discussed above, some M alleles pated in the process adjusted by the relative sizes of the
mutated to N, then the frequency of p(M) would groups involved Considering all of these factors, it
decrease and q(N) would correspondingly increase. becomes apparent that accurately estimating gene flow
Obviously, if the mutation of the N to M allele occurred becomes complex and altogether not very meaningful.
at the same rate (signified as m), there would be a zero There has been an indeterminately long history of
net change in allele frequencies, although evolution human expansions, conquests, and voluntary and
can still said to have taken place. forced movements that represent a complex array of
admixing of once separated peoples. While formulas
have been derived to estimate the amount of admixture
Gene flow
within a human group, major uncertainties regarding
A secondary source of genetic variation arrives through gene frequencies of original parental groups usually
the process of gene flow, otherwise known as admix- raises questions as to the accuracy of these calcula-
ture, or migration (signified as m) of people who inter- tions. An enlightening realization of the long history
breed to some degree with individuals from other of human population movements and intermingling is
groups they encounter. There are many variables and that any attempts at racial classification become highly
obstacles that make gene flow selective to certain arbitrary (See Chapter 15 of this volume for a full
groups and individuals within groups, all of which discussion of this and other matters pertinent to study-
can affect gene frequencies. One of these is that per- ing the nature of human variation.)
sons who migrate tend to be in a better state of health Once again, just using the MN blood group, gene
than those who are not so able. Then, if mobility was in flow alters allele frequencies. If, for example, a popula-
part attributable to genetic variants unique to the tion high in genotype MM admixes with another high
migrants, a consequence will be the spread of these in NN, then this process produces an elevated
proportion of MN genotypes, which, in turn, disrupts population genetics theory, drift is considered most
H-W equilibrium. Overall, the gene flow process effective whenever the mutation rate (m), net migra-
becomes highly relevant in the context of investigating tion/gene flow rate (m) and the selection coefficient
population history and structure, which has been a (s) < 1/2N, where N is the population size. In particular,
focused interest within the field known as anthropo- for those loci that are selectively neutral, it is expected
logical genetics. Results of some of this research are that random drift will be the primary agent of change in
summarized in Chapter 13 of this volume. frequency. As will be seen in Chapter 14 of this volume,
allelic frequencies at neutral loci are decidedly import-
ant in studying human population genetic relationships
EVOLUTIONARY PROCESSES ACTING and in constructing phylogenetic trees.
UPON VARIATION Genetic drift has been described and, at times,
documented in gene frequency analysis for extant
The remaining two processes, random genetic drift and human populations that had experienced sampling
natural selection, are active in changing allele frequen- error episodes in their histories. One of these circum-
cies and can lead, in the case of genetic drift, to a loss stances involves a small group of migrants founding a
of variation, while selection can result in a loss, an new community (“founder effect”) and another reflects
increase or even maintain a stable level of genetic vari- a markedly reduced number of survivors following a
ation. We will look at genetic drift first. catastrophe (“survivorship effect”). In either case, the
newly formed group does not accurately represent the
genetic variation that had been present in the parent
Random genetic drift
population from which it was derived. Crucial for
Random genetic drift is basically sampling error due to assigning genetic drift as a cause, this change has to
small numbers. Hence, its effect is strongest in popula- be attributable to random processes.
tions having small effective size. Drift is the opposite of The founder effect or principle probably has been
random sampling that is expected to be representative cited most often, as in the case of reconstructing the
of the variation that exists in sampled populations. effective population size and genetic makeup of the
Instead, random here refers to the unpredictability of earliest migrant groups to the New World (Hey,
the direction of gene frequency change in the short 2005). Founder effect has also been employed to
term, say over each successive generation. A graph of explain unusual gene frequencies observed in religious
genetic drift shows fluctuating frequencies of a single isolates, which will be discussed below to illustrate the
allele (Figure 4.10). essential features of genetic drift.
Ultimately, over many generations, there is a ten- A religious isolate refers to a community that main-
dency for allele frequencies to drift toward the loss of tains strict within-group marriage rules, that is, the
one allele and the corresponding fixation of the other practice of endogamy is required. This, of course,
allele. This, of course, results in a reduction in genetic means that gene flow from outside would not influence
variation. The time to fixation will be dependent upon gene frequency distributions. Beginning in the late
the size of the population and how significant the other 1940s, a number of these religious communities have
evolutionary processes are with regard to the locus been studied with regard to genetic drift, and from that
under study. As a summarizing statement within time period there appeared a classic example. Glass
et al. (1952) conducted their research among the Old
1 Order “Dunker” (Old Order German Baptist Brethren)
living in Franklin County, Pennsylvania. This commu-
nity has its origins in Rhineland, Germany, and des-
cended from a small number of founding migrants
P who came to America about 200 years ago. The
researchers investigated several genetic traits, includ-
ing the major blood groups. Since we have been refer-
ring to the MN blood group, that system can serve as
our reference point. The pertinent findings are that the
0
0 2500 frequency of the M allele in the Dunker Isolate was
Generations p(M) ¼ 0.655, while, in the comparative groups, it was
4.10. Fluctuating allele frequency simulating random genetic p(M) ¼ 0.548 in West Germany, and p(M) ¼ 0.540 for
drift in a population of 1000 individuals. The allele frequency,
the United States. Of course, q(N) would just be 1–p.
designated as p along the y-axis, begins at about 0.5 before
reaching fixation over the course of more than 1750 generations, The genotypic frequency differences between the
as plotted on the x-axis. From http://darwin.eeb.uconn.edu/ Dunker Isolate and the other two groups were highly
simulations/drift.html. significant. There is naturally some concern whether
these comparative samples are truly representative of discussion concerning evolution, that is, natural selec-
especially the US population, but, at face value, they tion. Darwin0 s theory is that the underlying force that
clearly suggest that the founder Dunker Isolate had explains adaptive change within evolutionary lines,
diverged genetically from its source population in West and diversification and speciation between lines, is
Germany, and had not converged upon the US sample. selection. Natural selection has been thoroughly tested
The other genetic traits under study generally con- and overwhelmingly confirmed over the past century
firmed these findings. As for interpretation, after and a half. Darwin0 s prediction that “[m]uch light
ruling out any real likelihood of selection acting at would be thrown . . .” [on human evolution] (Darwin,
the MN locus, the authors concluded that these results 1892, p. 304) has been fully realized. While this chapter
are most likely attributable to genetic drift. As another deals only with some highlights of evolutionary genet-
example of founder effect, it has been reported in a ics applied to humans, the reader will find that this
study done in Quebec, Canada, that this kind of demo- volume as a whole is replete in its coverage of natural
graphic event accounted for 85% of cases of the rare selection outcomes within our species.
mitochrondrial disease called Leber hereditary optic Of the many forms that selection can take (see
neuropathy (LHON), a disorder that was mentioned Chapter 1 of this volume for a complete discussion of
earlier (Laberge et al., 2005). these, and other chapters for topical applications of
Survivorship effect probably has been repeated selection theory), this section will focus on only two,
untold times throughout human history, and indeed directional and balancing selection pertaining to single
population “bottlenecks,” due to sharply reduced locus, and two segregating allele systems. Again, there
numbers caused by loss of life, or due to small group will be examples drawn from human biology research.
migration of founders as described above, form a major
point of reference for tracing our species0 Pleistocene
Directional selection
origins (for a review see Hawks et al., 2000). As an
example from a recent time period, Roberts (1971) Initially, we will use the MN blood group to illustrate
reported on an isolated island population in the south selection and related concepts in a hypothetical case.
Atlantic, Tristan da Cunha, originally settled by a small Say that for whatever reason, persons possessing the
number of founders in the nineteenth century, subse- MM genotype had a selective advantage over the other
quently experienced two episodes of population bottle- two genotypes, MN and NN. By this we mean that MM
necks over approximately a century. Through some individuals had either a greater likelihood of surviving
careful tracing of pedigrees, and scouring records per- or having a higher reproductive success, or both. What
taining to migration to and from the island, he was able would be expected over time is that the frequency of the
to ascertain the relative genetic contributions (differen- M allele would increase relative to the N allele, and,
tial reproduction) of island members up to the time of the hence, the direction of systematic change would be shift
study in 1961. Some were much more prolific than toward fixing the M allele and losing of the N allele.
others. Of considerable interest here is that, while at least However, that tendency is mediated by the extent of
one of the bottleneck reductions was deemed to be due to the differential between the three genotypes that can
sheer accident, and likely therefore to be relegated as be measured in terms of their respective fitnesses.
contributing toward genetic drift, the other earlier bottle- For this calculation, fitness refers to genotypic
neck could well have led to loss of genetic variation in the reproductive success, and of course, to have survived
remaining gene pool by selective migration of certain to sexual maturity. Fitness can be denoted as w, while,
families. In both cases, marked population reduction on the opposite side of the ledger, the selection coeffi-
likely lead to increased levels of inbreeding in this small, cient is designated as s, such that w þ s ¼ 1. At the
highly isolated island community, and as a consequence extremes in the range of these values, when w ¼ 1, this
elevated the risk of exposing genetic diseases. There had would designate an optimal genotype for the existing
been outbreaks of respiratory diseases on Tristan da environmental conditions. Conversely, whenever s ¼ 1,
Cunha, which lead a research team to search for a gen- this genotype is lethal both in the sense of mortality or
etic basis of asthma in a setting (founder and survivor- sterility, and, in either instance, does not contribute
ship effects, and inbreeding) thought to be conducive for genetically to the next generation.
localizing genes (Zamel et al., 1996). The results from Table 4.3 presents an example of selection acting
this study did support a major gene involvement in the against the dominant genotypes which results in direc-
expression of asthma. tional change in allele frequencies. This is sometimes
referred to as negative selection since it acts to remove
deleterious alleles.
Selection
Achondroplasia is a form of dwarfism character-
The last of the evolutionary processes to cover is the ized by reduced limb growth but normal proportions
one that undoubtedly ranks at the forefront of any of the torso. It results from an autosomal dominant
TABLE 4.3. Selection against the dominant using TABLE 4.4. Heterozygote advantage and balancing
achondroplasia as an example. selection in a malarial environment.
Genotype AA Aa aa Genotype AA AS SS
Relative fitness (w) 0 0.20* 1.00 Advantage – Resistance Resistance

Frequency p2(1–s) 2pq(1–t) q2 to malaria to malaria
Disadvantage Susceptibility – Sickle cell
Note: Selection coefficients are s ¼ 1.00 and t ¼ 0.80. to malaria anemia
*This fitness value was taken from Bodmer and Cavalli-Sforza,
1976. Relative 1–s 1 1–t
Fitness
Frequency p2(1–s) 2pq(1) q2(1–t)
point mutation (substitution of arginine for glycine) in Note: Selection coefficients are s ¼ 0.12 and t ¼ 0.86 based
on estimates taken from Bodmer and Cavalli-Sforza (1976).
the fibroblast growth factor receptor gene (FGFR3,
located on the short arm of chromosome 4) that leads
to shortening of the long bones of arms and legs. About
80% of cases are the result of sporadic new mutations
with some evidence for paternal age effect. shown to be implicated in human groups living in
From Table 4.3 it can be seen that AA and Aa have endemic malarial regions. A more complete story of
reduced fitnesses in comparison with aa. Unfortu- this connection can be found in Chapters 13, 14, and
nately, the homozygous AA genotype is either stillborn 27 of this volume. Here, we focus upon the model of
or lives for only a short period following birth. On the selection for the heterozygote to illustrate some basic
other hand, the heterozygote Aa generally has a normal points regarding population genetics. Table 4.4 lays
life span. Their reduced fitness is not due to fertility out a framework of this mode of selection, involving a
problems but to social or cultural conditions that impli- single locus, with two alleles, A and S.
cate constraints on finding available marriage partners. It can be seen that genotypes AA and SS are at a
From a microevolutionary perspective, fitness disadvantage for separate reasons, while AS heterozy-
values and selection coefficients in Table 4.3 indicate gotes enjoy an advantage on the grounds that they have
that, over generations, there will be a reduction in the a functional level of normal hemoglobin and are also
dominant allele A, with a corresponding increase in a. resistant to malaria. Historical empirical data are
There are equations used in population genetics to available to demonstrate just how much this advantage
estimate the rate of gene frequency change due to meant in terms of survivorship to adulthood in an
directional selection, and also models for predicting African group, the Yorubas, from Nigeria, in terms of
an equilibrium, say, between selection and mutation. selection coefficient estimates found in Table 4.4. Con-
We will cover that model a little later on. verting these estimates into fitness values means that,
Modeling of directional evolutionary change for when the study was conducted some 40 years ago, for
polygenic traits having adaptive value is not so precise, every 100 surviving AS heterozygotes, 88 AA individ-
simply because the loci involved generally are not uals lived to adulthood, while only 14 were SS sur-
known, and as we discussed earlier, these traits are sub- vivors. Given this differential selection process, the S
ject to multiple environmental interactions. For allele is expected to rapidly decrease, but of course, it
instance, the major trend of increasing brain size won0 t entirely disappear because of the counter selec-
throughout early human evolution is clearly demon- tion against the A allele of the other homozygote class.
strable under a positive direction selection model, and These opposing selective forces could lead to an equi-
presumed to be the result of expanding brains for evolu- librium whereby allele frequencies no longer change
tionary success. Even though it is not possible to be very but are maintained as a balanced polymorphism, so
specific with regard to the genetic basis of this change, a long as environmental conditions remain fairly stable
possible breakthrough has occurred recently (Evans and no other evolutionary forces are operating. Under
et al., 2005; Mekel-Bobrov et al., 2005), yet this discovery these assumptions, the frequency of the S allele will
also has been questioned (Timpson et al., 2007). attain equilibrium according to the following formula:
q
^ ¼ s=s þ t, or numerically as: q ^ ¼ 0:12=0:12 þ 0:86 ¼
0:122. The S allele would then be maintained in the
Balancing selection
gene pool at about the level of 12%, if conditions
We now shift to another selection model that has remained fairly constant. This means, for example,
received considerable attention in human biology, bal- that the level of malarial stress did not change, and
ancing selection, in which the heterozygote genotype there were no interactions with other evolution pro-
maintains an advantage over homozygote forms. This, cesses, such as gene flow from outside the region. Of
of course, includes the sickle cell locus that has been historical significance, the S allele has increased in
TABLE 4.5. Test of the Hardy–Weinberg Equilibrium.

that natural populations are very likely subjected
to interacting forces.
Genotype MM MN NN Total
Observed frequency 10 80 10 100 persons Selection and mutation

Allele frequency p(M) ¼ 0.5 and q(N) ¼ 0.5
Expected frequency 25 50 25 100 persons The most obvious of these might be selection acting as a
Obs – Exp –15 30 –15 filtering agent to remove deleterious mutations, at a
(Obs – Exp)2/Obs 9 18 9
rate dependent upon whether the mutation is expressed
P as a dominant or recessive, and then depending how
Chi-square (x2) ¼ [(Obs Exp)2/Obs] ¼ 36
harmful the mutation is, that is, how severe the selec-
tion coefficient is. Considering these variables, an equi-
librium of allele frequencies between selection and
frequency in generations of African-Americans des- mutation can be reached. This equilibrium can be
cended from ancestors who were slaves, due in part expressed in the formula, p ^ ¼ =s. For an extreme
to relaxation of selection constraints and reduced mal- example, newly arising mutations that are lethal auto-
arial disease stress in the New World (Cavalli-Sforza somal dominants would be restricted to a frequency of
and Bodmer, 1999). that of their mutation rate, since they would be elimin-
ated as soon as they appeared in each generation. In the
case of achondroplasia presented above, an equlibrium
The Hardy–Weinberg test
value would be: p ^ ¼ 0:00001=0:8 ¼ 0:0000125, or only
Now that we have described all of the factors that can slighter higher than the mutation rate because of the
alter genotypic frequencies, and also microevolution- marked selection coefficient. Of course, this calculation
ary processes that change gene frequencies, we can do only considers the interaction of mutation and selec-
a test for the H-W equilibrium, following the steps tion, while other factors may also be involved and alter
outlined earlier (Table 4.5). the estimate.
With this x2 value, a probability table in a standard
statistics textbook can be consulted, and it would be
Selection and genetic drift
found that this is a highly significant finding. Hence, it
would lead to a justifiable conclusion that H-W equi- A second kind of interaction takes place between selec-
librium was not present in this sample. Therefore, it is tion and genetic drift. To a certain degree, it can be
appropriate to consider which of the equilibrium con- argued that selection and drift are mutually exclusive
ditions were not met. Note that in this sample there is a forces, one being systematic and the other random. In
marked deficiency of homozygotes and a correspond- more formal population genetic terminology, this dis-
ing high gain in heterozygotes. What could account for tinction is sometimes expressed as the difference
this pattern? between deterministic and stochastic processes. As a
We can start with the sample size, which is rela- consequence, drift is most likely to act upon neutral
tively small and thus might be implicated. Then again, loci and not on those genes that are vitally important
the research sampling might well be an accurate deter- for an organism0 s survival and under heavy selection
mination of the makeup of the gene pool, and the pressure. However, when effective population sizes
disproportionality of genotypes is due to a random become drastically reduced, there are opportunities
genetic drift event such as seen in the founder effect. for drift to occur even on genes that are not neutral,
Finally, and perhaps most obviously, heterozygote although they probably also have relatively low selec-
advantage jumps out as a possibility. In this case, add- tion coefficients. An example of genetic drift/selection
itional research is required to demonstrate how selec- interaction was discussed earlier for the island popula-
tion has been operating to bring about an excess tion on Tristan da Cunha.
survival/reproduction of heterozygotes at the detri-
ment of homozygote classes. You will find another
Genetic drift and gene flow
study problem that deals with a test of H-W equilib-
rium at the end of the chapter. Yet a third kind of interaction often occurs between
genetic drift and gene flow. Human populations, par-
ticularly prehistoric groups that resided in small groups
INTERACTION OF MICROEVOLUTIONARY and were dispersed over large areas, were highly prone
PROCESSES to the action of genetic drift and its consequence of loss
of variation. Yet, there were also regular contacts
The above discussion of the four evolutionary pro- among these dispersed groups, and the resultant gene
cesses as separate entities is not entirely realistic in flow would have introduced some genetic variation
back into their gene pools. In this situation, the dual TABLE 4.6. Microevolutionary processes and genetic
action of gene flow with respect to variation is apparent variation.
in that it increases variation into populations that are
receiving the migrants, but, as a consequence, the Genetic variation
amount of genetic difference between the populations
Within
involved with the gene flow process is lessened. As a Process a population Between populations
further consideration, genetic drift may not have been
Mutation Increases Increases
so prominent since population size was effectively
extended beyond each of the local groups. Gene flow Increases Decreases
Genetic drift Decreases Increases
Selection Increases/ Increases/decreases
decreases
SHIFTING BALANCE THEORY
and maintains
variation
This discussion of microevolution and interacting
forces naturally leads to a discussion of the shifting
balance theory wherein all four processes enter into a
coherent, but not universally accepted, model of evolu- critique of (Coyne et al., 2000) or in support of (Wade
tion. For some background, two prominent founders of and Goodenough, 2000) the theory.
population genetics engaged in a heated battle in the As a summing up of this section, Table 4.6 organ-
mid-twentieth century as they offered opposing view- izes how evolutionary processes affect genetic vari-
points concerning the big picture of evolution. One of ation. Please note that selection can yield multiple
them, Sir Ronald A. Fisher (1890–1962), proposed that outcomes with respect to variation.
a species, or at least a large panmictic (random-
mating) population, adapted as a whole through the
selection of combinations of alleles that increased CONCLUSION
overall fitness. In contrast, Sewall Wright (1889–1988)
constructed the shifting balance theory that required a The major aim of this chapter has been to show the
species, or large populations, to be composed of many many ways in which genetics has been incorporated
small, partially isolated breeding units (demes), some into human biological research. We have discussed
of which would evolve to increase average fitness of the four areas of genetics, namely, Mendelian, non-
total population, while the others would be replaced by Mendelian, molecular, and population or evolutionary
these more successful demes. Random genetic drift, genetics. Also included in this discussion were
and its attendant nature of producing, by chance, novel examples of studies that were mainly conducted with
genotypic combinations of alleles and genotypes, an eye toward understanding genetic variation, most
played an essential role in the shifting balance theory. notably in the context of microevolutionary processes
The theory takes its name by explaining how a one- of mutation, gene flow, random drift, and selection.
time balance of genotypic combinations can be shifted Along the way, we indicated topics that have been
to a new and more fit combination as likely demanded addressed in other chapters of the book. The reader is
in a varied landscape of adaptive requirements, and if encouraged to seek out these topics in order to gain an
evolution of the population is to continue. enhanced appreciation for the central role that genet-
An alternative of course is extinction. Reduced to its ics has played in human biology.
essentials, this shifting balance originates with muta-
tions taking place in an array of demes, randomly
resulting in new combinations only a few of which DISCUSSION POINTS
become selectively advantageous. Thus, reproductive
success that leads to population growth which then pro- 1. What exactly is meant by the term “recombination”
motes migration into areas occupied by other less suc- in generating genetic variation?
cessful deme will replace them in part via gene flow. This 2. What are the major similarities and differences
discussion very briefly describes the process of inter- between monogenic and polygenic inheritance? Dis-
demic selection as proposed by Sewall Wright (1969). cuss what you think would be the evolutionary
A succinct review of the shifting balance theory can impact on traits that are Mendelian versus polygenic.
be found in Crow (1986), a colleague of Wright0 s at the 3. Define the following in terms of function, give a
University of Wisconsin-Madison. Crow considered brief description of biochemistry and/or structural
that both Wright and Fisher may have been correct components, and briefly describe the relationships
on some points while, in more recent discussions of between them: chromosome, gene, gene product,
the matter, sides are still being drawn, either in amino acid, protein.
Cavalli-Sforza, L. L. and Bodmer, W. F. (1999). The Genetics

TABLE 4.7. Sample genotypic distribution.
of Human Populations. Mineola, NY: Dover Publications.
MM MN NN Total Cedar, H. and Bergman, Y. (2009). Linking DNA methyla-
tion and histone modification: patterns and paradigms.
20 25 75 120 persons
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5 Demography
James Holland Jones
INTRODUCTION that we simultaneously monitor male and female seg-

ments of the population. Human male and female life
Demography lies at the heart of every statement about cycles are, indeed, quite different. For example, while
selection. Fitness is generally understood to be the more boys are born on average than girls, males
relative proportion that an individual unit contributes experience higher mortality rates throughout life.
to a population of such units. These populations could Men typically begin reproduction later than women,
easily be of individuals, genes, or even groups. The way but can continue reproducing after women cease
that a unit comes to make a larger contribution to a reproduction. While such observations suggest that
population is to have a growth rate greater than that of modeling both sexes would be important, a common
competitors, leading to a more technical definition of demographic conceit is to focus attention on the
fitness as the instantaneous rate of increase. Since female segment of the population and assume what is
fitness is a growth rate, considerations of the size and known as “female demographic dominance.” The idea
composition of population – i.e., demographic consid- behind female demographic dominance is that women
erations – are central to any evolutionary story. Life are, in essence, the rate-limiting factor for reproduc-
history theory is the evolutionary study of the major tion. One-sex models are mathematically simpler and
events of the life cycle. It is the body of theory that manage to capture a remarkable amount of the
explains why characteristics such as life span, age at variation that exists in human populations.
maturity, and the tempo and duration of reproduction The environment, whether natural, social, or other-
vary between species. Life history theory is intimately wise human-constructed, is not constant. When birth,
related to demography as explaining the age pattern of death, and migration rates depend on environmental
reproductive investments – what Schaffer (1983) refers inputs (e.g., mortality rates may be high during a
to as “the general life history problem” – is a funda- drought or hard winter), these rates will vary overtime.
mentally demographic question. Furthermore, populations of anthropological interest
In this chapter, I will focus the discussion on are frequently small and so we should expect a
formal demography, the collection of mathematical considerable amount of variation (i.e., “error”) in our
and statistical tools for enumerating populations, demographic measurements that results simply from
measuring their vital rates (i.e., rates of birth, death, sampling and finite-population effects. These observa-
and marriage) and related quantities, and projecting tions suggest that stochastic models – models that
how they will change in structure, size, and compos- account for the varying nature of demographic rates –
ition. These same tools, which were largely developed are necessary for understanding human populations
by social scientists, appear repeatedly in the ecological (Jones, 2005). However, stochastic population models
and evolutionary literature. For example, the formal- are much more mathematically complicated than
ism linking birth and death rates to population deterministic models that assume constant rates, and
structure and the population rate of increase also stochastic models ultimately take as their foundation
happens to define fitness in an age-structured popula- deterministic models. In this chapter, I will therefore
tion (Charlesworth, 1994). This formalism will be dis- focus on one-sex deterministic population models.
cussed extensively in “The Euler–Lotka characteristic A number of excellent demography textbooks cur-
equation” section below. rently exist for the reader interested in pursuing
Humans are dioecious organisms requiring the this material further. Preston et al. (2001) is a fairly
successful union of the gametes of both male and complete introductory text in formal demography,
female to reproduce. As such, a full accounting of with a focus on the analysis of large state-level
human reproduction and population renewal requires populations. Hinde (1998) is a somewhat more basic
74
Demography 75
introduction while Siegel and Swanson (2004) provide a Rearranging Equation 5.1 and integrating to solve
quite complete reference on demographic methods. for N(t), the size of the population at time t, we see that
Keyfitz and Caswell (2005) is the third edition of
NðtÞ ¼ Nð0Þert ; ð5:2Þ
Keyfitz’s classic text on applied mathematical demo-
graphy and is written at a more advanced level. The where N(0) is the initial population size.
comprehensive reference for matrix population models Dividing both sides by N(0), we see that the ratio of
is Caswell (2001). population sizes t years apart is ert and the ratio of
I begin in the “Exponential growth” section below by population sizes one year apart will be er. To solve for
reviewing the basic features of populations that grow at the doubling time of a population, substitute N(t) ¼ 2
a constant rate in continuous time. Exponential and N(0) ¼ 1 and we see that t ¼ log(2)/r, where the all
population increase is fundamental to much of the for- logarithms are assumed to the base e (i.e., natural
malism of demography. In the following “The life table” logarithms). Since log(2) 0.69, this yields the heuris-
section, I introduce the life table, a scheme for repre- tic that the doubling time of a population growing r
senting the mortality experience of an age-structured percent annually is approximately 70/r. A population
population. Life table analysis lies at the heart of growing 2% annually has a doubling time of approxi-
demography and probably represents the bulk of mately 35 years (and a tripling time of 55 years).
anthropological applications of demographic tech- We can also use the exponential growth equation to
niques. One important subset of life table analysis is estimate the growth rate of a population if we have
the use of model schedules of mortality, which is also available censuses at two separate times. Without loss
reviewed. In “Fertility” section below, I discuss methods of generality, call the population size at the first census
for the analysis of fertility. In the following “The Euler– N0 and the population size at the second census Nt. The
Lotka characteristic equation” section, I introduce the estimated growth rate is simply
stable population model. This model links the major
logðNt Þ logðN0 Þ
features of demography – age-specific schedules of ^r ¼ ð5:3Þ
t
mortality and reproduction, age-structure, and the
growth rate – into a single formalism. In addition to For example, Goodall (1986) tabulates population
being an elegant representation of the demography of counts of the Kasakela community of chimpanzees
populations, the stable model can be used to help model for the Gombe National Park, Tanzania. In 1965, she
populations lacking vital-event registration or where counted a total of 51 individuals summed across all
demographic data are incomplete or missing. Any set stage/sex classes, while there were 36 total individuals
of tools that help with missing data must be useful in the Kasekela community in 1983. This leads to an
for anthropology. In the “Population projection: matrix estimated growth rate of ^r ¼ 0:019, a decline of
models” section below, I introduce population projec- nearly 2% annually. This summary measure hides a
tion methods and evolutionary demography. The same great deal of complexity, including a serious epidemic
formalism that allows us to project age-structured and the fissioning of the community, but this is the
populations forward in time also helps us understand nature of simple summary measures of complex
how selection shapes the life cycle. phenomena.
EXPONENTIAL GROWTH THE LIFE TABLE
A population closed to immigration and emigration, in The life table is a means of representing the mortality
which births and deaths can happen at any time and experience of a population. It takes as its object of
the rates of births and deaths are constant, will grow at study a hypothetical cohort (i.e., a group of people
a rate r ¼ b d, where b is the per capita number of born at the same moment) that is closed to migration.
births in a unit of time and d is the per capita number This cohort is followed through time until every one of
of deaths. This growth rate is the per capita, instantan- its members die. In reality, we are rarely faced with
eous rate of increase of the population: analyzing the mortality experience of a true cohort.
The data that we collect typically come from a
1 dN particular period and represent a cross-section of the
r¼ ; ð5:1Þ
N dt population in a particular moment in time. Many of
where N is the size of the population. It is worth the mathematical and statistical techniques surround-
noting here that, by definition, this also means that ing the life table involve translating the observed
r ¼ d log N(t)/dt. That is, the rate of increase of a popu- period data into a synthetic cohort that can be
lation is equal to the rate of change in the natural analyzed. The distinction between period and cohort
logarithm of the population size. is fundamental in demography. In general, we can only
76 James Holland Jones
analyze cohort measures retrospectively. The majority 20–24. In human demography, it is usual to set n ¼ 5
of anthropological applications will be based on for all ages greater than x ¼ 5. As mortality changes
period measures. This arises, as much as anything, very rapidly in the first five years of life, most analyses
because of the typically small samples available in of human mortality break the first five years into two
anthropological populations. age classes, the first lasting one year and the second
A graphical device that helps to keep the concepts lasting four years. Thus, it is standard in human
of period and cohort – really between calendar time demography for x to include the classes 0, 1–4, 5–9,
and age – straight is the Lexis diagram. In a Lexis 10–14, . . . The five-year age classes are known as
diagram, the horizontal axis represents calendar time, quinquennia. All deaths beyond a certain age are typic-
while the vertical axis represents age. A person who is ally lumped together and that last age class is open
born at some time t is plotted with a lifeline that (i.e., n ¼ 1). This last open age class has historically
intercepts the horizontal axis at t and then increases been 85 years for state level societies with vital event
with a slope of unity until death. Consider the Lexis registration systems. However, the drastic reduction in
diagram in Figure 5.1. It spans the period between old-age mortality has led to vital-event tabulations
1960 and 1970, in which 5 births, labeled 1–5, occur. being extended to ages as old as 110. Life tables
Individuals 2, 3, and 5 survive to the end of the constructed for age class where n > 1 are known as
observed period, whereas individuals 1 and 4 die in abridged life tables.
their 6th and 3rd years respectively (i.e., having The data underlying the life table are the number
reached the exact ages of 5 and 2). of observed deaths by age and the population at risk
Mortality, like many other features of the human for death in those ages. If we assume that the popula-
life cycle, changes systematically with age and an tion is closed to net migration, then the mid-interval
adequate description of the mortality experience of a population size represents an adequate measure of
human population should attempt to reduce the units exposure to risk. The estimate of the mortality rate
being described to be as homogeneous as possible. For for any age x is therefore n Mx ¼ n dx =n Kx . Continuing
the rest of this chapter, I will assume that we are with the example of 20-year-olds in Madagascar, the
dealing with an age-structured population. That is, number of deaths in 1966 to women ages 20 to 24 was
we keep track of the size and changes that happen to 3162, for a central mortality rate of 0.014. The
the population classified by an exhaustive set of age quantity nMx is an empirical estimator for what is
categories. Begin by defining a series of nonoverlap- known as the period central death rate of the popula-
ping age classes, x of width n. In the standard notation tion. It is important to note that this is a rate and not
of demography a measure of interest is subscripted by a probability of death in an interval. The central death
its age, x and presubscripted by the width of that inter- rate is directly analogous to the growth rate of a
val n. For a life cycle with k age-classes, n could con- population, r, discussed in the above “Exponential
ceivably be a vector of length k specifying different age- growth” section. In particular, it is the per capita rate
class widths. Let the mid-interval population size for of decrease (whereas r is usually the per capita rate of
age-class x be nKx. For example, in Madagascar increase) and it applies only to a cohort. In order to
in 1966, there were 5K20 ¼ 225 887 women alive aged proceed with the construction of a life table, we need
to convert the mortality rates to probabilities. The key
ingredient for this conversion is the nax schedule,
10 where nax denotes the number of person-years
lived by individuals dying between ages x and x þ n.
Let nqx denote the probability of dying in the interval
8
2 [x,x þ n).1 The Greville equation states that, given an
3 estimate of the central death rate, nmx (typically the
6 observed death rate nMx), the conversion from nMx
1 and nqx is given by:
Age
4 n n Mx
n qx ¼ : ð5:4Þ
1 þ n Mx ðn n ax Þ
4
2
5 1
The notation [x, x þ n) indicates that for some age y in the
0 interval x y < x þ n. That is, it includes exact age x but
1960 1962 1964 1966 1968 1970 not exact age x þ n, which is in the next interval. Thus
the 5-year age interval beginning at the exact age of 20
Calendar time
includes individuals who were aged 20–24 on their last
5.1. An example of a Lexis diagram. birthday.
Demography 77
Assuming that deaths are distributed evenly across the TABLE 5.1. Columns of the life table.
age interval, we can convert the value of 5M20 to 5q20 for
Malagasy women in 1966, to get: Element Definition
n n Mx 5 0:014 x Exact age of the start of the interval

5 q20 ¼ ¼ ð5:5Þ
1 þ n Mx ðn n ax Þ 1 þ 0:014ð5 2:5Þ nax Average number of years lived by individuals
who die in the interval
Thus a force of mortality of 1.4% acting constantly nMx Death rate in the interval [x, x + n)
over a 5-year interval yields a 6.8% probability of death nqx Probability of dying in the interval [x, x + n)
in the interval. lx Cumulative probability of survival to exact
The schedule of nax can be specified in a variety of age x
ways. The most common means of specifying the nax ndx Number of deaths in the interval [x, x + n)
schedule is by using coefficients from a regression of nLx Person-years lived in the interval [x, x + n)
person-years lived on the mortality rate. This is the Tx Person-years of life remaining at exact age x
technique employed by Keyfitz and Flieger (1990) and ex Expectation of remaining life at exact age x
Coale et al. (1983). In general, the only troublesome
parts of nax schedule are in the beginning and the end
of life. For five-year age-classes greater than age five, it
is reasonable to assume that deaths are distributed
randomly across the interval. If this is true then a value 0
of nax ¼ 2.5 is appropriate (as used above). Details can
be found in Keyfitz (1977) and Preston et al. (2001). −1
When mortality is high, people tend to die earlier in the
log(mortality rate)
interval, making the values of nax less than half the
−2
interval width.
Once the interval death probabilities, nqx have been
−3
calculated, the rest of the life table follows in a straight-
forward manner. Denote survivorship by lx. Since the
life table represents an synthetic cohort, the value of l0 is −4
somewhat arbitrary. This first value of the survivorship
column is known as the radix. It is common in the −5
1846
human demographic literature for the radix to be set 1866
to 100 000. Under these circumstances, the lx column is −6
interpreted as the total number of the initial cohort still 0 20 40 60 80 100
living at exact age x. Howell (1979, p. 81, Table 4.1), Age
presents a life table for ever-born children from 165 5.2. The natural logarithm of the central mortality rate for
!Kung women. Using a radix of 100 000, Howell calcu- historical Norway, 1846 and 1866.
lates that l20 ¼ 56 228, meaning that 56.28% of children
ever born survive to their 20th birthday. In biological interval and the average amount of life lived by those
applications, the radix of the life table is usually set to who die is nax . Tx is the number of person-years of
l0 ¼ 1, and lx is interpreted as the probability of surviving remaining life, which is not especially interesting
to exact age x. This is the approach I adopt here. Given a except that it is required to calculate life expectancy,
Ð1
radix of l0 ¼ 1, all other survivorship values follow as: ex ¼ x lðxÞdx. Life expectancy is calculated in the life
a¼xn
Y table as ex ¼ Tx =lx . The elements of the life table are
lx ¼ ð1 n qa Þ; ð5:6Þ summarized in Table 5.1.
a¼0
Survivorship integrates all previous mortality
l0 ¼ 1 by definition since everyone is alive when they experience. Indeed, for a probability distribution for
are born, even if only briefly. age at death F(x), survivorship is equivalent to the com-
The other elements of the life table include plement cumulative distribution of age at death: l(x) ¼
n dx ¼ lx lxþn , which is the fraction of deaths in the 1 F(x). Survivorship is frequently plotted to provide a
interval when the radix is unity and the number of graphical summary of the mortality experience of a
deaths when the radix represents some cohort size, population. However, the logarithm of the central mor-
Ð xþn
and n Lx ¼ x lðxÞdx, which is the number of person- tality rate is a much better plot as it gives far more
years lived in the interval. These person-years include information about the changing nature of age-specific
those lived by both those who live through the interval mortality throughout the life cycle. An example of such
and those who die during the interval. So we can write a plot is given in Figure 5.2, in which I compare the
n Lx ¼ nlx þ n axn dx , since there are ndx deaths in the mortality of Norway in 1846 and 20 years later in 1866.
TABLE 5.2. Life table for Norway (1846). Data from the Human Mortality Database (Wilmoth, 2007).
x nax nMx nqx Lx ndx nLx Tx ex
0 0.26 0.11 0.10 1.00 0.10 0.92 49.82 49.82

1 1.50 0.03 0.10 0.90 0.09 3.36 48.89 54.40
5 2.50 0.01 0.04 0.80 0.03 3.95 45.53 56.58
10 2.50 0.00 0.02 0.78 0.01 3.85 41.58 53.63
15 2.50 0.00 0.02 0.76 0.01 3.78 37.73 49.44
20 2.50 0.01 0.03 0.75 0.02 3.69 33.96 45.37
25 2.50 0.01 0.03 0.73 0.02 3.59 30.26 41.56
30 2.50 0.01 0.04 0.71 0.03 3.47 26.68 37.76
35 2.50 0.01 0.04 0.68 0.03 3.33 23.21 34.13
40 2.50 0.01 0.05 0.65 0.03 3.18 19.88 30.49
45 2.50 0.01 0.05 0.62 0.03 3.03 16.70 26.85
50 2.50 0.01 0.06 0.59 0.04 2.87 13.66 23.08
55 2.50 0.02 0.09 0.55 0.05 2.65 10.80 19.48
60 2.50 0.03 0.13 0.51 0.06 2.37 8.15 16.11
65 2.50 0.04 0.17 0.44 0.08 2.02 5.78 13.09
70 2.50 0.06 0.25 0.37 0.09 1.60 3.76 10.27
75 2.50 0.10 0.40 0.27 0.11 1.10 2.16 7.89
80 2.50 0.12 0.46 0.16 0.08 0.63 1.06 6.47
85 2.50 0.17 0.61 0.09 0.05 0.31 0.43 4.91
90 2.50 0.26 0.79 0.03 0.03 0.10 0.13 3.62
95 2.50 0.34 0.91 0.01 0.01 0.02 0.02 2.89
100 2.50 0.56 1.16 0.00 0.00 0.00 0.00 2.70
Table 5.2 presents a life table for Norway in 1846. demography of the developing world more generally.
The mortality rates are converted to probabilities using a Furthermore, many populations of anthropological
schedule for nax derived from Keyfitz and Flieger (1990). interest are small and the estimation of age-patterns
This approach assumes that nax ¼ 2.5 for all ages above of vital events can be complicated by the very high
5. That is, the average person lives for half the interval in sampling variance. In effect, the demographic signal
which he or she die. This is exactly true if deaths are is frequently swamped by the noise attributable to
uniformly distributed across the interval. However, for chance events acting on small populations. For these
the youngest ages, nax is usually much less than half the and other applications, model life tables have been
interval. If a baby is going to die – particularly in a low- developed to assist with: (1) smoothing mortality data
mortality regime – it is most likely to die shortly after from small samples; and (2) providing full age-specific
birth. Under the Keyfitz system, 1a0 is estimated as mortality schedules when mortality estimates are avail-
a linear function of the mortality rate in the first year, able for only a few ages (or not at all!).
1a0 ¼ 0.07 + 1.71 M0. The coefficients of this model were Model life tables capitalize on the universality of the
derived from the empirical examination of many high- human life cycle. Populations that live in similar
quality mortality data sets. The life table in Table 5.2 ecologies, broadly speaking, respond with similar pat-
was calculated from data on age-specific deaths and terns of mortality. The most commonly used model life
mid-interval populations available on the Human tables were produced by Coale and Demeny, originally
Mortality Database (Wilmoth, 2007) using software that in 1966, with a second edition approximately 20 years
I have developed in the R statistical programming later (Coale et al., 1983). Coale and Demeny present four
language (Jones, 2007; R Development Core Team, “regional” model life table families. All the families are
2008). The software allows users to set different radix derived from historical mortality data, largely of
values and to choose between different nax schedules. European origin. The family determines the overall
shape of the mortality schedule (e.g., the relative contri-
bution of infant or old-age mortality). Within each
Model life tables
family, Coale and Demeny present 25 levels of mortality
For many anthropological applications, vital-event indexed by ex. Level 1 gives e0 ¼ 20, while level 25 gives
registration is nonexistent. This also happens to be e0 ¼ 80. For a more complete discussion of the details
true for much of historical demography and the of the Coale–Demeny model life tables, see Jones (2007).
Demography 79
1.0 help augment incomplete or missing age-specific

Aché mortality data. Future work incorporating demo-
!Kung
graphic shocks into model life tables may help advance
0.8
the utility of this demographic tool. One example of
such an approach is the INDEPTH system of AIDs-
Survivorship
0.6 decremented model life tables for African populations

(INDEPTH Network, 2002). The Coale–Demeny model
0.4 life tables can be generated using software recently
developed and discussed in Jones (2007).
Primatologists have developed model life tables for
0.2 a variety of nonhuman primate species based on the
mortality records of large captive populations (Gage
0.0 and Dyke, 1988; Dyke et al., 1993, 1995).
A useful adjunct to model life tables are the
0 20 40 60 80
Age so-called relational life table methods (Brass, 1971,
1975). Anthropological and historical demographers,
5.3. Survival curves for the !Kung (gray) and Aché (black) super-
imposed on Coale–Demeny West model life table survivorship and those working in areas lacking vital-event registra-
schedules. tion, are frequently faced with the situation where only
the partial mortality schedule for a population is
known. Brass’s basic idea is to take the observed values
For the present discussion, it suffices to say that the and regress them on some known standard. The
“West” model life table family is the most general pat- parameters estimated from this regression allow the
tern and the one most likely to be relevant to anthropo- construction of a full mortality schedule. Ordinary
logical applications. Howell (1979) used Coale–Demeny least-squares (OLS) regression assumes that both
West (CDW) model life tables to smooth the age- dependent and independent variables are normally
structure of the !Kung in order to calculate a life table. distributed, yet mortality probabilities, survivorships,
In contrast, Hill and Hurtado (1996) eschewed the use etc., are bounded on the interval [0,1] and are not
of model life tables in their construction of a life table normally distributed (nor are the errors associated
for the Aché. In Figure 5.3, I plot the survival curves for with them). Brass suggested using a logit transform
the two hunter-gatherer populations along with the on the mortality probabilities. For some variable 0 x
CDW lx schedules for levels 5–15 (e0 ¼ 30 55). 1, the logit transformation of x is
The two curves are very similar, though there is the
^ ¼ logitðxÞ ¼ log x :

hint that the Aché (in which the CDW model life tables Y ð5:6Þ
1 x
were not used in the calculation of lx) may show a
This transforms a variable that ranges over [0, 1] to one
different pattern of early life mortality, a point empha-
sized by Hill and Hurtado (1996) and discussed in that ranges over [ 1, 1]. The original variable x is
Jones (2007). The apparent departure of the Aché mor- recovered through the inverse logit transform,
^ ^
tality schedule from the CDW family raises important x ¼ eY =ð1 þ eY Þ.
questions for the general application of these model Let qx ¼ 1 lx (note the difference between this
life tables. To be included in Coale and Demeny’s col- cumulative qx, which is the probability of dying before
lection of life tables, a population could not be at war exact age x and the life table nqx, the probability of
dying between ages x and x þ n). The Brass relational
or have recently experienced any major demographic
model is thus:
shocks. Given the ubiquity of conflict in human soci-
eties, these conditions for inclusion in the Coale– logitðqx Þ ¼ þ logitðqðSÞ
x Þ: ð5:7Þ
Demeny system suggest that the model life table fam-
ilies may not provide a completely representative The two parameters of the relational model are the
picture of the general human mortality experience. It level a and the shape b. Figure 5.4 plots a CDW six-
is difficult to overstate how commonplace the usage of model survivorship schedule with varying values of a
these model life tables is. As such, it is nearly impos- (Figure 5.4a) and b (Figure 5.4b). In Figure 5.4a, values
sible to know the degree to which more anthropo- of a < 0 are drawn in light gray, while values of a > 0 are
logical populations deviate in biologically significant drawn in dark gray. Values of a < 0 mean that the level
ways from the pattern of the Coale–Demeny model life of cumulative mortality at any given age is lowered;
table families. These observations suggest caution in thus, the survivorship is shifted up. Similarly, values
the uncritical use of Coale–Demeny (or any other) of a > 0 shift the survivorship curve down. As these are
model life tables. However, model life tables nonethe- simply shifts, varying the level of a is shape-preserving.
less remain an important demographic tool that can The effects of varying b are more complex as b controls
(a) (b)
1.0 1.0
0.8 0.8
0.6 0.6
l (x )
l (x )
0.4 0.4
0.2 0.2
0.0 0.0
0 20 40 60 80 0 20 40 60 80
Age Age
5.4. Plots showing the effect of varying a (Figure 5.4a) and b (Figure 5.4b). In both plots, the baseline
lx value is a Coale–Demeny West 6 (thick black line). Figure 5.4a plots survival curves for varying values
of a: curves for ha < 0 in light gray, while curves for a > 0 in dark gray. Figure 5.4b plots survival curves
for varying values of b: curves for 0 < b < 1 in light gray while curves for b > 1.
the shape of the relational mortality schedule. Note period TFRs, as a measure of fertility behavior, can
that b is only defined when it is greater than zero. show substantial distortion. The classical references
Otherwise, there would be negative deaths. When b < 1 for this point are Hajnal (1947), Henry (1953), and
early mortality is accentuated. Survivorship is lower Ryder (1965, 1986). The distortion results from the fact
prior to an inflection point in midlife and is greater that TFR contains two contributing forces. First is the
after this point. When b > 1 mortality in the first half of intensity of reproduction. Populations in which the
life is lower while it is greater following the inflection intensity of reproduction is higher will, all things being
point. equal, have high TFRs. The second contributor to TFR
is timing: when do women begin reproduction, when
do they stop, are there interruptions? Consider a case
FERTILITY where some extreme event (e.g., a war or natural
disaster) caused all women in a particular population
Define the age-specific fertility rate (ASFR) as the to stop reproducing for the duration of the event. If
number of births that occur to women whose last these women ceased reproduction at the same age as
birthday was x, divided by the number of woman-years typical in the population, they would have lower cohort
lived in that age class: TFRs to go with the lower period TFRs measured for a
period overlapping the crisis. However, if these women
Bx
n Fx ¼ ; ð5:8Þ extended their reproductive span beyond the normal
n Lx
period of fertility to make up for the years of lost
where nBx is the total number of births and nLx is the reproduction, they could have the same cohort TFR
woman-years lived between ages x and x þ n. as previous cohorts, but the period TFR calculated for
The total fertility rate (TFR) is the sum of the the period overlapping the crisis will still be lower.
ASFRs from the earliest age of reproduction in the Furthermore, the period TFR for periods subsequent
population to the latest: to the crisis, in which women extend their reproductive
span, will be inflated since women in these periods are
n
X
TFR ¼ n reproducing later in life than they otherwise would.
n Fx : ð5:9Þ
x¼ Thus period TFR can decrease, increase, and decrease
again without a fundamental change in the intensity of
The TFR is the number of offspring a woman would
reproduction.
have if she survived the duration of the reproductive
While TFR is probably the most commonly
span. The TFR is probably the most important measure
employed measure of fertility, it is a very poor measure
of fertility and it is frequently used as an index for the
of population growth because it fails to account for
overall pace of reproduction and development. The TFR
mortality. We define the net reproduction ratio (NRR)
can have either a cohort or a period interpretation,
as the sum of the product of ASFRs and person-years
though the period interpretation is more common. As
lived in the age-class
a period measure, TFR describes the number of chil-
dren a hypothetical woman would bear if she survived n
X
the entirety of her reproductive span and bore children NRR ¼ n Fx n Lx : ð5:10Þ
x¼
at the rates characteristic of the period.
While the period interpretation of TFR is more The NRR is a discrete-time analog to the measure R0
common (because the data are more easily collected), discussed below in the continuous time framework
Demography 81
(see Equation 5.24). If we consider only female births than overall fertility data. Denote the number of
ðMÞ
(and work with a female life table), then in the case of married women in age class x as Kx and the fertility
ðMÞ
NRR ¼ 1, each woman replaces herself with exactly one rate of married women age x as Fx . The total number
daughter and the population will neither grow nor of births can thus be written as:
decline. This is known as replacement level fertility.
X X
B¼ Fx Kx ¼ BM ¼ KxðMÞ FðMÞ
x : ð5:13Þ

The Princeton indices
The index of general fertility, If can now be decomposed
Given the weakness of TFR as a measure of overall
into two components, Ig and Im, known as the index of
fertility, and the fact that the NRR confounds fertility
marital fertility and the index of proportion married
with mortality, there was great interest in developing
respectively. Putting this all together, we have:
alternative measures of the overall fertility of popula-
tions, particularly as a means of measuring the impact Ig Im
zfflfflfflfflfflfflfflfflfflffl}|fflfflfflfflfflfflfflfflfflffl{ zfflfflfflfflfflfflfflffl}|fflfflfflfflfflfflfflffl{
on fertility of the use of contraceptives. A number of P ðMÞ ðMÞ P
F x Kx
ðMÞ
Hx Kx
indices have been developed, but the most widely If ¼ P ðMÞ
P
; ð5:14Þ
Hx Kx Hx Kx
used of these indices are due to Coale (1969). These
are frequently collectively known as the “Princeton bearing in mind that we still only observe B and have
indices.” Ideally, a measure of the overall fertility of a assumed that:
population would use age-standardization common in X
the epidemiology and the demography of contempo- B¼ K ðMÞ FðMÞ
x x : ð5:15Þ
rary state-level societies. The general form of such an
Howell (1979) calculated Coale’s fertility indices for
age-standardized measure would be:
the !Kung hunter-gatherers of Botswana. She showed
P
F x Kx that while the !Kung Im value was as high or higher
I ¼ P ðSÞ ð5:11Þ
than that for a range of other natural-fertility popula-
Fx Kx
tions, their values of Ig and therefore If were surpris-
where a is age at first reproduction, b is the age at last ingly low. Howell attributes this pattern of early and
reproduction, Fx is the ASFR for age x, Kx is the total nearly universal marriage and low marital fertility to
fraction of the (female) population in age class x, and energetics, citing the critical fat hypothesis (Frisch,
ðSÞ
Fx is some standardized value of an ASFR. 1978). More recent research suggests that the critical
However, Coale noted that we frequently lack fat hypothesis is probably incorrect (Ellison, 1981; Elli-
detailed data on the age of mothers, particularly when son et al., 1993). Harpending (1994) suggests that the
dealing with historical data as he was. It was therefore low fertility seen among the !Kung actually reflects the
necessary to develop measures of overall fertility that high frequency of secondary sterility in Southern
used total births rather than births broken down by age African populations (Bushmen included) due to high
class. First, we note that the numerator of this expres- prevalence of bacterial sexually transmitted infections.
P
sion is simply the total number of births, B ¼ Fx Kx . Henry (1961) pioneered the study of natural ferti-
The question then is what fertility schedule with which lity. The term “natural fertility” can cause considerable
to standardize? Coale used the Hutterites, an Anabap- confusion among the uninitiated. A population is con-
tist population living in the upper Midwestern United sidered to be characterized by natural fertility if there
States and Canada that whose fertility was extensively is no parity-specific fertility control. Thus, a popula-
studied (Eaton and Mayer, 1953). The Hutterites rep- tion that contracepted to increase birth-spacing, as
resent one of the highest natural fertility populations long as this was done in a parity-independent manner,
ever studied and therefore make a natural point for is considered to be natural fertility.
ðSÞ
comparison. Letting Hx Fx be the ASFR of Hutterite
women age x, Coale’s standardized index of general
fertility is Model fertility schedules
B
If ¼ P : ð5:12Þ As with mortality, we frequently do not have complete
Hx Kx
fertility schedules for populations of anthropological
There is a long tradition in demography of restricting interest. A number of authors have developed model
attention to marital fertility. In most populations, this fertility schemes, but here I focus on the model of
is a reasonable restriction since the vast majority of Coale and Trussell (1978). Coale and Trussell employ
fertility happens within marriage. The legal framework parametric model fertility schedules derived from
surrounding marriage means that births are more earlier work (Coale and Trussell, 1974). The pattern
likely to be recorded if they happened within a marital of age-specific fertility can be manipulated to achieve
union, making data on marital fertility more reliable a wide range of fertility schedules. The Coale–Trussell
model expresses the realized ASFRs as a function of a that of the most fecund synthetic natural fertility popu-
synthetic natural fertility schedule and two parameters lation. Surprisingly, m ¼ 0.796, indicating that Aché
M and m. These parameters characterize the overall women are far more fecund at later ages than the
level of marital fertility and the degree of departure synthetic natural-fertility schedule would predict. The
from natural fertility respectively. The basis for the remarkable departure of the Aché fertility pattern
schedule is a synthetic natural fertility schedule from the Coale–Trussell–Henry standard is shown in
derived from Henry’s (1961) classic work on natural Figure 5.5. Compare this plot to Figure 5.6b in which
fertility. all the values of the parameter m are positive (which is
The realized age-specific fertility for each age a the expectation based on the interpretation of m as a
between ages 20 and 44 is measure of parity-specific control).
The natural fertility populations in Henry’s sample
ra ¼ na Memva ; ð5:16Þ
all had very high early fertility, in contrast to the Aché.
where va is a set of empirically derived deviations A hypothesis to explain the deviation of the Aché from
presented in Coale and Trussell (1974) and updated in the expected pattern can be derived from life history
Coale and Trussell (1978), and na is the synthetic theory. Assume that early and late fertility trade-off. In
natural fertility schedule derived by Coale and Trussell natural fertility agrarian populations with high energy
from sources in Henry (1961). The age-specific fertili- flux, more rapid growth rates, and therefore earlier
ties for ages 15–19 and 45–49 are interpolated linearly ages of menarche (Ellison, 1981), we might expect high
between zero and the values for age classes 20–24 and
40–44 respectively. M and m are parameters that
Henry
measure the level of overall fertility and the deviation Aché
from the Henry synthetic natural fertility schedule 0.20
respectively.
Dividing both sides of Equation 5.16 by na and
taking logarithms provides a simple means for estimat- 0.15
ASFR
ing the parameters m and M from the Coale–Trussell

model. The equation,
0.10
logðra =na Þ ¼ logðMÞ þ m va ; ð5:17Þ
suggests that we can regress observed age-specific 0.05
(standardized by Henry’s synthetic fertility schedule)
fertilities onto the deviations using OLS to estimate M
and m. An interesting feature of Aché fertility is how
15 20 25 30 35 40 45
fertile women were in their late 30s. We can use the
Age
Coale–Trussell model to demonstrate the extent of the
5.5. Synthetic natural fertility schedule from Henry (1961) and
late-age fertility. A regression of observed Aché ASFRs
used by Coale and Trussell (1978) as the basis for their model
on the Coale–Trussell deviations yields an estimate of fertility schedule along with the fit to the Coale–Trussell model
M ¼ 0.52. This means that the overall level of Aché for the Aché hunter-gatherers of Paraguay (Hill and Hurtado
fertility in the forest period was approximately half 1996).
(a) (b)
0.4
Model ASFR
Model ASFR
0.3 0.15
0.2
0.1 0.05
15 20 25 30 35 40 45 15 20 25 30 35 40 45
Age Age
5.6. Illustration of the effects of varying the two parameters of the Coale–Trussell model fertility
schedules. Figure 5.6a shows the effect of varying the level parameter from M ¼ 1 to M ¼ 0.2.
Figure 5.6b shows the effect of varying the deviation parameter from m ¼ 0.1 to m ¼ 2. Values of
m > 1 cause more severe deviations from the natural fertility shape (i.e., indicate more parity-specific
control).
Demography 83
fertility in the early reproductive years. The trade-off THE EULER–LOTKA CHARACTERISTIC
between early and late fertility means that these women EQUATION
will have lower fertility late in their reproductive careers.
The Aché, who were energy stressed and had relatively Populations renew themselves. A fraction of the babies
late ages at menarche (Bribiescas, 1996; Hill and who are born at some time t grow up to eventually have
Hurtado, 1996), did not have high early fertility and so babies themselves. Our goal is to write an expression
did not suffer the later-life cost in fertility. This hypo- for the number of births at time t, B(t), as a function of
thesis suggests that our understanding of human ferti- the number of births that happened prior to t. The
lity, which derives almost exclusively from populations number of births that occur at time t is composed of
with agriculture, may not well represent the experience two components: (1) births to women already alive at
of hunter-gatherers throughout human history. time t ¼ 0; and (2) births to women born since t ¼ 0.
A more sophisticated means for estimating the ðt
parameters of the Coale–Trussell model by a Poisson BðtÞ ¼ Nða; tÞmðaÞda þ GðtÞ ð5:18Þ
regression with offsets was suggested by Bronström 0
(1985). where, N(a,t) is the number of women age a alive at

A major weakness of the Coale–Trussell model is time t, m(a) is the ASFR of women age a, and G(t) are
that, while m models the departure from natural fertil- births from women alive at t ¼ 0.
ity (i.e., the application of parity-specific control) there Equation 5.18 is the renewal equation. It shows how
is no obvious behavioral implication associated with a the present births were generated by previous births –
particular value of m. that is, how the population renews itself. It is also very
general. We typically want to posit something more
specific in which the number of women alive is itself
Proximate determinants of fertility
a function of schedules of vital events. Invoking a
A great number of ecological, social, behavioral, and number of assumptions, Lotka derived the closed-form
economic factors can contribute to variation in ferti- solution for the renewal equation and explored its
lity. Davis and Blake (1956) noted, and Bongaarts implications in a series of papers in the early twentieth
(1978) formalized the idea that all the myriad potential century (Lotka, 1907; Sharpe and Lotka, 1911; Lotka,
ultimate sources of variation in fertility must pass 1922):
through a small set of proximate determinants of a ð
biosocial nature. These are the so-called proximate 1 ¼ e ra lðaÞmðaÞda; ð5:19Þ

determinants of fertility. Bongaarts (1978) suggests
that there are three general types of proximate fertility where a is age at first reproduction, b is the age at last
determinant: exposure factors, deliberate marital con- reproduction, r is the instantaneous rate of increase,
trol factors, and natural marital control factors. His list and m(a) is the fertility rate of age-a women.
of proximate determinants is provided in Table 5.3. Equation 5.19 is known as the characteristic equa-
The proximate determinants framework has found tion of Euler and Lotka. The unique value of r that
much support in the literature on human reproductive equates the two sides of four is known as the intrinsic
ecology (Wood, 1994). Variations on the Bongaarts rate of increase and it is conceptually identical to the
classification scheme exist, notably that used by Wood r discussed in the above “Exponential growth” section.
and colleagues (e.g., Wood, 1994). There is no analytical solution to Equation 5.19.
Rather, it is typically solved for iteratively. Alterna-
tively, there are approximations. The interested reader
TABLE 5.3. Bongaarts’s proximate determinants of
fertility. is referred to the classic work of Coale (1972) for a
lucid discussion of the characteristic equation.
1. Exposure factors There are a number of assumptions that are used to
(a) Proportion married derive the characteristic equation. For most practical
2. Deliberate marital fertility control factors purposes the most important of these is that the rates
(a) Contraception have been operating in a constant manner for a long
(b) Induced abortion time. In particular, the rates have to be constant for a
3. Natural marital fertility factors period of time that exceeds the age of last reproduction.
(a) Lactational infecundability When this is the so, then the G(t) term in Equation 5.18 is
(b) Frequency of intercourse zero. A population in which this assumption holds is
(c) Sterility said to be “stable.” This terminology unfortunately fre-
(d) Spontaneous intrauterine mortality quently causes confusion. A stable population can grow
(e) Duration of the fertile period or decline. A population in which r ¼ 0 is said to be
“stationary.” Stationary populations clearly do not grow.
(a) (b)
Aché !Kung
75 85
70 80
65 75
60 70
65
55 60
50 55
45 50
40 45
35 40
30 35
25 30
20 25
20
15 15
10 10
5 5
0 0
0.00 0.05 0.10 0.15 0.20 0.00 0.05 0.10 0.15

Fraction Fraction (b)
5.7. Age structure for the stable equivalent populations for the Aché (Figure 5.7a) and !Kung (Figure
5.7b). Dark bars represent the stable age distribution for a stationary population with the same l(x)
schedule as the respective populations.
The characteristic equation relates four fundamen- 1

b ¼ Ð : ð5:21Þ
tal quantities of demography in a single equation. lðxÞe rx dx

Specifically, the characteristic equation ties together
the schedule of age-specific mortality, the schedule of In a stationary population, the proportionate age struc-
age-specific fertility, the age-structure of the popula- ture of the population is given simply by the
tion, and the rate of increase of the population. survivorship. This reflects the well-known relationship
For any given set of l(x) and m(x) schedules, there is between age-structure and standing crop in wildlife
a stable population that would exist if those rates management. Similarly, let life expectancy be the sum
applied for a long period of time. The stable population of the survivorship function:
model that corresponds to a given set of vital rates is ð1
known as the stable equivalent population. e0 ¼ lðxÞdx: ð5:22Þ
Two other equations besides the characteristic 0
equation define the body of theory known as stable

In a stationary population, the following statement is
population theory (Coale, 1972). The first specifies
then clearly true:
the age structure in the stable population:
be0 ¼ 1: ð5:23Þ
rx
cðxÞ ¼ blðxÞe ; ð5:20Þ
That is, the birth rate is simply the reciprocal of the
average life span in the population. When r > 0, each
where c(x) is the number of people in age class x in the
value of l(x) is discounted multiplicatively by a term
stable population and b is the crude birth rate of the
e rx. As r gets very large, this discount factor
population.
approaches 0. This means that as r gets large, b will
We can use Equation 5.20 to compare the stable
also get large. But since the discount term does not
equivalent age structure to the stationary age structure
appear in the expression for life expectancy, the pro-
of two hunter-gatherer populations. Figure 5.7 com-
duct of life expectancy and the gross birth rate will now
pares the two theoretical age structures of the Aché
exceed unity.
(Figure 5.7a) and !Kung (Figure 5.7b). Both popula-
There are a variety of other derived quantities of
tions had positive growth rates and, as a result, both
interest. Define ’ðxÞ ¼ lðxÞmðxÞ, the age-specific net
plots show that the stable-equivalent population is
maternity rate. The sum of the net maternity rate across
younger than the stationary population corresponding
all ages yields the NRR, R0:
to the l(x) schedule.
It is the formula for the crude birth rate that rounds ð ð
out the three primary equations that define the stable R0 ¼ lðxÞmðxÞdx ¼ ’ðxÞdx: ð5:24Þ
model:
Demography 85
The NRR measures the relative size of the population !Kung

from one generation to the next. That is, for a popula- Aché
tion growing at rate r with generation time T, United States
1.5
rT
R0 ¼ e : ð5:25Þ
Reproductive value
While this relationship defines a generation, we typic-
ally want to relate a generation to the birth and death 1.0
rates observed in the population. The generation time
is essentially the average age of childbearing in the
population. However, there is more than one way to
measure the average age of childbearing. One is the 0.5
average age of childbearing in a stable population, AB :
ð
AB ¼ ae ra lðaÞmðaÞda: ð5:26Þ
0.0
The second is the cohort average age of childbearing, 0 10 20 30 40
Ð Age
alðaÞmðaÞda 5.8. Age-specific reproductive value curves for three popula-
¼ Ð : ð5:27Þ
tions: !Kung (Howell 1979), Aché (Hill and Hurtado 1996), and
lðaÞmðaÞda
the United States in 1967 (Keyfitz and Flieger 1990).
In a stationary population, r ¼ 0. Note that Equation
5.24 for R0 and the characteristic equation (Equation
5.19) are identical except for the discount factor e ra. A little algebra yields the form of the reproductive
When r ¼ 0, e ra ¼ 1 for any a. We see that the expression value equation originally presented by Fisher (1958)
for R0 is in fact a special case of the characteristic and that appears in most textbooks:
equation. That is, it is the special case where the sum ð
era 1 rx
of net maternity is exactly unity. In the stationary vðaÞ ¼ e lðxÞmðxÞdx: ð5:29Þ
lðaÞ a
population, each woman will replace herself on average,
with exactly one daughter. For any a > 0, the cohort into which the woman is born
will have declined according the the age-schedule of
mortality. The term outside the integration can thus be
Reproductive value seen as a premium for having survived to age a. The
In a stable population, the expected number of daugh- term inside the integration is the discounted net mater-
ters born to a woman age x is l(x)m(x) and the expected nity at each age x a.
number of offspring born in her lifetime is simply the Reproductive value curves for age-structured popu-
sum of these, R0. However, when the size of a popula- lations have a characteristic shape. Figure 5.8 plots the
tion is changing, offspring produced later in life will age-specific reproductive value for three populations: !
constitute a different proportion of the total population Kung (Howell, 1979), Aché (Hill and Hurtado, 1996),
(i.e., fitness) than offspring born early in life. For con- and the United States in 1967 (Keyfitz and Flieger,
creteness’ sake, say a population is growing at a rate of 1990). Reproductive value at birth (i.e., a ¼ 0) is con-
1% annually. In the 25-year reproductive span of an ventionally set to v(a) ¼ 1. As age increases, so does v(a)
individual woman, the population will have increased until reaching a maximum around the age of first
by over 28% (¼ e0:0125 ). Reproductive value accounts reproduction, a.2 From this point reproductive value
for such changes in the size of the population and the declines, reaching zero at the age of last reproduction,
impacts on individual fitness. ta. In Figure 5.8, both the Aché and the !Kung show the
Reproductive value measures the net present value premium received by women who survive to the first
of offspring produced at a particular age (Fisher, reproductive age class (15). Because mortality is so
1958). The probability of a woman surviving to some high, v(a) increases steeply with age before declining.
age x given that she has already survived to age a is l(x)/ Only 59% of !Kung girls and 64% of Aché girls survived
l(a) and she will have l(x)m(x) offspring. When off-
spring are produced at age x the population has grown
2
by a factor of exa. We assemble these facts into a Age at first reproduction is slightly complicated for Leslie
matrix models with five-year age classes, since the fertility
formulation for reproductive value: values are averaged across adjacent ages for a birth-flow popu-
lation. This means that there is typically nonzero fertility for
ð1 ages before actual reproduction is observed. These are the types
lðxÞ
vðaÞ ¼ erðxaÞ mðxÞdx: ð5:28Þ of modeling compromises that are necessary when trying to
a lðaÞ represent a fundamentally continuous process in discrete time.
to their 15th birthday. In contrast 97.5% of American Matrix A can be represented as a directed graph
girls survived to their 15th birthday in 1967; conse- (Harary, 1969) in which the nodes represent the
quently, their reproductive value rose only nominally age classes and the directed edges represent the transi-
before first reproduction. tions (i.e., the fertilities and survival probabilities).
Figure 5.9 presents the life cycle graph corresponding
to matrix A in Equation 5.30. Survival transitions are
POPULATION PROJECTION: represented by the horizontally aligned edges directed
MATRIX MODELS to the right, while fertility is represented by the left-
directed arcs back to node 1(age class 0–4). In addition
Stable population theory is constructed in continuous to providing an appealing graphical analogue to the
time. However, demographic data typically come in matrix formalism, the life cycle graph provides impor-
discrete age classes. Population projection, it turns tant information about the dynamical properties of the
out, is much simpler to do in a discrete-time frame- system (discussed below).
work than in the continuous time framework of the An initial 10 1 population vector nt can be pro-
stable population model. jected from time t to time t þ 5; we simply premultiply
Consider a population divided into k nonoverlap- n(0) by A:
ping age classes, n years wide. For human populations, ntþ5 ¼ Ant : ð5:31Þ
it is common to divide the reproductive life span into The matrix algebra formalism introduced by Leslie has
9–11 5-year age-classes (quinquennia), depending more to recommend it than simply a compact mechan-
upon the age of last reproduction. Ten is probably the ism for projecting a population. A question that arises
most common number of age classes and that is naturally in the analysis of systems of linear equations
what I will discuss. The ages are thus: 0-4,5-9, is whether there exists a scalar value (i.e., a single
10-14,. . .,45-49. Note that unlike the case of the life number), l, that can substitute for the matrix A in
table, these age classes must all be the same width. projecting the population:
In order to project the population from time t to time
A u ¼ lu; ð5:32Þ
t þ 5, we need 10 equations. For example, to project the
age-class zero individuals to the next age class, we for some vector u. Equation 5.32 generally has a solu-
have n5 ¼ P0n0, where P0 is the probability of surviv- tion. Details of the solution to this equation is beyond
ing from age n ¼ 0 to age n ¼ 5. Each equation that the scope of this chapter.3 When it does, the scalar l is
moves the cohort forward in the life cycle is similarly known as an eigenvalue and the vector u is its corres-
sparse. For the human life cycle divided into quin- ponding eigenvector. In fact, there are k distinct eigen-
quennia and age of last reproduction in the 45–49 values and eigenvectors for the k k matrix A. However,
age class, there are 9 such equations. The last of the when A fulfills two conditions, it is guaranteed that
10 equations accounts for the production of age-class A will have one eigenvalue which is positive, real, and
zero individuals (i.e., reproduction) and takes the form strictly greater than the other k 1 eigenvalues. This is
n0 ¼ F0 n0 þ F5 n5 þ : : : þ Fk nk , where the Fj are the known as the dominant eigenvalue of matrix A and it is
ASFRs (some of which may be zero). the asymptotic rate of increase of the age-structured
Using so many equations to perform a population population. The eigenvector that corresponds to the
projection is cumbersome to say the least. Leslie (1945) dominant eigenvalue is known as the dominant right
noted that matrix algebra can greatly simplify working eigenvector and it corresponds to the stable age distri-
with such systems of linear equations. All the equations bution of the population between ages 0 and k. The
can be compactly represented in a k k matrix, known conditions that guarantee the existence of a single
as a Leslie matrix. The Leslie matrix is square and dominant eigenvalue are known as: (1) irreducibility;
sparse, with the age-specific survival probabilities and (2) primitivity. A non-negative matrix is irreducible
along the subdiagonal, age-specific fertilities along if all of its states can communicate with each other –
the first row and zeros everywhere else. The 10 10 that is, if there is a path from between all the nodes of
Leslie matrix for the human life cycle takes the form: the life cycle graph. Such a graph is said to be strongly
connected (Harary, 1969; Caswell, 2001). An irreducible
0
2
0 F10 F15 F20 F25 F30 F35 F40 F45
3 matrix is primitive if all loops of the life cycle graph
6 P0
6 0 0 0 0 0 0 0 0 0 77 are relatively prime to each other. This ensures that
6 0
6 P5 0 0 0 0 0 0 0 0 77 the growth of the population will be (asymptotically)
6 0 0 P10 0 0 0 0 0 0 0 7
6
6 0 0 0 P15 0 0 0 0 0 0 7
7 aperiodic and that the population eventually converges
A¼6 7: ð5:30Þ
6 0
6 0 0 0 P20 0 0 0 0 0 77 to its stable age distribution.
6 0
6 0 0 0 0 P25 0 0 0 0 77
6 0
6 0 0 0 0 0 P30 0 0 0 77
4 0 0 0 0 0 0 0 P35 0 0 5 3
The interested reader can consult Caswell (2001), or any text-
0 0 0 0 0 0 0 0 P40 0 book in linear algebra.
Demography 87
F10 F15 F20 F25 F30 F35 F40 F45
1 2 3 4 5 6 7 8 9 10
P0 P5 P10 P15 P20 P25 P30 P35 P40
5.9. Life cycle diagram corresponding to the Leslie matrix of Equation 5.30.
Assume that a population is in the stable age distri-

bution. Then let the initial population vector be n0, the
population at some time t is then 0.20
nt ¼ lt n0 : ð5:33Þ
0.15
Using the spectral decomposition of the projection
Sensitivity
matrix, we can say what the population vector will be
at time t starting from any arbitrary initial population 0.10
vector. The spectral decomposition of A, the details of
which are beyond this chapter, uses all k eigenvalues
and eigenvectors and for a deterministic population 0.05
with constant vital rates, will give an exact projection.
See, for example, Caswell (2001) for details.
The stable age distribution is given by the domin- 0.00
ant right eigenvector, u. There also exists a left eigen- 0 10 20 30 40 50
vector for each eigenvalue (matrix multiplication is, in Age
general, not commutative). Denote this eigenvector v 5.10. Fitness sensitivities for Madagascar (1966). Sensitivities
and it corresponds to reproductive values of the ages 0 with respect to survival are in black, and sensitivities with respect
through k. to fertility are in gray.
Fitness sensitivities and elasticities @l

¼ vi uj : ð5:34Þ
@aij
A population with projection matrix A will grow
asymptotically at rate l. This growth rate is the fitness Equation 5.34 assumes that the eigenvectors have been
measure of the age-structured population (Charles- scaled in such a way that <vw> ¼ 1. The element aij in
worth, 1994; Caswell, 2001). Clearly, if we increase the Leslie matrix represents the transition rate from
the values of the survival probabilities and fertilities stage j to stage i.4 The sensitivity of l to a perturbation
in the projection matrix, l will increase. But which in aij is thus the product of the reproductive value of
matrix entries will have the greatest impact on the the receiving age and the stable age fraction of the
growth rate? Knowing the rates to which l is most sending age.
sensitive provides important evolutionary information. Since l is the fitness measure for an age-structured
We want to change the values of A by a small population, the sij measure the force of selection on
amount (i.e., perturb them) and calculate the change in each life cycle transition, aij. Hamilton (1966) used
l that results. Perturbations of the characteristic equa- sensitivities of survival to measure the decline in the
tion were used by Hamilton (1966) in his foundational force of selection with age. Figure 5.10 shows this age-
study of senescence. Caswell (1978) devised a simple related decline in the force of selection. In addition to
formula for the sensitivity of the growth rate l using
the left and right eigenvectors of the projection matrix. 4
Note that the ecologists’ convention of Leslie matrices of the
Let aij be the ij th element of the projection matrix transitions going from column to row is backwards from most
A. The sensitivity of l to a small change in aij is social science applications of transition matrices.
this decline, note that the sensitivities of early survival

start higher than the sensitivities of fertility but that
the sensitivities of fertility decline less steeply with age
0.15
than do the survival sensitivities. This is generally true
for human populations (Jones, 2009). The sensitivities
also appear in the quantitative genetic theory of life
Sensitivity
history evolution in structured populations. Lande’s 0.10
equation for the change in a quantitative character z
uses the sensitivities of l (Lande, 1982). For a popula-
tion with additive genetic covariance matrix G, the
0.05
change in character z for one projection interval is
z ¼ l 1 G s; ð5:35Þ
0.00
where s is a vector of all the sensitivities in the life cycle.
Thus, transitions to which l is highly sensitive will 0 10 20 30 40 50
change more rapidly, provided there is (a) sufficient Age
additive genetic variance, and (b) a covariance structure 5.11. Fitness elasticities for Madagascar (1966). Elasticities with
that allows the trait to change (Lande, 1982). Strongly respect to survival are in black, and elasticities with respect to
negative correlations between traits – particularly traits fertility are in gray.
with high sensitivities – will impede the directional
change of the trait. This is indeed the quantitative
partial derivatives: they measure the local slope of a
genetic basis of the classic trade-offs of life history
perturbation holding every other transition constant.
theory (reviewed in Stearns, 1992).
An actual environmental perturbation rarely changes
Sensitivities measure the force of selection on life
only one transition.
cycle transitions. They are also important for under-
A second interesting feature of elasticities is that
standing the population dynamics of structured popu-
the sum of elasticities of transitions entering a node in
lations in variable environments. See Jones (2005) for
the life cycle graph must equal the elasticities of tran-
discussion in the human evolutionary context.
sitions leaving that node. For age-structured models,
Sensitivities measure the change in the growth rate
this means that elasticity of survival in the reproduct-
l given a perturbation on a linear scale. We can also
ive ages is necessarily less than in the prereproductive
measure the perturbation on a logarithmic scale. Let eij
ages since there are two transitions out of every repro-
denote the elasticity of the growth rate l to a perturba-
ductive age class and only one transition out of each
tion of element aij,
prereproductive age class.
@l aij @ log l
eij ¼ ¼ : ð5:36Þ
aij l @ log aij
CONCLUSIONS
This logarithmic scale measures proportional sensitiv-
ities of l to perturbations. That is, if we perturb vital In this chapter, I have focused primarily on the classic
rate aij by 1%, by what percentage will l increase? For methods of formal demography as they apply to ques-
an elasticity of eij ¼ 0.1, l would increase by 0.1%. tions of human evolutionary biology. Given the
Elasticities have a number of desirable properties. strongly methodological nature of this chapter, I have
First, the sum of all the elasticities in a life cycle is not attempted to provide a comprehensive review of
unity. Elasticities can therefore be seen, albeit in a anthropological or human evolutionary demography.
rather restricted way, as the fraction of total selection The review of anthropological demography by Howell
that a particular life cycle transition experiences. From (1986) still provides pointers to much of the significant
Figure 5.11, we can see that survival to age 5 has an demographic work in anthropology. Hill (1993), Hill
elasticity of 0.184. Thus infant survival accounts for and Kaplan (1999), and Mace (2000) provide reviews
more than 18% of the total selection on the human life of life history theory and its applications to evolution-
cycle, at least for Madagascar in 1966. The fraction of ary anthropology. Since Howell’s (1986) review, there
total selection that prereproductive survival accounts have been a number of laudable studies of the demo-
for in the human life cycle is remarkably constant graphy of small-scale populations, including Hill and
across populations with very different vital rates Hurtado’s (1996) monograph on the Aché, and Early
(Jones, 2009). The degree to which elasticities are and Peters’s (1990) demographic study of Yanomama.
limited as a measure of total selection derives from Outstanding evolutionary demographic work con-
the fact that both sensitivities and elasticities are tinues to be carried out by human behavioral ecologists
Demography 89
working in populations around the world (Pennington TABLE 5.4. Keyfitz (1977) values for the US female
and Harpending, 1991; Borgerhoff Mulder, 1992; Roth, Leslie matrix.
1993; Leslie and Winterhalder, 2002; Sear et al., 2002;
Age Survival Age-specific Population
Sear et al., 2003; Gurven et al., 2007). Roth (2004)
class probability fertility size (106)
presents a novel integration of both evolutionary bio-
logy and culture in anthropological demography. 0 0.99661 0 10.136
The tools of formal demography have a direct bear- 5 0.99834 0.00103 10.006
ing on evolutionary questions. Natural selection is 10 0.99791 0.08779 9.065
fundamentally a demographic process. It results from 15 0.99682 0.34873 8.045
the differential survival and reproduction of heritable 20 0.99605 0.47607 6.546
variants of phenotypes. Humans are long-lived and our 25 0.99472 0.33769 5.614
vital rates change dramatically across the life cycle. 30 0.99229 0.18333 5.632
Such age-structure complicates simplistic arguments 35 0.98866 0.07605 6.193
about selection and makes the use of demographic 40 0.98304 0.01744 6.345
models that incorporate age-structured absolutely 45 – 0.00096 5.796
paramount if we are to understand the process of
selection (Charlesworth, 1994).
While the mathematical formalism of demography
may be unfamiliar to many anthropologists, the calcu- (b) How do you think your projection compares
lation of all the quantities discussed in this chapter is to the actual population structure of the
completely straightforward given appropriate soft- United States in the year 2004?
ware. Matlab is one excellent option. Several popula- (c) What is the growth rate of the population?
tion biology texts have been written that contain What is the stable age distribution? How dif-
extensive example code for many of the calculations ferent is the initial population from the stable
I have discussed in this chapter (Caswell, 2001; Morris population? Show this graphically.
and Doak, 2002). Furthermore, there are a number of (d) Imagine you had the ability to change the vital
very good books on general scientific computing with rates. Which element of the projection matrix,
Matlab (Davis and Sigmon, 2004). Another increas- if perturbed, would increase the growth rate of
ingly attractive alternative is the R statistical program- the population the most? Explain based both on
ming language (R Development Core Team, 2008). R is the mechanics of the calculation and the
a state-of-the-art statistical and numerical program- biology.
ming environment, is available on a variety of comput- 4. Table 5.5 presents life table survivorship (lx) and age-
ing platforms, and is freely available on the Internet specific fertility values for the Hutterites, an anabap-
(http://www.r-project.org). All the calculations and all tist sect living in the Dakotas in the mid 1950s. Plot
the figures except Figure 5.9 that I have produced for the age-specific survival, and net maternity functions.
this chapter were carried out in a recently developed What is the value of R0 for the Hutterites in 1953?
open-source software library for R. This package is What about the total fertility rate (TFR)? What does
freely available and contains a great deal of documen- this tell us about population growth?
tation and worked examples (Jones, 2007). 5. Table 5.6 presents Leslie matrix entries for the
Hutterites. Construct a Leslie matrix (don’t forget
to ensure that it is irreducible). What is the annual
DISCUSSION POINTS rate of increase? What are the elasticities of the
growth rate with respect to perturbations of the
1. Lotka’s characteristic equation connects four projection matrix? What perturbation would have
important demographic phenomena. What are the greatest impact on the rate of increase? Is it
they? feasible for this value to change much? Do you think
2. Why does reproductive value increase until the age that fertility can increase much in this population?
at first reproduction and then decline thereafter? 6. Why do we care about irreducibility and primitivity of
3. Keyfitz (1977) outlines the method of population Leslie matrices? What happens when we repeatedly
projection using Leslie matrices and presents data multiply a matrix that is reducible? What happens
on the female population of the United States in when we repeatedly multiply a matrix that is primi-
1964 to illustrate. His values for the US female tive? Can you think of cases where a demographic
Leslie matrix are reproduced in Table 5.4. projection matrix might be reducible? Primitive?
(a) Construct a 10 10 Leslie matrix for the 7. Total fertility rate (TFR) is probably the most widely
female population of reproductive age using used measure of fertility. However, it is frequently
these data. Project it forward to the year 2004. criticized for not representing the fertility experience
TABLE 5.5. Survival and age-specific fertility

constant. What happens when fertility decreases
values for the Hutterites, 1953. when survivorship is held constant? What are the
demographic circumstances in which each of these
Age lx mx scenarios might apply?
0 1.00 0.00
1 0.96 0.00
5 0.96 0.00 REFERENCES
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6 History, Methods, and General
Applications of Anthropometry
in Human Biology
Noël Cameron and Laura L. Jones
INTRODUCTION is represented by Galen’s (129 – ca. 200 or 216) use of

colloquial Greek words for a limited number of ana-
If it is accepted that a core element of human tomical terms. Galen is thought to have published over
evolutionary biology is about understanding the nature 600 texts but few survived following the destruction
and meaning of morphological variation within and of the library at Alexandria sometime prior to 800 AD.
between the various species of primates that form our Yet his influence lasted for the better part of 1500 years
phylogenetic ancestors, then anthropometry is the until the second stage when Vesalius (1514–1564)
essential tool used in describing morphological vari- worked on a translation of Galen’s Greek works into
ation. Without a standardized form of measurement Latin. Through dissection Vesalius was able to demon-
comparisons between the morphological characteris- strate many of the errors in Galen’s work and his
tics of any two or more individuals is impossible. In the resulting magnus opus, De Humani Corporis Fabrica
acceptance of that simple principle, the complexity of in 1543, is viewed as the foundation document of
anthropometry is glimpsed. For anthropometry to be modern human anatomical description and a good
useful in describing morphology it must involve stand- deal of its terminology. The third stage was expansion
ardized instruments being applied to defined landmarks. of anatomical terminology during the sixteenth and
The instruments must measure in the same units, to the seventeenth centuries through the work of the botanist
same degree of precision, and the ability of the observer and anatomist Caspar Bauhin (1560–1624) in Basel
to repeat the measurement and obtain the same result and in Paris through Franciscus Sylvius (1614–1672)
must be within a range of error that does not signifi- on the brain and vascular system. The fourth stage
cantly alter the outcome of the measurement. is characterized by the many anatomical textbooks
So, modern anthropometry requires a universally published in Latin in the seventeenth century, and in
understood terminology applied to morphological modern languages in the eighteenth and nineteenth
landmarks, universally applied units of measurement centuries although there was no universal agreement
(or at worst units of measurement that have a constant as to terminology, thus anatomical terms for the
relationship), and instrumentation that is appropri- same structure were differently expressed by different
ately designed to measure to a degree of precision that authors. By the late nineteenth century about 50 000
will be useful in describing similarities and differences terms were in use for various body parts. The termino-
in size. In addition, the anthropometrist must be able logy depended in part on the anatomist’s school and
to use anthropometric instruments with an acceptable national tradition. Vernacular translations of Latin and
degree of reliability. It has taken over 350 years since Greek, as well as various eponymous terms, were bar-
a German physician, Johann Sigismund Elsholtz riers to effective international communication. There
(1623–1688), submitted his graduate thesis entitled was thus disagreement and confusion among anato-
“Anthropometria” to the University of Padua in 1654 mists regarding anatomical terminology. The final stage
(Tanner, 1981) for us to be able to be reasonably was initiated between 1887 and 1895 at the Ninth Con-
certain that most of these requirements have been met. gress of the Anatomische Gesellschaft in Basel when
the 50 000 anatomical terms were reduced to 5528
TERMINOLOGY and the resultant Basle Nomina Anatomica became
adopted by a significant number of countries. Some,
Sakai (2007) maintains that the historical development however, maintained their own regional variations and
of anatomical terminology from the ancient to the it was not until 1956, when the first edition of Nomina
modern can be divided into five stages. The initial stage Anatomica was produced by the International
92
History, Methods, and General Applications of Anthropometry in Human Biology 93
Federation of Associations of Anatomists, that some (base 10) and so larger and smaller multiples of each
wider standardization was achieved. Finally, in 1998, unit could be created through the multiplication or
the Terminologia Anatomica became accepted by all division of the unit by the number 10 and its powers.
major anatomy associations as the only international The French Government officially adopted the metric
standard for anatomical terminology. So, at the start of system in 1795 and in 1799 a scientific conference
this millennium, we finally have the ability to involving representatives from Demark, Italy, the Neth-
unequivocally define fixed anatomical landmarks to erlands, Spain, and Switzerland was held to validate the
which measuring instruments can be applied. system and standard prototypes were commissioned.
The original platinum one-meter standard was
made and placed in the Archives de la République in
MEASUREMENT UNITS 1799. However, it was too small, by 0.2 mm, as the
French astronomers Delambre and Méchain, who
The adoption of an internationally agreed system of had spent seven years determining the length of the
measurements seems a self-evident requirement for a arc from Dunkirk through Paris to Barcelona, had
science that espouses internationalism. It is therefore failed to compensate adequately for the earth’s ten-
surprising that anthropology and human biology still dency to flatten out due to its rotation. In 1899, the
discuss their results using two measurement systems; London firm Johnson, Matthey and Co. made a new
Imperial and SI units (SI is the abbreviation of “Sys- prototype meter in the shape of a modified X-shaped
tème International d’Unités”) or foot–pound–second cross-section. It was a bar made of platinum iridium
versus meter–kilogram–second. As of 2007 the United alloy with lines inscribed at each end and the meter
States is partnered with Liberia and Myanmar as the was defined as the distance between the two gradu-
only three countries not to have adopted SI units as ation lines at 0 C. The metric system was officially
their primary system of measurement. The conse- named the “Système International d’Unités” or SI in
quences of this lack of universal conversation was 1960 and the need for more precise way to define a
amply (and expensively) demonstrated on September meter was highlighted. After a number of revisions, the
23, 1999 when NASA’s $125 million Mars Climate most recent definition of a meter, based on an unchan-
Orbiter was lost on entry to the Mars atmosphere ging value, came in 1983. The General Conference on
10 months and 416 million miles after launch because Weights and Measures defined a meter as “the length
the Lockheed constructors of the spacecraft used of the path travelled by light in a vacuum during a time
Imperial units of the Poundal and the Jet Propulsion interval of 1/299 792 458 of a second” and this remains
Laboratory controlling the craft used SI units of the definition today.
Newtons (1 Newton ¼ 7.23 Poundals). No such expense While the actual length of the meter has changed
is likely to occur in anthropology by the application of very little since it was established, the precision by
two measuring systems, but clearly standardization is which it is measured has been noticeably enhanced.
an absolutely fundamental requirement for anthropo- This point is perhaps the most important for contem-
metric measurement. Standardization of measurement porary anthropometry. Anthropometry is used in a
became a cause of concern during the enlightenment range of scientific disciplines including medicine,
in eighteenth-century France in which the Ancien evolutionary biology, anthropology, human biology,
Régime employed 250 000 units of measurement (Alder, ergonomics, sports science, and forensic medicine
2002) that differed mainly depending on whether one to name but a few. The extent to which differences
was buying or selling the commodity to be measured; between values are deemed to be significant, either
clearly a short foot of cloth was advantageous to the statistically or, more importantly, biologically depends
weaver and disadvantageous to the tailor. on the precision with which we measure. Differences of
The desire for “Liberté, égalité et fraternité” that led 200 g in the weight of adult humans are of little import-
to the French Revolution at the end of the eighteenth ance but such differences in weight between babies at
century, and with it the change of mindset from dogma- birth are associated with a range of constraints upon
tism and imperial decree to evidence-based knowledge, intrauterine growth such as maternal smoking and mal-
was the perfect historical moment to espouse a universal nutrition. Thus precision becomes an appropriate cause
system of measurement. In 1791, the French Academy of for concern in anthropometry.
Sciences suggested that a meter should be defined as one
ten-millionth of the earth’s meridian along a quadrant
(i.e., one ten-millionth of the distance between the equa- INSTRUMENTS AND TECHNIQUES
tor and the North Pole). The meridian system was both
simple and scientific as the unit of length (meter) could The development of anthropometric instrumentation,
be used as the basis for measures of both mass and unlike the turbulent history of the acceptance of ana-
volume. In addition, the metric system was decimal tomical terminology and measurement units, is
94 Noël Cameron and Laura L. Jones
marked by the agreement with which instrument to have used a measuring board known as a “mecometre”
design is characterized. The fact that an instrument developed by a French physiologist, François Chaussier,
to measure length must necessarily incorporate a rigid and described by Murat (1816; cited by Tanner, 1981)
rod and two projecting arms, one fixed and the other as consisting of a square wooden rod, marked in deci-
moveable, appears to have been accepted from the meters, centimetres, and millimeters. There were two
very first anthropometric instruments of which we ends made of copper, one fixed, and the other movable.
have descriptions. Johann Sigismund Elsholtz’s thesis As Quetelet had used such a purpose-built instrument
in 1654 on “Anthropometria” contains an illustration to measure neonates it seems reasonable that he also
of what must have been one of the first “anthrop- used purpose-built apparatus to measure his children.
ometers.” This instrument has a transverse rod (the At about the same time in England, Galton (1874) was
regula) moving up and down a vertical rod, which commenting to the Anthropological Institute on the
Elsholtz describes as “similar to the draughtsman’s report by Fergus and Rodwell (1874) of the growth of
rule except that at one end it has a special wider Marlborough College schoolboys. Fergus and Rodwell
portion composed of two projecting angular pieces had measured the height, weight, chest, upper-arm,
made so that when held against any object having a and head circumferences of 550 boys aged 10–19 years.
regular section it will be kept in a straight line . . .” Although the data were cross-sectional, it is of interest
(Tanner, 1981, p. 45). that they used a stadiometer, described by them as a
Whilst the development of instrumentation took “vertical board provided with a sliding square at right
place across a broad series of scientific disciplines angles to it.” Galton described it more fully in a foot-
aimed at measuring the human body it was in the note to his comments as: “A bracket sliding between
field of Auxology – the study of human growth – that vertical guides, and balanced by a counter-weight,
development of appropriate instrumentation was of acting over two pulleys (which would) be found easy,
singular importance. This is because the measurement quick and sure in its action. The vertical board and
of human growth deals with a constantly changing foot-piece may be dispensed with, if the guides can be
object. Whilst we now appreciate that children grow nailed to the wall” (Galton, 1874, p. 126). The develop-
according to an aperiodic series of saltatory bursts ment of such technology for measuring height means
punctuating periods of stasis (Lampl et al., 1992), the that researchers were well aware of the difficulty
majority of our knowledge of the process of growth is of obtaining accurate measurements and were not
based on measurements taken too infrequently to be prepared simply to use the anthropological instrumen-
able to record that pattern. When measured on a tation which existed to measure skeletal remains.
monthly or, more commonly, three-monthly basis the Anthropologists were also well aware that the
pattern of human growth appears as a smooth curve. standardization of anthropometric techniques and
The first longitudinal study of human growth, and procedures was a necessity. Until 1870 the Broca tech-
with it the demonstration that accurate and repeatable niques of anthropometry were universal. Growing
measurement techniques were being used, is usually individualism and the isolationism of Germany
credited to Count Philibert Guéneau de Montbeillard, resulted in three conferences dealing with German
whose study on the growth of his son was published in anthropological anthropometry during the nineteenth
a supplement to Buffon’s Histoire naturelle (Tanner, century: the Congress of the German Anthropological
1962). Between 1759 and 1777 he measured his son Society in 1874, the Craniometric Conference in
at six-monthly intervals. Scammon (1927) translated Munich in 1877, and the Berlin Conference in 1880.
these raw data into a height distance graph and D’Arcy The result of these conferences was the “Frankfurt
Thompson (1942) derived a velocity graph which dem- Agreement” adopted at the 13th General Congress of
onstrate by their smooth nature that de Montbeillard the German Anthropological Society held at Frankfurt-
must have used a standard measurement technique on-Main. Thus the French and German schools of
and appropriate instrumentation. To illustrate the con- anthropometry were established. Further attempts at
stancy of technique and instrumentation over the last the unification of anthropological anthropometry
two and a half centuries, Tanner (1981) records two occurred during the 1890s in Paris under the individual
examples. The first records the growth of children from initiative of R. Collignon (1892) and at the 12th Inter-
the Carlschule in Stuttgart between 1772 and 1794 national Congress of Prehistoric Anthropology and
(see Hartmann, 1970 in Tanner, 1981) and the second, Archaeology of 1892 in Moscow. Hrdlička (1947) thought
in the nineteenth century, Quetelet’s (1870) measure- that neither of these attempts accomplished anything
ments on his own son and daughter from age 5 to substantial, but standardizations became at least a
maturity as well as on the two daughters of a friend, recognized necessity. An International Agreement for
one between the ages of 10 and 17 and the other the Unification of Anthropometric Measurements to be
between the ages of 12 and 17. Quetelet in particular made on the “Living Subject” was drawn up in Geneva
was known from his cross-sectional studies of neonates at the International Congress of 1912. Although this
agreement did not deal with children it gave general when they did not precisely meet the needs of the
principles of measurement and detailed definitions of auxological situation. An anthropometer may, for
49 measurements. instance, have been fixed to a board to facilitate
The anthropometry peculiar to somatic growth the measurement of recumbent length. In addition,
that we use today had its recent development in the American studies promoted the development of instru-
American longitudinal studies of the first half of mentation such as skinfold calipers. They did much
this century. From 1904 to 1948, 17 such studies were to influence more recent researchers in the field of
started and 11 completed. Their complexity varied growth and development on both sides of the Atlantic.
from the relatively simple elucidation of the develop- In Britain few longitudinal growth studies were
ment of height and weight to data yielding correlations undertaken before 1949. Fleming’s study of stature
between behavior, personality, social background, and and head measurements (Fleming, 1933) was the only
physical development. One factor common to all was one to be published for use as standards of reference by
the desire to maintain accuracy of measurement. 1950 (Tanner, 1952), although other longitudinal stud-
Administrative problems and staff changes meant ies had been undertaken which would later produce
that this was not always possible but runs of 10 years worthwhile results. Alexander Low had measured 900
with the same measurement team are to be found newborn babies between 1923 and 1927 and followed
in the Berkeley Growth Study of 1927 (Bayley, 1940), 65 of the boys and 59 of the girls with annual measure-
and the Yale Study of the same year (Gesell and ments until the age of five years (Low, 1952). These
Thompson, 1938). data were later to provide Tanner and his colleagues
Research workers were aware of the need for with the opportunity to revisit some of these subjects
comparability of measurements and published precise as adults and repeat the measurements and so investi-
accounts of their methods and techniques, with suit- gate the relationship between growth in the preschool
able adaptations for the measurement of growth. The years and eventual adult size (Tanner et al., 1956).
three most important and informative accounts from At the Institute of Social Medicine in Oxford Professor
this period are those of Frank Shuttleworth (1937) for John Ryle set up the Oxford Child Health Survey in
the Harvard Growth Study of 1922 (made in the School 1944. This was originally designed to investigate illness
of Education), Harold Stuart (1939) for the Centre for experience in the first five years of life and the effect
Research in Child Health and Development Study of on growth. In the end it provided considerable data
1930, and Katherine Simmons in her reports of the to allow the original development of bone-specific-
Brush Foundation’s Studies of 1931 (Simmons, 1944). scoring systems for skeletal maturity assessments
Stuart (1939) provides the most complete account of (Acheson, 1966) and longitudinal data up to the age
measurements used for auxology using the techniques of 18 years.
that resulted from the International Congress of 1912, The Harpenden Longitudinal Growth Study set up
“with diversions from these techniques at appropriate by J. M. Tanner and R. H. Whitehouse in 1949, became
times.” H. V. Meredith (1936) is unique in his percep- the strongest influence in British studies of human
tion of the problems involved in the measurement growth, and did much to advance auxological anthro-
of human growth at the time of the early US studies. pometry. Whitehouse measured all the subjects from
The multitude of papers he published on the growth the beginning of the study and was to stay with the
of children from Iowa City (Iowa), Massachusetts, study for its duration into the 1970s. He created a
Alabama, Toronto (Canada), and Minnesota contain virtual record in taking every measurement on every
excellent examples of reliability control. He was con- child on every occasion for 25 years. The team of
vinced that long-term studies of physical growth would Tanner and Whitehouse radically altered the approach
only be valid if preliminary detailed investigations to auxological anthropometry. Whitehouse was dis-
were made into the accuracy with which body dimen- satisfied with the instrumentation available and
sions could be measured during growth. If the growth developed the Harpenden range of instruments that
increment from one age to the next was less than the are recognized today as being among the best in the
90th centile of the differences between repeated meas- world. They are accepted internationally for their
urements of a chosen dimension, he thought it unwise accuracy, consistency, and ease of use. Their principal
to take the measurement. Detailed descriptions of the advance was to eliminate graduated rules for measuring
measurements his team used are included in his linear distances and instead to use counter mechan-
reports. He and his colleague Virginia Knott (1941) isms. These counters were turned by a simple ratchet
criticized the sparsity of modern techniques and system and displayed the measurement in millimeters.
the lack of information pertaining to their reliability. Reading errors were thus minimized.
These American studies almost exclusively used The International Children’s Centre Coordinated
accepted anthropological instrumentation such as Longitudinal Growth Studies had a major effect on
Martin anthropometers, which would be modified standardizing anthropometric measurements and
growth study design. Growth studies were set up in what the actual true height is. We can improve the
France, Sweden, Britain, Switzerland, Belgium, Dakar accuracy (and decrease error) by ensuring that we use
(Senegal), Uganda, and Louisville (Kentucky), and an appropriate, specific, purpose-made, valid, cali-
coordinated by meetings of the growth study teams brated instrument to measure the child and by using
every two years. Initially these teams discussed their a properly trained observer. Accuracy may be deter-
methods and eventually their results. The papers and mined from a test–retest experiment in which the
articles that resulted directly or indirectly from these standard error of measurement (Smeas) or technical
studies form a bibliography of 948 references (Inter- error of measurement (TEM) is calculated (Cameron,
national Children’s Centre, 1977). The International 1978, 1983, 1984; Lohman et al., 1988). Precision is
Biological Programme (IBP) that brought together either the proximity with which an instrument can
scientists from all over the world under the umbrella measure a particular dimension or the smallest unit
of research in “Human Biology” during the years 1962– of measurement chosen by the observer. Note that this
1972 gave rise to one of the standard texts for research is different from accuracy in that it relates to the
into the human biological sciences. Weiner and Lourie’s smallest unit of measurement possible (or chosen)
(1969) IBP Handbook, now revised and in its second with a particular instrument. So a stadiometer that
edition (Weiner and Lourie, 1981), forms the source for measures height to the nearest centimeter is not
many scientists who wish to use standard techniques. as precise as one that measures to the nearest
Its value is in its acceptance, by many, as the source, millimeter. Clearly accuracy and precision are related
not only for techniques of measurement but also for in that reliability can only be measured within the
many other techniques that are applied in research limits imposed by the precision of the instrument or
on human adaptability. Weiner and Lourie were not observer. Thus two observers may appear to have equal
attempting to illustrate new concepts of technique but reliability when they use a stadiometer to measure
rather to illustrate the most appropriate techniques height to the last completed centimeter but a more
available which would allow the greatest degree of precise instrument, that measures in millimetres,
comparability. In parallel to the work of the IBP, a might demonstrate that one of the observer is more
conference, chaired by Hetzberg, was held in 1967 on accurate than the other. Reliability is the extent to
the standardization of anthropometric techniques and which an observer or instrument consistently and
terminology. This meeting was attended by anthro- accurately measures whatever is being measured on a
pologists, engineers, dental and medical researchers, particular subject. Note that reliability involves three
physical educationists, and statisticians and helped to sources of error; the observer, the instrument, and the
improve the comparability of data across different subject. Also, reliability involves two characteristics;
fields by providing a range of standardized anthropo- consistency and accuracy. Reliability can also be
metric techniques and terminology (Hertzberg, 1968). assessed in a test-retest experimental design in order
Noël Cameron’s The Measurement of Human to calculate the standard deviation of differences (SD)
Growth in 1984 (Cameron, 1984) and Tim Lohman’s (Cameron, 1978, 1983, 1984). Finally, validity is the
Anthropometric Standardization Reference Manual extent to which a measurement procedure measures
(Lohman et al., 1988) have now become the standard or assesses the variable of interest. For instance, the
reference texts for anthropometry. The former was the measurement of total body fat may be measured by
result of Cameron’s liaison with Tanner and White- dual energy X-ray absorptiometry (DXA) or by densi-
house in London and the latter resulted from a tometry. The former is more direct than the latter and
National Institutes of Health (NIH) conference held is thus more valid. Similarly, growth is stature is most
to help standardize anthropometric measurements validly assessed by measuring height rather than by
in 1988. measuring leg length. These concepts are discussed
in detail in Cameron (1978, 1983, 1984). Within the
measurement of human growth it is important to know
RELIABILITY one’s accuracy and reliability both for the absolute
(cross-sectional) determination of a child’s height and
It is important to define the terms accuracy, precision, for the (longitudinal) determination of growth velocity.
reliability, and validity because an understanding of Obviously when taking two measurements of height to
these concepts is fundamental to obtaining anthropo- calculate growth velocity the estimation is affected by
metric measurements. According to the Oxford English two sources of error, one for each height estimation.
Dictionary accuracy is described as “. . . careful, pre- The interval between measurement occasions will be
cise, in exact conformity with truth.” In most measure- determined, to some extent by the reliability of the
ment situations we do not know what “truth” is. For observer. If, for instance, the observer has a reliability,
example, when we measure a child’s height we only or SD, of 0.3 cm and the child is growing at a rate
have the estimation of that height, we do not know of 4 cm/year then growth will not be certain to have
occurred (with 95% confidence limits) until the differ- cleaning. Sample size (N) for each variable identifies
ence in heights between two measurement occasions is missing data – a complete dataset should have the
greater than 1.96 0.3 cm, or 0.59 cm. It will take this same N for each variable unless the research design
child 54 days to grow 0.6 cm and thus measurements excludes certain cases. Measures of central tendency
taken on a monthly or even two-monthly basis will be including the mean, median, and mode provide clues
subject to observer error. The minimal time between as to the Gaussian (normal) nature of the distribution
measurement occasions for this child should be at least and the potential significance of departures from nor-
three months to ensure that false growth due to obser- mality. The means three moments (SD, variance, and
ver error is minimal. skewness) provide information on variability and
Generally linear dimensions, e.g., height, are more importantly whether the shape of the distribution
accurate than those involving soft tissue, e.g., skin- departs significantly from normal. The range provides
folds. Linear dimensions are most often taken between the largest and smallest values of a variable and thus is
bony landmarks with little or no compressible tissues an immediate check on whether all values fall within
to interfere with accurate measurement. Soft tissue the expected limits. This is particularly important
measurements, such as arm circumference, involve for the recognition of erroneous values in categorical
compressible subcutaneous fat and muscle that will variables that have predetermined upper and lower
reduce accuracy and reliability. It is thus of some bounds.
importance for the observer to be aware of exactly
what is being measured within a particular dimension. 1. Identification of missing data. Having identified
For instance an observer measuring triceps skinfold the absence of data through the sample size for
without an understanding of the anatomical relation- each variable, each missing value in the database
ship between subcutaneous fat and muscle is unlikely should be cross checked with the original hard
to appreciate the importance of the need to separate copy to ensure that missing data are actually miss-
the subcutaneous fat layer from the muscle layer ing rather than missed in the capturing process.
during measurement. Similarly, an observer ignorant Nonmissing data should be captured. Prior to con-
of skeletal anatomy will not appreciate the need siderations regarding the type of analysis to be
for straightening the vertebral column or of applying undertaken it is not necessary to make decisions
pressure to the mastoids prior to the measurement regarding the imputation of missing values. The
of stature. purpose of editing is to present a clean (error-free)
database for statistical analysis.
2. Identification of potentially erroneous data through
DATA EDITING the detection of outliers (known as flagging). Out-
liers will be values that are at the extremes of the
Once anthropometric data have been collected there is expected distribution. Within categorical variables
a need to ensure that these data are free from errors. these will commonly be outside the predetermined
Data editing involves the processes required to convert range. Outliers within continuous variables, how-
recorded data into an analysis dataset. This process ever, present a different paradigm in that they may
involves cleaning the captured dataset (“capturing” in actually be extremes of normal and not erroneous.
this context refers to the process of inputting data from Outliers may be illustrated through frequency dis-
the raw paper files into a computerized database) to tributions, standard deviation checks, and bivari-
identify and deal with missing and erroneous data. ate scatter plots.
It involves a number of systematic stages that need to a. Frequency distributions are used with discrete
be completed before analysis is initiated. The stages of categorical variables to highlight cases that fall
cleaning are dependent on whether the data have been outside the expected range.
collected in a cross-sectional (XS) or longitudinal b. Ninety-five percent of the normal (Gaussian)
research design but initially the stages are the same distribution is within 2 SD, thus values of
for both types of data. continuous variables that lie outside this range
may be either erroneous or extremes of normal.
This “standard deviation check” can be employed
STAGES OF DATA CLEANING for all continuous variables but the extent of
the range (e.g., 2, 3, or 4 SD) will depend on
The first action on the captured database is to generate the importance of correctly identifying true
descriptive statistics including the sample size, meas- extremes. Where doubt exists as to the authenti-
ures of central tendency, SD, variance, skewness, and city of an outlier then when possible “witness
range. Each of these statistics provides a specific piece variables” should be employed to help make
of information that guides the process of editing and cleaning decisions. For example if a participant’s
weight lies outside of 2 SD, then one can one should study each case individually and
examine skinfold or girth data (if these were decide with reference to the context of the
collected) to determine if it is plausible that the study, and the change in witness variables, if a
child is either over or underweight. case may have lost weight or if the case needs
c. Bivariate scatter plots provide a pictorial repre- to be excluded from further analysis.
sentation of the relationship between two vari- 5. Once stages 1 to 3 have been completed on a cross-
ables, e.g., height and weight, and thus also the sectional basis and stage 4 has been completed on a
presence of outliers who do not conform to the longitudinal basis, stage 3 (5% random sample
expected distribution of the scatter. checks) should be repeated using the complete lon-
Although it should only be done with gitudinal dataset. If no 5% random sample errors
extreme caution, erroneous data points can are found then the longitudinal data can be used
either be excluded from analysis or the analysis for analysis.
should be executed both with and without the
A comprehensive record of every cleaning change and
erroneous data points and significance of the
the reason why changes were made should be main-
difference between both outcomes reviewed in
tained (such as in the form of a data cleaning report) so
the light of the hypothesis being tested.
that each correction can be subsequently traced. Once
3. The third stage involves checking the captured data
cleaning has been completed and comprehensively
of a 5% random sample with the raw data file. This
documented, one may then begin to derive variables
is because not all errors result in extreme outliers
from the cleaned data such as body mass index (BMI)
but some may be contained within the normal dis-
and standardized scores.
tribution of the data. A 1% error limit should be
imposed, meaning that if there are errors in more
than 1% of the selected cases then a further 5% TECHNIQUES IN ANTHROPOMETRIC
random should be selected and the process MEASUREMENT
repeated. This process should be repeated to a
maximum of three iterations. If greater than 1% The organization of this chapter is such that a meas-
of these data are found to be erroneous in each urement technique is described with the instrumenta-
of the random sample checks then a repeat of tion recommended for the most accurate and reliable
cleaning stages 1 to 3 should be undertaken. results. The measurements chosen for description are
those that are the most relevant for human and evolu-
If stage 3 is completed successfully then cleaning is
tionary biologists; linear dimensions of hard and soft
complete for XS data and analysis may begin. If longi-
tissue and in particular lengths, diameters, circumfer-
tudinal data have been collected then stages 4–5 should
ences, and skinfolds. The following measurements will
be employed.
be described: weight; linear dimensions (e.g., stature
4. Flagging variables need to be created between and supine length); circumference/girths (e.g., waist
longitudinal data collection points. and hip); skinfolds (e.g., triceps and subscapular).
a. Longitudinal research designs investigate the A detailed glossary of anatomical surface landmarks
biology of change and commonly have an can be found towards the end of this chapter.
expected directionality, either positive or nega-
tive. For example if the height of a child was
MEASURING PROCEDURES
measured at 9 and 10 years of age, height is
expected to increase or show positive change.
The accuracy with which the following measurements
Flag variables where the value at the first time
may be obtained can be maintained at a high level by
point is subtracted from the value at the second
following a few simple rules of procedure:
time point should be created and the expected
direction of change should be checked for all of 1. Ensure that the subject is in the minimum of
the derived values. clothing or at least in clothing that in no way inter-
b. If a case has, for example, shown an inappropri- feres with the identification of surface landmarks.
ate direction of change then the raw hard data 2. Familiarize the subject with the instrumentation,
files at each time point should be cross-checked which may appear frightening to the very young
prior to a decision regarding exclusion. subject, and ensure that he or she is relaxed and
c. With nonlinear dimensions such as weight, lon- happy. If necessary involve the parents to help in
gitudinal cleaning can be more difficult as it is this procedure by conversing with the child.
feasible that a case particularly in constrained 3. Organize the laboratory so that the minimum of
environments may have lost weight between movement is necessary and so that the ambient
time points. Where flags are raised with weight, temperature is comfortable and the room well lit.
4. Place the recorder in such a position that he or Assuming that the scales are regularly calibrated, the
she can clearly hear the measurements and is observer ensures that the subject is either dressed in
seated comfortably at a desk with enough room the minimum of clothing or a garment of known
to hold recording forms, charts, and so on. weight that is supplied by the observer. The subject
5. Measure the left-hand side of the body unless the stands straight, but not rigid or in a “military position,”
particular research project dictates that the right- and is instructed to “stand still.” If the instrument is a
hand side should be used or unless the compara- beam balance then the observer moves the greater of
tive projects have used the right-hand side. the two counter-weights until the nearest 10-kg point
6. Mark the surface landmarks with a water soluble below the subject’s weight is determined. The smaller
felt-tip pen prior to starting measurements. counter-weight is then moved down the scale until the
7. Apply the instruments gently but firmly. The subject nearest 100 g mark below the point of over balance is
will tend to pull away from the tentative approach reached and this is recorded as the true weight. This
but will respond well to a confident approach. procedure is necessary to determine weight to the last
8. Call out the results in whole numbers; for example, completed unit. If the weight is taken as the nearest
a height of 112.1 cm should be called out as “one, 100 g above true weight then that 100 g is greater than
one, two, one,” not as “one hundred and twelve actual weight and the last unit has not been completed.
point one,” nor as “eleven, twenty-one.” Inclusion Determining the weight of neonates can be a noisy and
of the decimal point may lead to recording errors tearful procedure but need not be if the help of the
and combinations of numbers may sound similar; mother is solicited. The observer simply weighs mother
for example, “eleven” may sound similar to “seven.” and child together and then transfers the baby to his or
9. If possible, measure the subject twice for all dimen- her assistant’s arms and weighs the mother by herself.
sions but particularly for skinfolds. The recorder The baby’s weight can thus be determined by differ-
should check that the retest value is within the ence, (weight of mother þ baby) (weight of mother),
known reliability of the observer. If it is not then a and the child is left relatively undisturbed.
third measurement is indicated. For a final value
average the two that fall within the limits.
10. Do not try to measure too many subjects in any WEIGHING SCALES
one session. Fatigue will detract from accurate
measurement for which concentration is vital. The measurement of weight should be one of the easi-
11. Greater co-operation from the subject will result est of anthropometric measurements and yet results
if the appearance of confidence and efficiency is are often inadequate due to inappropriate instrumen-
given by being clean and smartly dressed. tation. Precision to 0.1 kg (100 g) is acceptable as long
as regular calibration ensures the minimum chance of
error and appropriate steps are taken to tare for any
TRAINING clothing the subjects are required to wear. The mech-
anical instrument best suited to repeatedly accurate
The training of anthropometrists is extremely import- weight measurements is that designed on the balance-
ant and should be planned carefully. Practical instruc- arm principle with two balance arms. One major bal-
tion from a trained anthropometrist may take only a ance arm measures to greater than 110 kg in steps
matter of days but the new observer will need to prac- of 10 kg and the other, minor arm, to 10 kg in steps of
tice his or her techniques over a number of weeks to 100 g. Such an instrument is capable of measuring
acquire the required accuracy. It is a good idea for the individuals from birth through to adulthood with
learner to pursue regular reliability checks on his or appropriate modification to include a baby-pan and
her accuracy and to refer back to the expert for checks seat for subjects unable to stand and/or too large for
on technique. As with all practical techniques, the the baby-pan. Electronic balances are also available at
objective view is usually more critical and therefore less than the cost of mechanical machines and appear
more helpful. Familiarity with the instruments is vital well suited to growth clinic use as long as their power
to the precise collection of anthropometric data. The source (usually batteries) is regularly checked.
observer should be able to service and calibrate the
instruments to the required degree of precision.
STATURE (FIGURE 6.1)
WEIGHT The subject presents for the measurement of stature

dressed in the minimum of clothing, preferably just
The measurement of weight should be the simplest and underclothes, but if social custom or environmental
most accurate of the anthropometric measurements. conditions do not permit this then at the very least
It is advisable to place a weight, of about 0.5 kg, on

the headboard. This weight presses down on the hair
thus flattening any hairstyle and overcomes the natural
friction of the machine so that any upward or down-
ward movement during the measurement is recorded
on the counter. With the subject in the correct position
he or she is instructed: “Take a deep breath and stand
tall.” This is done to straighten out any kyphosis or
lordosis and produce the greatest unaided height. It is
at this point that the observer applies pressure to the
mastoid processes – not to physically raise the head but
to hold it in the position that the subject has lifted
it to by breathing deeply. The subject is then instructed
to “Relax” or to “Let the air out” and “Drop the shoul-
ders.” The shoulders are naturally raised when the
subject takes a deep breath and thus tension is
increased in the spinal muscles and prevents total
elongation of the spine. Relaxing or breathing out
releases this tension and commonly produces an
increase of about 0.5 cm in absolute height. The effect
of this pressure or traction technique is to counteract
the effect of diurnal variation that works to reduce
6.1. The measurement of stature.
stature during the normal course of a day. This reduc-
tion may be as much as 20 mm (Strickland and
without shoes and socks. The wearing of socks will not, Shearin, 1972) but the pressure technique reduces that
of course, greatly affect height, but socks may conceal to less than 4.6 mm over the whole day (Whitehouse
a slight raising of the heels that the observer from his et al., 1974). Stature is read to the last completed unit
or her upright position may not notice. The subject is whether from a counter or graduated scale. Height is
instructed to stand upright against the stadiometer not rounded up to the nearest unit as this will produce
such that his or her heels, buttocks, and scapulae are statistical bias and almost certainly invalidate esti-
in contact with the backboard, and the heels are mates of height velocity.
together. As positioning is of the greatest importance
the observer should always check that the subject is in
the correct position by starting with the feet and STADIOMETERS
checking each point of contact with the backboard as
he or she moves up the body. Having got to the shoul- The stadiometer is composed of a horizontal head-
ders he or she then checks that they are relaxed, by board and vertical backboard. The backboard must
running his or her hands over them and feeling the be so designed that it maintains a vertical position
relaxed trapezius muscle. The observer then checks whether free-standing or wall-mounted and the head-
that the arms are relaxed and hanging loosely at the board must always move freely over the surface of
sides. The head should be positioned in the “Frankfurt the backboard. The method of recording the measure-
plane,” and the headboard of the instrument then ment must be accurate and reliable and, if necessary,
moved down to make contact with the vertex of the capable of easy calibration. Usually a counter mechan-
skull. To ensure that the Frankfurt plane has been ism or graduated rule is used for this purpose. It has
achieved the observer may find it helpful to use either been found that counter mechanisms lead to fewer
of the following techniques. The observer bends down reading errors but, in an uncontrolled environment,
so that his or her eyes are level with the plane and notes they may be broken by abuse. Reading from graduated
that the lower orbits of the eyes and the external audi- rules requires the observer to be at the same height as
tory meatii are in a horizontal line. Alternatively, when the cursor to avoid parallax errors. It is very important
using instruments with a counter, he or she may grip to appreciate that in the absence of a purpose-built
the head with open hands and pivot it backwards stadiometer of the type described below, it is not
and forwards, in a nodding motion, and at the same acceptable to use less suitable equipment. For
time observe the counter. The counter should register instance, the rule attached to the traditional balance,
the greatest height when the head is tilted not too far to be found in doctor’s surgeries throughout the world,
forward or backwards. It is thus a relatively easy is completely unacceptable. It is usually extremely
matter to ensure correct positioning. unstable and imprecise. It is better in situations when
purpose-built machines are not available to use a lies on the supine-length table or in the neonatometer
vertical wall and a book held at right-angles on the such that the head is positioned in a supinated Frank-
subject’s head. With the subject properly positioned furt plane and the vertex of the head touches the fixed
the book can be placed on the head so that one side end of the apparatus. The head is held in this position
touches the wall and the other the top of the head. throughout the measurement by an observer who con-
A mark is then made on the wall at the inferior surface stantly checks that the correct position is being main-
of the book. The distance from the floor to the book can tained and that contact between head and headboard is
be measured with a tape measure after the child has constant. The second observer checks that the rest
moved away. of the body is relaxed and that the subject is not arch-
ing the spine or bending the knees. This observer holds
the feet such that the ankles are at right angles and the
HARPENDEN STADIOMETER toes not bending over to interfere with the cursor. The
cursor is then moved into contact with the feet and
This stadiometer is a counter recording instrument in slight pressure is applied to the ankles to straighten
which the counter gives a reading in millimeters over a the legs. This normally causes the head to be moved
range of 600–2100 mm. It is wall-mounted and made away from the headboard so that the other observer
of light alloy with a wooden headboard fixed to a metal must gently pull the head back into contact with it.
carriage that moves freely on ball-bearing rollers. This dual pulling of the subject has the same effect as
The face of the stadiometer is finished in plastic for deep breathing in the measurement of stature – to
easy cleaning. The complete instrument is 232 cm tall overcome diurnal variation in posture.
and weighs 12.7 kg. Depending on the age of the subject, various
These stadiometers have been in use in many problems arise during this measurement. Very young
clinics, hospital outpatient departments, and growth children will automatically bend the knees and the
centers for a number of years. When treated properly observer must apply downward pressure on them with
they give consistently accurate results, but the counter his or her forearm or elbow. The shoulders will also be
will break if the headboard is “raced” up or down the lifted off the board and the observer holding the head
backboard. For this reason it is recommended that the must use the index fingers to press them gently back
headboard is always locked or moved to its topmost into contact. It is sometimes necessary to release one of
position when not in use to prevent children or inex- the feet if the child fights so strongly that accurate
perienced adults from breaking the counter. Calibra- measurement is compromised and indeed in the very
tion of this instrument is straightforward and takes young this is often easier than trying to struggle with
very little time. A metal rod of known length is placed both feet. It should be emphasized that these problems
between the headboard and the floor so that it stands will arise more often if steps are not always taken to
vertically. If the counter does not record the correct relax the subject and familiarize it with the apparatus.
length of the rod then it may be loosened by undoing Cuddly toys suspended above the table or pictures on
the two metal retaining screws, and pulled away from the ceiling are good methods of attracting the attention
the main fiber cog of the carriage. In this position the of slightly older subjects but on the very young it is a
small metal cog of the counter may be turned until great help to allow the mother to lean over the child
the counter records the true length of the metal rod. and talk to it to reassure it.
The counter is then pressed against the back-plate
so that the teeth of the counter cog and carriage cog
engage and the retaining screws are tightened. The HARPENDEN NEONATOMETER
headboard is then moved up and down the backboard
a number of times to ensure that the counter continues The neonatometer is constructed as a rectangular
to give an accurate reading. If not, the counter must light-alloy frame with a curved metal headrest at one
be replaced. It is recommended that the instrument be end and a cursor carriage at the other. In common with
calibrated prior to every measuring session, particu- the other Harpenden instruments, the recording is by
larly if the stadiometer is left in a situation that allows a counter mechanism. The important addition to this
public access. instrument is the locking mechanism attached to
the cursor that locks the footboard when a pressure
of 0.5 kg is exerted against it. Such a mechanism pre-
SUPINE OR RECUMBENT LENGTH vents the observer from having to fight with the unruly
baby to maintain the leg in a straight position for
The measurement of supine length requires two obser- longer than a few seconds. The highly portable nature
vers, one to hold the head and the other to hold the feet of the instrument allows it to be placed over the recum-
and move the cursor. The subject (usually an infant) bent baby rather than disturbing the baby by placing
the subject inside the instrument. A short version is that the counter is reading correctly. If not, then suitable
made to fit inside most incubators. This version meas- adjustment can be made by loosening the retaining
ures over the range 180–600 mm compared with screws of the counter and turning its metal cog to the
188–750 mm for the standard model. This instrument correct measurement. The footboard is moved forwards
is necessary for any neonatal clinic but the general and backwards a few times to check the reliability, and
growth clinic, dealing with all ages of subjects, can if this is suspect a new counter is fitted.
perfectly well measure supine length accurately with
a longer, all age, instrument.
ABDOMINAL CIRCUMFERENCE;
WAIST CIRCUMFERENCE
HARPENDEN INFANTOMETER
Some confusion exists in the literature with regard to
This instrument was designed to fill the instrument gap the level of measurement. However, the minimum cir-
between neonates and school-age children, measuring cumference between the iliac crests and lower ribs
over a range of 300–940 mm. Bearing in mind the fact would appear to be the most reliable to determine.
that many studies on this age range of subjects are The general technique is for the subject to stand erect
set in the home rather than the growth centre, it is facing the observer with the arms away from the body.
designed as a portable instrument weighing about The tape is passed around the body and tightened at
6.75 kg. It is constructed of light-alloy with a flat head- the required level ensuring that it is horizontal and not
board and footboard fixed to a movable cursor and compressing the soft tissue.
counter recording mechanism. As with the neonat-
ometer, a locking device is fitted to aid measurement
when the subjects are active. BUTTOCK CIRCUMFERENCE; HIP
CIRCUMFERENCE; HIP GIRTH
HARPENDEN INFANT MEASURING TABLE Hip or buttock circumferences should be measured at

the level of the greatest protrusion of the buttocks
This instrument is the nonportable version of the when the subject is standing erect with the feet
infantometer. The base is constructed of light-alloy together. The subject stands sideways to the observer
with a fixed wooden headboard and footboard fixed with the feet together and arms folded. The observer
to a carriage and counter mechanism as with the other passes the tape around the body at the level of the most
instruments. There is no locking mechanism. The prominent protrusion of the buttocks so that it lightly
measuring range is 230–1200 mm so it is suitable for touches but does not compress the skin. In most cases
postneonates up to preschool children. The lack of a the subject will be dressed in underclothes which will
locking mechanism reflects the fact that the subject obviously affect the measurement, and so the observer
should be more co-operative and that the measuring should either provide standard thin undergarments or
position can be maintained for longer. insist that the subject be naked.
HARPENDEN SUPINE MEASURING TABLE TAPE MEASURES
This is the full-length supine table similar in construc- Many tape measures are available that are suitable for
tion to the stadiometer. It is recommended that this anthropometric use. Suitability depends on fulfilling
instrument is mounted on permanent wall-brackets, five criteria:
but adjustable legs may be supplied at an additional
cost. As in the infant measuring table, the head and 1. Flat cross-section. Tapes with a curved cross-
footboards are made of wood and the latter is fixed to a section are difficult to bend maintaining a smooth
cursor and counter mechanism. The measuring range outline.
is 300–2100 mm and so accommodates all age ranges 2. Millimeter graduations. The graduations must be
of children and adults. in centimeters and millimeters and preferably
marked on both edges of the tape. Thus at the cross-
over position it makes little difference whether the
CALIBRATION lead of the tape is above or below the reading.
3. Blank leader strip. The tapes should contain a
Calibration of all these instruments is very easy, and blank leader strip prior to the graduations com-
is similar to that employed for calibrating the stadi- mencing. This enables the observer to hold the
ometers. A metal rod of known length is used to ensure leading part without obscuring the zero value.
4. Metal or fiberglass construction. It has always been a midpoint between the lateral and medial surfaces
recommended that only steel tapes should be used of the arm. If the subject stands with his back to the
so that they did not stretch or deteriorate with use. observer and bends the left arm the observer can
Fiberglass tapes are now being manufactured that palpate the medial and lateral epicondyles of the
are guaranteed not to stretch. humerus. This is most easily done with the middle
5. Minimum length of 1 m. finger and thumb of the left hand, which will eventu-
ally grip the skinfold. The thumb and middle finger are
We have not described any single tape in detail because
then moved upwards, in contact with the skin, along
various types are available that fulfill most or all of
the vertical axis of the upper-arm until they are at a
these criteria.
level about 1.0 cm above the marked midpoint. The
skinfold is then lifted away from the underlying muscle
SKINFOLDS fascia with a sweeping motion of the fingers to the
point at which the observer is gripping the “neck” of
The technique of picking up the fold of subcutaneous the fold between middle finger and thumb. The skin-
tissue measured by the skinfold caliper is often fold caliper, which is held in the right hand with the
referred to as a “pinch” (Cameron, 1978, 1983, 1984), dial upwards, is then applied to the neck of the skinfold
but the action to obtain the fold is to sweep the index or just below the middle finger and thumb at the same
middle finger and thumb together over the surface of level as the marked midpoint of the upper arm. The
the skin from about 6 to 8 cm apart. This action may be observer maintains his or her grip with the left hand
simulated by taking a piece of paper and drawing a, and releases the trigger of the skinfold caliper with his
say, 10 cm line on its surface. If the middle finger and right to allow the caliper to exert its full pressure on the
thumb are placed at either end of this line and moved skinfold. In almost every case the dial of the caliper will
together such that they do not slide over the surface continue to move but should come to a halt within a
of the paper but form a fold of paper between them few seconds at which time the reading is taken to the
then that is the action required to pick up a skinfold. To last completed 0.1 mm. In larger skinfolds the caliper
“pinch” suggests a small and painful pincer movement may take longer to reach a steady state but it is unusual
of the fingers and this is not the movement made. for this to be longer than seven seconds. Indeed, if the
The measurement of skinfolds should not cause undue caliper is still moving rapidly it is doubtful that a true
pain to the subject, who may be apprehensive from the skinfold has been obtained and the observer must
appearance of the calipers and will tend to pull away either try again or admit defeat. This situation is only
from the observer, and, in addition, a pinching action likely to occur in the more obese subject with skinfolds
will not collect the quantity of subcutaneous tissue greater than 20–25 mm – that is, above the 97th centile
required for the measurement. In addition, the obser- of British charts. Within the 97th and 3rd centiles
ver must be careful to open the caliper prior to remov- skinfolds are relatively easy to obtain but they do
ing it from the fold of skin as failure to do this can require a great deal of practice.
result in a painful scratch for the participant.
The measurement of skinfolds is prone to many
sources of error. Location of the correct site is critical SUBSCAPULAR SKINFOLD (FIGURE 6.2)
(Ruiz et al., 1971), but greater errors may arise from
the consistency of subcutaneous tissue and the individ- The point of measurement is located immediately
ual way in which each observer collects the fold of below the inferior angle of the scapula. The subject
tissue. The novice should practice skinfold measure- stands with his or her back to the observer and his or
ments more than other anthropometric techniques. her shoulders relaxed and arms hanging loosely at the
The observer will thus obtain an awareness of how a sides of the body. This posture is most important
correct skinfold should “feel” and thus be aware of to prevent movement of the scapulae; if the subject
those occasions when a true skinfold is not being folded his or her arms, for instance, the inferior angle
obtained. of the scapula would move laterally and upwards and
therefore no longer be in the same position relative
to the layer of fat. The skinfold is picked up, as for
TRICEPS SKINFOLD triceps skinfold, by a sweeping motion of the middle
finger and thumb, and the caliper applied to the neck
The level for the triceps skinfold is the same as that for of the fold immediately below the fingers. The fold
the arm circumference – mid-way between the acro- will naturally be at an angle laterally and downwards
mion and the olecranon when the arm is bent at a right and will not be vertical. Once again, the dial of
angle. It is important that the skinfold is picked up both the caliper will show some movement that should
at a midpoint on the vertical axis of the upper-arm and soon cease.
dial 6 cm in diameter, with an almost linear scale and

divisions 150% of natural size.
HARPENDEN SKINFOLD CALIPERS
The Harpenden caliper (Tanner and Whitehouse, 1955)

resulted from the investigation of Edwards et al. (1955)
which recommended a design that included jaw faces of
size 6 15 mm, with well-rounded edges and corners,
pressure at the faces of 10 g/mm2 that does not vary
by more than 2.0 g/mm2 over the range of openings
2–40 mm, and a scale such that readings can be taken
to the nearest 0.1 mm.
These calipers may be calibrated by fixing them in
a bench clamp so that the jaws are parallel to the floor.
When a weight equivalent to 10 times jaw face area is
applied (90 g if the face is 6 15 mm as recommended)
the jaws should stay closed but if another gram is added
they should open to their fullest extent. There is always
6.2. The measurement of subscapular skinfold. some leeway around this figure but it has been demon-
strated that pressures between 9 g/mm2 and 13 g/mm2
make little difference to the skinfold reading.
SKINFOLD CALIPERS
HOLTAIN (TANNER–WHITEHOUSE)
Skinfold calipers are designed to measure the thick- SKINFOLD CALIPERS
ness of a fold of subcutaneous fat that has been picked
up at a specific landmark on the body by the anthro- The Holtain/Tanner–Whitehouse skinfold caliper is the
pometrist. The compressible nature of these skinfolds improved version of the Harpenden caliper. The design
means that the calipers have had to be designed to principle regarding jaw pressure, jaw face area, and
exert a constant pressure at all settings of the caliper readability are maintained but the Holtain caliper is
jaws. Constant-pressure calipers have been developed lighter than the Harpenden model and easier to hold,
in the United States and the United Kingdom that exert thus making repeated measurements less tiring and
a pressure of 10 g/mm2 of the jaw face area at all set- perhaps creating greater accuracy.
tings. We describe below the three clinic/research cali- Calibration may be checked in the same way as
pers that have been most commonly used and tested for the Harpenden model. Both models require little
for comparability although other calipers are available or no servicing beyond cleaning and care. There has
(e.g., the Lafayette skinfold calliper), but they have not, been some criticism of these calipers due to inconsist-
as yet, been extensively tested in clinical and research ency of spring pressure but if they are calibrated when
situations. first received and checked regularly thereafter, as with
all other instruments, no problems should arise.
LANGE CALIPER
DIAMETERS
The Lange caliper was introduced by Lange and
Bi-acromial diameter (Figure 6.3)
Brozek (1961) to provide for “persistent demands for
a light compact skinfold caliper.” It is composed of a Bi-acromial diameter is the distance between the tips
slender handle opposed by a thumb lever. Pressure on of the acromial processes. It is measured from the rear
this lever opens the jaws uniformly to a maximum of of the subject with the anthropometer. The position of
6 cm with a reading accuracy to þ1 mm. The lever is the lateral tips of the acromials is slightly different in
released to clamp these jaws on to the skinfold. The each subject and it is therefore necessary for the obser-
jaws have an area of approximately 30 mm2 and a ver to carefully palpate their exact position in each
constant pressure of 10 g/mm2 irrespective of the size subject before applying the instrument. This is most
of the skinfold, and they are pivoted to adjust automat- easily done with the subject standing with their back to
ically for parallel measurement of the skinfold. The the observer such that the observer can run his or her
reading is displayed by a fine pointer on a semicircular hands over the shoulders of the subject. This tactile
diameter, it is a good measurement procedure for the

observer to feel the position and shape of the crests
prior to applying the instrument, especially when the
subject has considerable fat deposits in that region.
The anthropometer is held as for bi-acromial diameter
and applied to the most lateral points of the iliac crests.
This will be more easily accomplished if the anthrop-
ometer is slightly angled downwards and the blades
applied to the crests at a point about 1 inch (2–3 cm)
from the tips. To ensure that the most lateral points
have been obtained it is a useful point of technique
to “roll” the blades over the crests. It will be seen on
the counter of the instrument that at a particular point
the distance between the crests is greatest; this is the
point of measurement.
ANTHROPOMETERS
Whilst anthropometers are not required for the meas-

urements described above the anthropometer is one of
the most versatile anthropometric instruments and can
6.3. The measurement of bi-acromial diameter. be used for measuring any linear dimension such as
height, sitting-height, or arm span in addition to limb
awareness of the positioning of the acromials is an segment lengths. Because of this versatility and useful-
important part of the measurement procedure because ness anthropometers should be chosen with care.
it allows the observer to be confident of the measure- Two basic designs of anthropometer are available; that
ment points when he or she applies the instrument. known as the Martin anthropometer, and the Harpenden
Having felt the position of the acromia and that the anthropometer.
subject’s shoulders are relaxed, the observer applies
the anthropometer blades to the lateral tips of the pro-
cesses. The anthropometer is held so that the blades rest MARTIN ANTHROPOMETER
medially to the index fingers and over the angle formed
by the thumb and index finger. The index fingers rest The Martin anthropometer is used universally in
on top of the blades, to counteract the weight of the physical anthropology. It is manufactured by GPM
bar and counter mechanism, and the middle fingers (Switzerland) and is thus sometimes referred to as
of each hand are free to palpate the measurement points the GPM anthropometer. The original version is com-
immediately prior to measurement. In this position posed of four metal rods with graduations in milli-
the observer can quite easily move the blades of the meters and centimeters engraved on them. A sliding
anthropometer so long as it is of the counter type. Other cursor runs the length of the rods when they are joined
anthropometers have too great a frictional force oppos- together to give a maximum reading of 2 m. Curved or
ing such easy movement and must be held by the straight blades may be inserted into the cursor housing
main bar so that the blades are remotely applied to the and fixed end so that the distance between them may
marked acromial processes. The blades must be pressed be read from the graduated main beam. The major
firmly against these protuberances so that the layer of disadvantage becomes apparent when this anthrop-
tissues which covers them is minimized. To ensure that ometer is used to measure children. In these situations
the correct measurement is being made it is a simple it is important to be able to feel the landmarks of the
matter to roll the blades up and over the acromia and body as the blades of the anthropometer are applied to
then outwards and downwards so that the observer the marked positions. It must be possible, therefore,
feels the blades drop over the ends of the acromia. to move the cursor housing whilst holding the tips of
the blades. The frictional forces involved in the Martin
anthropometer make this operation virtually impos-
Bi-iliac diameter
sible. A more recent version of the Martin instrument
The subject stands with their back to the observer, is now available from GPM. The main difference is that
feet together and hands away from his or her sides to the beam has a square rather than round cross-section
ensure a clear view of the iliac crests. As for bi-acromial but the problem with frictional forces still remains.
TABLE 6.1. Total technical error of measurement (TEM) reference values for height, weight, triceps, and subscapular
skinfold measurements split by gender and age group.
Male age groups (Years) Female age groups (Years)

Coefficient
Measurement of reliability 1–4.9 5–10.9 11–17.9 18–64.9 65þ 1–4.9 5–10.9 11–17.9 18–64.9 65þ
Height (cm) 0.095 0.0103 0.0130 0.0169 0.0152 0.0152 0.0104 0.0138 0.0150 0.0139 0.0135
0.099 0.0046 0.0058 0.0076 0.0068 0.0068 0.0047 0.0062 0.0067 0.0062 0.0060
Weight (kg) 0.095 0.21 1.20 5.94 13.06 10.80 0.22 1.61 8.66 16.74 11.70
0.099 0.04 0.24 1.19 2.61 2.16 0.04 0.32 1.73 3.35 2.34
Triceps 0.095 0.61 0.97 1.45 1.38 1.29 0.65 1.05 1.55 1.94 1.86
skinfold 0.099 0.28 0.43 0.65 0.62 0.58 0.29 0.47 0.69 0.87 0.83
(mm)
Subscapular 0.095 0.43 0.87 1.55 1.79 1.74 0.47 1.08 1.74 2.39 2.27
skinfold 0.099 0.19 0.39 0.69 0.8 0.78 0.21 0.48 0.78 1.07 1.02
(mm)
Source: Adapted from Ulijaszek and Kerr (1999).
HARPENDEN ANTHROPOMETER Vertex
The Harpenden instrument was designed to overcome

this problem of frictional forces when holding the Frankfurt plane
instrument by the tips of the blades. The cursor runs
on miniature ball-bearing rollers allowing a free move-
ment that is without crossplay. As with the other Har-
penden instruments this is a counter display instrument Acromion process
giving readings over the range 50–570 mm. As with the
Martin anthropometer, beam extensions may be added Sternum
to the main bar but because of the counter display,
constants, equivalent to the length of the beams, must Xiphoid process
be added on to the counter reading.
ACCEPTABLE ERROR LIMITS Iliac crest
Following on from the methods section, Table 6.1

provides a summary of the accepted upper limits for
total TEM for two levels of reliability (95% and 99%)
for a number of anthropometric measurements split Ischial tuberosities
by gender and chronological age. These TEM values
provide a reference for anthropometrists on which to 6.4. Skeletal landmarks of the skull, thorax, and pelvic girdle.
base decisions about the acceptability of measurement
error within their study (Ulijaszek and Kerr, 1999). between individuals means that sometimes the acro-
mial angle is not the most lateral point. Palpation
of the most lateral part may best be performed by
SURFACE LANDMARKS running the anthropometer blades laterally along the
shoulders until they drop below the acromia. If the
Acromion process (lateral border of the acromion)
blades are then pushed medially the most lateral part
(Figures 6.4 and 6.5)
of the acromia must be closest to the blades and
The acromion projects forwards from the lateral end may be felt below the surface marks left by the blades.
of the spine of the scapula with which it is continuous. There is the possibility of the inexperienced anthropo-
The lower border of the crest of the spine and the metrists confusing the acromio-clavicular joint with
lateral border of the acromion meet at the acromial the lateral end of the acromion. Great care must be
angle which may be the most lateral point of the acro- taken to distinguish between these two landmarks
mion. Great diversity in the shape of the acromion prior to measurement.
Medial Lateral Posterior Anterior

Iliac crest
Acromion process
Anterior superior iliac spine
Scapula
Medial border
Greater trochanter Pubic tubercle
Inferior angle Humerus
Femur
Olecranon
Medial epicondyle Lateral epicondyle
Head of the radius
Lateral epicondyle Patella

Radius
Ulna
Ulna styloid Fibula

Distal end of the radius Tibia
Radial styloid
Lateral Malleolus
6.5. Skeletal landmarks from posterior view of scapula and arm.

6.6. Skeletal landmarks from lateral view of pelvic girdle and leg.
Anterior superior iliac spine (Figure 6.6)

This is the anterior extremity of the ilium, which
projects beyond the main portion of the bone and Vertex
may be palpated at the lateral end of the fold of the
groin. It is important to distinguish the iliac crest from
the anterior spine when measuring bi-iliac diameter.
Glabella
Maximal occipital point
GO
Biceps brachii Orbitale
FP
The biceps brachii is the muscle of the anterior aspect Lower orbit Mastoid process
of the upper arm. Its two heads, the short and the long,
arise from the coracoid process and the supraglenoid Gonion
Lower mandible
tubercle of the scapula respectively and are succeeded
by the muscle bellies before they end in a flattened
tendon that is attached to the posterior part of the 6.7. Skeletal and surface landmarks of the head. FP, Frankfurt
plane; GO, Glabella-occipital plane.
radial tuberosity. When relaxed the muscle belly has
its greatest bulge towards the radius, but when con-
tracted with the arm flexed the belly rises to a point
nearer the shoulder. Thus relaxed and contracted arm
External auditory meatus (Figure 6.7)
circumferences, taken at the maximum bulge of the
muscle, are not at exactly the same level. This landmark, used to obtain the Frankfurt plane, is
also called the external acoustic meatus and leads
to the middle ear from the external auricle. In terms
Distal end of the radius (Figure 6.5)
of a surface landmark it is therefore simply present as a
This is the border of the radius proximal to the distal- hole in the external ear and may therefore be easily
superior borders of the lunate and scaphoid and seen. The tragus, the small curved flap that extends
medial to the radial styloid. It may be palpated by posteriorly from the front of the external ear, overlaps
moving the fingers medially and proximally from the the orifice of the meatus and may be used to gauge the
radial styloid (see Radial styloid, below). level of the orifice.
Femur epicondyles (Figure 6.6) forms a conspicuous blunt projection on the medial
aspect of the elbow when the arm is held at the side
The lower end of the femur consists of two prominent
of the body with the palm facing forward. The lateral
masses of bone called the condyles which are covered by
epicondyle may be palpated opposite and a little above
large articular surfaces for articulation with the tibia.
the medial epicondyle.
The most prominent lateral and medial aspects of the
condyles are the lateral and medial epicondyles. These
may be easily felt through the overlying tissues when the Iliac crest (Figures 6.4 and 6.6)
knee is bent at a right angle, as in the sitting position.
This may be palpated as the most superior edge of
If the observer’s fingers are then placed on the medial
the ilium and may be easily felt through the overlying
and lateral aspects of the joint the epicondyles are the
soft tissue. Greater difficulty will be experienced with
bony protuberances immediately above the joint space.
the more obese subject but it is quite possible with the
anthropometer blades to compress the tissue and feel
Frankfurt plane (Figure 6.7) the crest.
This plane, used extensively in anthropometric meas-
urement, is obtained when the lower margins of the Malleoli (Figure 6.6)
orbital openings and the upper margins of the external
The medial malleolus is the bony protuberance on the
acoustic (auditory) meatus lie in the same horizontal
medial side of the ankle. It is the inferior border of this
plane. The supinated Frankfurt plane, used in the
malleolus that is palpated and used as a landmark for
measurement of recumbent and crown- rump length,
the measurement of tibial length.
is vertical rather than horizontal.
Mastoid process (Figure 6.7)

Gastrocnemius
This is the conical projection below the mastoid por-
This is the most superficial of the group of muscles at
tion of the temporal bone. It may be palpated immedi-
the rear of the lower leg and forms the belly of the calf.
ately behind the lobule of the ear and is larger in the
male than in the female.
Glabella (Figure 6.7)
This landmark is in the midline of the forehead
Mid-axillary line
between the brow ridges and may be used as the most
anterior point of the head. The axilla is the pyramidal region situated between the
upper parts of the chest wall and the medial side of
the upper arm. The mid-axillary line is normally taken
Gluteal fold
as the line running vertically from the middle of this
This fold or furrow is formed by the crossing of the region to the iliac crest.
gluteus maximus and the long head of the biceps
femoris and semitendinosus. It may therefore be
Mid-inguinal point (inguinal crease)
viewed from the lateral aspect or the posterior aspect
as the crease beneath the buttock. In some subjects, The inguinal ligament runs from the anterior superior
perhaps because of a lack of gluteal development, a iliac spine to the pubic tubercle at an angle of 35–40
crease may not be present. In this case the level of the degrees and is easily observed in all individuals. The
gluteal fold is judged from the lateral profile of the midpoint between the anterior spine and the pubic
buttocks and posterior thigh. tubercle on the line of the inguinal ligament is taken
as the mid-inguinal point.
Head of the radius (Figure 6.5)

Midpoint of the arm
This may be palpated as the inverted, U-shaped bony
protuberance immediately distal to the lateral epicon- The midpoint of the arm, used for arm circumference,
dyle of the humerus when the arm is relaxed with the is taken as the point on the lateral side of the arm
palm of the hand facing forwards. midway between the lateral border of the acromion
and the olecranon when the arm is flexed at 90 degrees.
This may be most easily determined by marking the
Humeral epicondyles (Figure 6.5)
lateral border of the acromion and applying a tape
These are the nonarticular aspects of the condyles on the measure to this point. If the tape is allowed to lie over
lower surface of the humerus. The medial epicondyle the surface of the arm, the midpoint may easily be
calculated and marked. Alternatively, tape measures Sternum (Figure 6.6)

do exist with a zero midpoint specifically designed to
The sternum or breastbone is the plate of bone inclined
determine this landmark. It has been common to refer
downwards and a little forwards at the front of the chest.
to this point, and the circumference or girth at this
It is composed of three parts; the manubrium at the top,
level, as the “mid upper-arm” landmark/circumference.
the body or mesosternum at the centre, and the xiphoid
This terminology is specifically not used here because
process at the lower end. The mesosternum and xiphoid
it is anatomically incorrect to describe this area the
process are important landmarks in anthropometry.
brachium or arm as the “upper-arm”. Anatomically
The mesosternum is marked by three transverse ridges
the brachium (arm) and the ante-brachium (forearm)
or sternabrae and the junction between the third and
form the upper limb.
fourth sternabrae form a landmark in chest measure-
ment. The fourth sternabrae may not be easily palpated
Occiput (Figure 6.7) but the junction lies below the more easily palpated third
sternabrae. The xiphoid process may be palpated by
The occipital bone is situated at the back part and
following the line of the sternum to its end. The sternum
base of the cranium. The occiput is the most posterior
is considerably larger in males than in females.
part of this bone and may be clearly seen from the side
view of the subject.
Trapezius
The Trapezius is a flat, triangular muscle extending
Olecranon (Figure 6.5)
over the back of the neck and the upper thorax.
The olecranon is the most proximal process of the ulna
and may be easily observed when the arm is bent as the Triceps
point of the elbow.
The triceps muscle is the large muscle on the posterior
side of the upper arm. When the arm is actively
Patella (Figure 6.6) extended two of the three triceps heads may be seen
The patella is the sesamoid bone in front of the knee as medial and lateral bulges.
joint embedded in the tendon of the quadriceps
muscle. It is flat, triangular below and curved above. Trochanters (Figure 6.6)
When the subject is standing erect its lower limit lies The greater and lesser trochanters are projections at
above the line of the knee joint and its upper border the proximal end of the femur. The lesser trochanter
may be palpated at the distal end of the quadriceps cannot be palpated on the living subject because it lies
muscle. on the posterior surface of the femur and is covered by
the large gluteal muscles. The greater trochanter, how-
Pinna of the ear ever, is palpable as the bony projection on the lateral
surface of the upper thigh approximately a hand’s
The pinna of the ear is more correctly called the lobule breadth below the iliac crest.
and is the soft part of the auricle that forms the ear-
lobe. Ulna styloid (Figure 6.5)
The styloid process of the ulna is present as a short,
Radial styloid (Figure 6.5) rounded projection at the distal end of the bone. It may
The radial styloid is the distal projection of the lateral be easily palpated on the posterior-medial aspect of
surface of the radius. It extends towards the first the wrist opposite and about 1 cm above the styloid
metacarpal and may be palpated as a bony projection process of the radius.
on the lateral surface of the wrist when the hand is
relaxed. Umbilicus
The umbilicus, or naval, is clearly observable in the centre
Scapula (Figure 6.5) of the abdomen. It is variable in position, lying lower in
the young child due to lack of abdominal development.
The scapula is the large, triangular flattened bone on
the posterolateral aspect of the chest, and is commonly
Vertex of the skull (Figure 6.7)
known as the shoulder blade. Its medial border slopes
downwards and laterally to the inferior angle that may This is the top-most point of the skull and theoretically
be easily palpated, and lies over the seventh rib or comes into contact with the stadiometer headboard
seventh intercostal space when the arm is relaxed. when height is being properly measured. With the head
in the Frankfurt plane the vertex is slightly posterior to OTHER APPLICATIONS

the vertical plane through the external auditory meatus
and may be easily palpated. Of course, the use of anthropometry for the assessment
of child growth and development is only one applica-
tion and has been used here for illustration purposes.
TECHNOLOGICAL ADVANCES IN Anthropometry is regularly used in a large number
ANTHROPOMETRIC ASSESSMENT of other contexts such as the assessment of body
composition and nutritional status (see the following
Whilst traditional anthropometry has many benefits, chapter for a detailed summary), directional and fluc-
it also has limitations in that it is subject to a number tuating asymmetry, digit ratios, and for diagnosing
of potential sources of error, it is time consuming and diseases such as body dysmorphia. Asymmetry in bilat-
expensive to measure large numbers of participants eral anatomical structures such as facial features,
(Azouz et al., 2006), and it provides limited informa- hands, and feet is commonplace, for example one hand
tion about body shape (Robinette et al., 1997). The use my be slightly bigger than the other, and is termed
of semi- and fully automated data acquisition equip- directional asymmetry if the trait is consistently larger
ment is becoming increasingly commonplace. There on one side of the body within a population. In con-
has been rapid advancement of automated anthropo- trast, fluctuating asymmetry refers to traits that are not
metric data collection instruments in recent decades, unidirectional within a population. It is thought that
in particular, the advancement of digital human genetic and/or environmental insults influence an
models which are generated from three-dimensional individual’s ability to maintain bilateral symmetry in
(3D) whole body scans. From these digital models, morphological traits during growth and development.
one-dimensional (1D) measurements of body dimen- Directional asymmetry is a measure of laterality and
sions such as lengths (circumferences are more prob- is thought to be driven by exposure to sex steroids
lematic) can be derived (Robinette and Daanen, 2006) whereas fluctuating asymmetry is thought to reflect
quickly and accurately for large numbers of partici- developmental instability (Martin et al., 2008). Differ-
pants. In addition, new or different measurements ences in bilateral anatomic traits can easily be
can be derived from stored digital images post clinic assessed using standard anthropometric techniques.
or field appointment. In the Civilian American and A common bilateral trait examined using anthropom-
European surface anthropometry resource (CAESAR) etry is the 2D:4D ratio (a ratio of the length of the
study, some 4400 participants (aged 18–65 years) from index and ring fingers on one hand), which is sexually
the United States, the Netherlands, and Italy were dimorphic trait established in utero and has been
scanned and digital body images generated (Robinette associated with sexuality, behavior, and health (Man-
et al., 2002). From the scan data, 60 1D linear dimen- ning, 2002). Finally, anthropometry can be used in
sions were derived and a further 40 measures were clinical settings to help physicians diagnose certain
collected using standard anthropometric techniques disorders, for example body dysmorphic disorder
(i.e., with tape measures and calipers). In a study com- (BDD). A person with BDD has a preoccupation with
paring the precision of the CAESAR scan-derived 1D an imagined/nonexistent or slight defect in their
measurements with the allowable errors reported in appearance (most commonly skin, hair, and/or facial
the US Army ANSUR traditional anthropometric survey features) which usually begins during adolescence
(Gordon et al., 1989); Robinette and Daanen (2006) (Albertini and Phillips, 1999). Anthropometry can be
showed that the CAESAR measures were more reliable used by clinicians to help diagnose BDD by establish-
than the traditional measures reported in the ANSUR ing if the complaints of the patient are medical in
survey, in that mean absolute differences (MAD), nature (i.e., fall outside of expected ranges for a popu-
indicating the error between repeated measures of the lation) or psychological as they cannot be explained by
same participant, were on average less than 5 mm for physical disease, substance abuse, or other mental
the CAESAR measurements compared to an average disorders.
allowable error of 6.2 mm for the ANSUR survey. Robin-
ette and Daanen (2006) concluded that these types of
scan-extracted 1D linear measurements were as good if DISCUSSION POINTS
not better than traditionally collected anthropometric
measurements. One must however acknowledge that 1. How do you decide to exclude potentially errone-
the CAESAR study did not use scan-derived measures ous data points within an analysis dataset?
for circumferences as Perkins et al. (2000) have shown 2. Why is it important to have quality control checks
that scan-extracted circumferences are more error in studies using anthropometric measurements?
prone and less reliable compared to traditional anthro- 3. What different considerations apply to the cleaning
pometric assessments of body circumference. of cross-sectional as opposed to longitudinal data?
4. What principles should be employed to decide on Hertzberg, T. (1968). The conference on standardization of
the level of precision required in any particular anthropometric techniques and terminology. American
research design? Journal of Physical Anthropology, 28, 1–16.
5. What are the advantages and disadvantages of using Hrdlička, A. (1947). Hrdlicka’s Practical Anthropometry, 3rd
automated anthropometric data collection tools? edn. Philadelphia: Wistar Institute.
International Children’s Centre (1977). Growth and Develop-
ment of the Child: International Children’s Centre Coordinated
Studies Publications Index 1951–1976. Paris: International
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7 Energy Expenditure and Body
Composition: History, Methods,
and Inter-relationships
Peter S. W. Davies and Alexia J. Murphy
ENERGY EXPENDITURE AND BODY isolated system the energy of the system remains con-
COMPOSITION stant.” This classical description was based upon the
earlier work of a compatriot of Helmholtz, Robert
Energy expenditure and body composition are closely Mayer. Secondly, Germain Hess, around the same
related. The energy expenditure of virtually any animal time, described the law of constant heat summation,
can be measured but of course this energy is not being i.e., the heat released by a number of reactions is inde-
expended equally throughout the body. Organs such as pendent of the chemical pathways involved and is only,
the brain, liver, heart, and kidneys have, relative to their and totally, dependent upon the end products. This is
weight, a high-energy output, whilst, for example, often simply referred to as Hess’s law. These two basic
muscle mass, although being a substantial component laws enable us to study energy metabolism and hence
of body weight, has on a per kilogram basis a lower energetics in the human by calorimetry, the measure-
energy output. When these individual organs or organ ment of heat production.
systems are combined, essentially the fat free mass The pioneers in this field used animals to attempt
(FFM) is the major contributor to energy expenditure, to understand the relationships between heat produc-
with the remaining fat mass (FM) being more energetic- tion, metabolism, and life. One of the first important
ally inert. Thus, methods of studying both energy metab- questions to be asked at this time was what is the
olism and body composition have often developed in source of animal heat? This question posed by the
parallel, with the need being to adjust one for the other. French Académie des Sciences in 1822 as a subject for
This chapter aims to provide a history of some of those a prize, led two scientists, Despretz and Dulong to inde-
methods as well as some theoretical and practical infor- pendently devise, construct and describe the first true
mation regarding their use before finally considering calorimeters. These calorimeters were, however, based
how they relate and how the relationships influence upon Lavoisier’s apparatus that had been designed and
our understanding of both areas of biology. then neglected by science some 40 years earlier to
measure the heat production of small mammals. The
equipment devised by both Despretz and Dulong con-
INTRODUCTION TO THE STUDY OF ENERGY sisted of a small chamber surrounded by a water
METABOLISM jacket. When placed in the chamber heat produced by
the animal was transferred to the water and the tem-
There are a number of fundamental maxims that perature change recorded. Any gases produced by
underpin large areas of modern science. It is signifi- animal were also collected for analysis. The techniques
cant that many of these laws and principles were available for respiratory gas analysis were enhanced by
described in a concise form in the eighteenth and nine- the work of Regnault and Reiset in order to study the
teenth centuries when some of the great men and effect of the consumption of differing foods on expired
women of science were laying down the foundations gas composition. This area of study led to the design of
and laws that govern much of modern physical and the first closed-circuit indirect calorimeter, that is,
biological studies. There are two such laws that form equipment that would allow the measurement, or at
the basis of studies pertaining to energy metabolism least calculation, of energy expenditure, by the deter-
and hence energetics in the human. Firstly, Hermann mination of carbon dioxide production, oxygen con-
Helmholtz described in 1847 the law of the conserva- sumption, and nitrogen balance. This magnificently
tion of energy thus; “in all processes occurring in an designed and constructed piece of apparatus used
113
114 Peter S. W. Davies and Alexia J. Murphy
three large volumetric flasks as the supply of air, and still used today. A significant publication around this
thus was a “closed” system. It was used to measure the time appeared in the Journal of Physiology (London) in
effect of differing foodstuffs on expired gases in dogs, which Weir described an equation for the mathemat-
pigeons, and other animals. Initial scientific observa- ical conversion of data relating to oxygen consumption
tion by these workers and others then began to give and carbon dioxide production to a measure of energy
way to experimentation. By 1860, the effect of starva- expenditure (Weir, 1949). This equation continues to
tion on energetic, or metabolism as it was then termed, be widely used today.
was being studied in Munich by Bischof and Voit. In the first decade of the twentieth century ques-
These experiments led to the development of further tions were posed relating to energetics and energy
apparatus. Thus, the group in Germany built the first metabolism in health and disease, and the possible
open-circuit indirect calorimeter, which in fact was clinical applications of such knowledge was being
large enough to accommodate a man, if not in great investigated notably in North America. Large calorim-
comfort. In this case atmospheric air was allowed into eters were built for this purpose by Williams, Lusk, and
the chamber and hence the term “open” calorimeter. Dubois in order to study what were termed “metabolic
The measurement of energetics by calorimetry was disorders.” About this time, as well, the first work
now beginning to bifurcate. While Rubner spent much involving infants and children was reported, notably
time and effort perfecting a direct calorimeter to meas- the studies of Benedict and Talbot (Benedict, 1914;
ure heat production in dogs, Pettenkofer endeavored to Benedict and Talbot, 1914; Benedict, 1919). These two
perfect indirect calorimetry. Once it was recognised that pioneers of energy metabolism studies in infancy and
the two approaches could be complementary rather childhood developed an indirect calorimeter for the
than antagonistic it became important to know the measurement of basal metabolic rate in early infancy.
extent to which they gave the same answer! This ques- Small infants were kept in this chamber for a number
tion was tackled by Rubner in 1894 using dogs as the of hours until, in the words of Benedict (1919), “the
experimental animal. There was agreement of better child became accustomed to the conditions and fell
than 1% between the two methodologies. The equiva- asleep.” Larger chambers were later built to accommo-
lent experiment was, however, not carried out in date older children. The largest of these chambers was
humans for almost a further10 years. However, when installed at the New England Home for Little Wander-
completed in 1903 the classic work of Atwater and Bene- ers, where children up to the age of 14 could be meas-
dict (1903) showed an equal measure of agreement. ured. The chamber was designed to have a minimal
The value of being able to assess energy expend- dead space, with only a small window allowing illumin-
iture in order to estimate energy requirements was ation into the chamber and visibility out of it.
soon appreciated by the meat and livestock industry, Larger chambers that allow the analysis of respira-
and much of the incentive for the creation of improved tory gases are now available, which are large enough to
direct and indirect calorimeters was shown by the food allow a certain amount of activity or “free living.”
industry. In human studies the necessity for confine- Nevertheless such cambers, with volumes in the order
ment in a closed chamber, regardless of size, in order of 30 000 L, require periods of up to 8 hours before
to assess energy expenditure was causing frustration equilibrium is reached and measurements can be
for investigators. By the beginning of the twentieth taken. Fast-response algorithms have been developed
century portable apparatus was being designed in to enable results to be achieved more quickly, but such
order to study energy expenditure and energy balance chambers cannot still be used easily in many popula-
during physical activity. The first truly successful tions such as infants, children, and the sick.
method of assessing energy output during physical A significant advancement in the ability to study
activity was developed by Douglas (1911). His system, energetics in humans in what has been termed the
basically still in widespread use today, used a large “free living” situation occurred in the 1980s with the
rubber-lined bag, usually carried on the subject’s back, refinement of the so called doubly labeled water tech-
into which all expired air was collected. The volume of nique for calculating the carbon-dioxide production rate
the expired gases collected as well as the composition using two stable isotopes in the form of water (Schoeller
of those gases allowed a calculation of both carbon and Van Santen, 1982; Coward et al., 1988). This method
dioxide production rate and oxygen consumption. is described in further detail later in this chapter.
The major limitation then, as today, was the size of
the bag. The logical development of this system
occurred many years later. The expired gases were MEASUREMENTS OF ENERGY EXPENDITURE
not collected but metered whilst in situ with a small
Direct calorimetry
sample being kept for gas analysis. This was then the
basis of the Kofranyi–Michaelis instrument (Kofranyi There are few if any large direct calorimeters still in
and Michaelis, 1940). Again, this type of apparatus is use. They were technically demanding and expensive to
Energy Expenditure and Body Composition 115
maintain and whilst in some ways they are the true (value at standard temperature and pressure [STP]).
calorimeters, in that they actually measured heat However, it cannot be guaranteed that all the alcohol
production by a variety of different methods, their has been burnt and that none has been lost to evapor-
disadvantages outweighed their advantages. Whilst ation when using this approach.
sometimes referred to as the gold standard for the
assessment of energy expenditure the method has been
superseded by other less difficult and sometimes less DOUBLY LABELED WATER
expensive approaches.
This method is, in many ways an example of indirect
calorimetry. The doubly labeled water technique is the
INDIRECT CALORIMETRY first noninvasive method available to measure daily
energy expenditure accurately (Schoeller and Van
Indirect calorimetry in various forms continues to be Santen, 1982). This method involves enriching the
used in many research centers and clinical situations. body water with isotopes of oxygen (oxygen-18) and
Indirect calorimetry, as its name implies, does not hydrogen (deuterium) and then measuring the
measure heat production but is based on the measure- difference in turnover rates of these isotopes in body
ment of oxygen consumption and carbon dioxide pro- fluid samples. The difference in the rate of turnover
duction that occurs with the oxidization of protein, of the two isotopes can be used to calculate the
carbohydrate, fat, and alcohol. The amount of oxygen carbon-dioxide production rate. The mean respiratory
consumed and carbon dioxide produced is used in the quotient (carbon-dioxide production rate/oxygen pro-
Weir equation to calculate the amount of energy duction rate) is assumed and therefore the oxygen pro-
expended (Weir, 1949). duction rate and consequently energy expenditure can
There are still a number of large indirect calorim- be calculated.
eters in operation that allow measurements of energy Doubly labeled water is a preferred method of
expenditure to by made in humans for periods of typ- energy expenditure measurement as it requires limited
ically between 24 and 72 hours. Such indirect calorim- subject effort, is noninvasive, and measurements are
eters can be found, for example, at the University of performed in real life conditions. The disadvantages of
Maastricht in the Netherlands and the University of the method are that it is expensive, requires complex
Wollongong in Australia. These chambers are much analysis, and is not suitable for large population stud-
improved in many ways in comparison to the early ies. The sources of error of the method include analyt-
chambers described previously, and now contain ical errors with mass spectrometry, biological variation
amenities such as televisions, telephones, computers, in the isotope enrichment and isotope fractionations,
etc. These apparatus require careful calibration and and the assumptions of the method. The method is in
maintenance. use in a relatively small number of centers but has been
Measurements of energy expenditure, usually at validated against indirect calorimetry in a number of
rest, over significantly shorter periods can be achieved differing populations from premature infants to adults
with any one of an array of commercially available (Schoeller and Van Santen, 1982; Roberts et al., 1986;
apparatus. Facemasks, mouthpieces, or ventilated Schoeller et al., 1986; Coward, 1988).
hoods are the most popular and prominent methods
of achieving gas collection. Such technology can be
Heart rate and activity monitoring
used in infants, children, and adults both in health
and in disease (Singhal et al., 1993; Wells and Davies, The prediction of total energy expenditure from heart
1995). Other apparatus are designed for measuring the rate monitoring and activity monitors are basic field
energy cost of activity and thus energy expenditure in a measures. Heart rate monitoring is a useful field
range of situations can be assessed using this method- method where actual energy expenditure is derived
ology (Littlewood et al., 2002). In young children this from the regression of oxygen production versus heart
can be challenging but is achievable. Many of the rate. Each individual needs to be “calibrated,” that is,
newer pieces of apparatus have been validated against an individual relationship between heart rate and
existing indirect methods (Duffield et al., 2004; Perret oxygen consumption needs to determined. Following
and Mueller, 2006). this the heart rate monitor is then worn, sometimes for
The traditional and sometimes termed gold stand- many days, after which the individual heart beats are
ard method for calibration of indirect calorimeters is related to oxygen consumption and hence energy
the alcohol burn. This method, first designed many expenditure. The advantage of this method is that it is
years ago, by Carpenter and Fox (1923), is based on inexpensive, in comparison with doubly labeled water
the fact that 1 g of ethanol consumes 1.70 L of oxygen for example, but the disadvantages of this method are
and produces 0.97 L of carbon dioxide when burnt that factors other than oxygen production affect heart
rate. Also it is inaccurate at low levels of activity, is weighing system that included adjustment for residual
time consuming, and is sometimes seen as having a trapped air in the lungs (Behnkeet al., 1942). Another
significant participant burden. Nevertheless, the researcher that contributed to the early era of body
method has been validated against the doubly labeled composition research was Francis Moore. His research
water technique and is an accepted field method in the 1940s was the first to focus on the study of
(Livingstone et al., 1990, 1992). biochemical phases and ignited the surge of research
Activity monitors vary considerably from ped- into this area of body composition methods (Moore,
ometers to significantly more complicated devices that 1946).
aim to predict energy expenditure. The pedometer The late 1950s saw investigation of whole body
simply measures steps or movement in one direction, counters to measure total body potassium (TBK) and
whereas accelerometers can measure body acceleration the link between the body’s potassium-40 content and
in several planes. In accelerometry, an equipment- FFM was reported (Anderson and Langham, 1959;
specific algorithm is often used to convert the activity Allen et al., 1960; Forbes et al., 1961). In 1961 Forbes
counts in each vector to energy expenditure. Although and colleagues estimated fat and lean contents using
this method is simple and can be used in population whole body counting (Forbes et al., 1961). Also in the
studies, there are limitations with this method when early 1960s, Thomasset (1962, 1963) introduced the
attempting to quantifying total energy expenditure bioelectrical impedance analysis (BIA) method, evolv-
because of the need to relate physical activity ing from Pace and Rathburn findings in 1945 that water
“counts” to the energy cost of the various activities is not present in stored fat and that water occupies a
undertaken. fixed fraction of the FFM (Pace and Rathburn, 1945).
By the early 1970s many new medical methods were
Introduction to body composition methods being introduced for body composition assessment –
Body composition concepts have always been a vital in vivo neutron activation (Anderson et al., 1964),
component of biological studies. The earliest record of computerized tomographic (CT) imaging (Hounsfield,
scientists’ investigating body composition was in the 1973), and total body electrical conductivity.
1850s when European chemists were developing chem- From 1979, Steve Heymsfield led the reintroduc-
ical analytical techniques in animal tissues. By the tion of anatomy to the research of body composition
early 1900s fetuses and newborns were being chem- by identifying the value of CT scans to provide organ-
ically analysed for Na, K, Cl, Ca, P, N, water, and specific tissue volumes (Heymsfield et al., 1979). In
fat (Moulton, 1923; Givens and Macy, 1933; Iob and 1981, Peppler and Mazess introduced the concept of
Swanson, 1934). In 1906 the German physiologist, dual photon absorptiometry (Peppler and Mazess,
Adolf Magnus-Levy, reported the importance of 1981), and in 1984 Foster and colleagues reported the
expressing body tissue composition in a fat free basis use of magnetic resonance imaging (MRI) as a body
and the concept of fat free body mass was formed composition measurement (Foster et al., 1984). With
(Magnus-Levy, 1906). This was an important new con- the development of these new techniques, by the 1990s
cept that continues to influence body composition stud- researchers were able to measure both the anatomical
ies to this time. Another important and long-lasting and chemical content of the body, thus gaining the best
concept, that of relating height and weight to adjust possible insight into human body composition.
one for the other, was also first described around this Body composition research in the last 20 years has
time when, in 1871, Queletet reported that weight been strongly focused on improving techniques and
increased in proportion to height squared, which is the extending their validity to clinical and specific popula-
basis of the body mass index (Quetelet, 1871). tions. The most recent development of a new body
In the 1930s, researchers collected anthropometric composition device is based on one of the oldest prin-
measurements providing the basis of today’s reference ciples of body composition research, densitometry.
data and worked towards developing indirect methods Underwater weighing was the only available measure-
of determining human body composition. Albert ment of densitometry until recently, when in 1995 an
R. Behnke was a pioneer in the area of body compos- instrument based upon air displacement, plethysmo-
ition research, with densitometry being one of the first graphy, became available (McCrory et al., 1995). The
indirect body composition methods. In 1933, Behnke Bod Pod® (Life Measurements Instruments, Inc., Con-
and colleagues proposed that fat could be estimated cord, CA) is suitable for use in adults and children, and
from a measurement of body density. In 1942 they in 2003 the Pea Pod® (Life Measurements Instruments,
reported the assumptions inherent to densitometry, Inc., Concord, CA) was introduced for infants up to six
that the chemical composition of FFM is different to months of age (Urlando et al., 2003). Another method
FM and is assumed to remain constant and is known recently developed uses resonant cavity perturbation
(Behnke et al., 1933, 1942). In 1942, Behnke and col- techniques to measure total body water (TBW) (Stone
leagues, again, were the first to develop an underwater and Robinson, 2003).
MEASUREMENTS OF BODY COMPOSITION Another, less commonly applied 4C model, divides

the body into three cellular components: body cell
Compartmental models of body composition
mass (BCM), extracellular fluid (ECF) and extra-
Two compartment cellular solids (ECS). For this model the BCM is meas-
The two-compartment (2C) model is the basic division ured by TBK, ECF by bromide or sulfate dilution, and
of the body compartments into fat, FM, and FFM. Fat ECS by total body calcium or BMC. The disadvantages
free mass is defined as all the tissues of the body minus of the 4C models are that the techniques are technically
the extractable fat, which is termed the FM. The 2C demanding, expensive, and not widely available in all
model has been used in body composition research since setting.
the 1940s and continues to play a vital role (Behnke
et al., 1942). The most commonly used 2C models are
based on the measurements of body density, TBK, and METHODS OF BODY COMPOSITION
TBW. The 2C model assumes that the chemical compos-
Anthropometry
ition of FFM body tissue stores remain constant; how-
ever, it is known that the composition of the FFM is As described in the previous chapter, anthropometric
variable in children and disease states Therefore the 2C measures are amongst the oldest body composition
model is inadequate for individuals who deviate from methods still applied and allow the evaluation of body
the healthy adult constants on which they are based. composition outside the laboratory. Anthropometry
includes measurements of weight, height, circumfer-
ences, and skinfolds. These methods are often used as
THREE COMPARTMENT they are simple, inexpensive, safe, and portable, how-
ever they are not recommended for individual clinical
The three-compartment (3C) model expands on the 2C subject evaluations or for examining short-term
model and controls for the variability of one of the changes in body fat (Burden et al., 2005). Anthropo-
FFM components, with the 3C model dividing the metric techniques usually demonstrate the largest
FFM into water and remaining solids (Siri, 1961). standard error and lowest correlation coefficients
Water impacts significantly on the variability of the when compared against other techniques for estimat-
FFM density as it has the lowest density, but comprises ing total-body fat such as DXA, BIA, or in-vivo neutron
the largest mass and volume of the FFM components activation analysis (Eisenmann et al., 2004; Daniel
(Siri, 1961). The 3C model requires that a measure- et al., 2005). These latter techniques are sometimes
ment of densitometry is combined with a measurement referred to as criterion methods or gold standards,
of TBW. As the 3C model is still assuming the protein but care should be taken with this approach as cer-
and mineral content of the FFM is constant, the esti- tainly all of these methods have error that cannot be
mated values for the solids compartment would be discounted.
incorrect in clinical patients with depleted body pro- Indices of weight and height have been developed
tein mass and bone mineral content (BMC). to provide a simple method of body composition. The
majority of studies that define obesity in disease states
rely on the body mass index (BMI), which, as stated
FOUR COMPARTMENT earlier, is weight divided by height squared. Although
this method is widely used and recommended by the
The four-compartment (4C) model breaks the body World Health Organization, it is limited as a measure
into FM, water, mineral, and protein. The 4C model of body composition, as it is not able to quantify FM or
takes into account the individual variability in the com- distinguish between fat and lean tissue, and subjects of
position of the FFM and is considered the best com- the same BMI may differ widely in fatness (Ellis, 2001).
monly available method for measuring body The normal relationship between height and weight is
composition as the more components of FFM that altered in disease states and with the limited sensitivity
can be measured, the better the accuracy. In the 4C of BMI z-scores to predict increased body fat in both a
model, the mineral component can be measured by clinical and a healthy population, BMI is considered a
BMC and protein mass by neutron activation. How- poor measure of body fat in clinical situations (Warner
ever, neutron activation is not widely available, so the et al., 1997; Wells et al., 2002; Eto et al., 2004).
common 4C chemical model measures BMC with dual Circumferences, commonly the mid-arm and waist,
energy X-ray absorptiometry (DXA) and this model are also quick and simple methods that are taken to
assumes that protein mass is proportional to the represent body composition, particularly in low socio-
BMC. This model requires the measurement of body economic countries. Waist-circumference measure-
weight, body volume by densitometry, TBW by deuter- ments can provide a validated measure of visceral
ium dilution, and BMC by DXA. adipose tissue (Janssen et al., 2002; Zhu et al., 2002;
Bosy-Westphal et al., 2006) and mid-arm circumfer- component of the body that contains the energy metab-
ence has been shown to represent malnutrition olising, work performing tissue; for example, the
(Kumar et al., 1996; Powell-Tuck and Hennessy, 2003). muscles and organs (Moore et al., 1963). Body cell
Skinfold-measurements are commonly used because mass measurements by TBK can be used in health
of their low cost, portability, and simplicity. The meas- and disease, because potassium concentrations in
urement of skinfold thickness is taken by grasping the BCM are constant and kept within strict limits by
skin between thumb and forefinger and measuring this homeostatic mechanisms (Edmonds et al., 1975).
thickness with callipers. Duplicate measurements are Unlike other methods, TBK measurements will not be
recommended to improve accuracy and reproducibil- affected by limitations such as cellular fluid shifts, so
ity. A number of measurements at different sites can be changes in TBK will be identifying true changes in
used in age and gender-specific equations to determine BCM and not just reflecting the changes in weight
body composition (Durnin and Womersley, 1974). (Trocki et al., 1998). The other advantages of this
Skinfold-measurements are based upon two assump- method are that it is noninvasive and requires limited
tions; that the thickness of subcutaneous fat represents effort by the subject. The disadvantages of this method
a constant proportion of the total body fat, and that the are that it is not widely available, that equipment is
measurement sites represent the thickness of the total expensive, and that it can be time consuming.
body fat. Neither of these assumptions has been
proven. The high variability of skinfold-measurements
may be due to the callipers used, the technique applied, DENSITOMETRY
the increased error with high fat content, and the
inappropriate application of prediction equations. Air displacement plethysmography (ADP) is a relatively
new method available to measure body composition
and presents a preferred alternative to underwater
WHOLE BODY POTASSIUM COUNTING weighing. The only available system for ADP is the
Bod Pod® (Life Measurements Instruments, Inc., Con-
Whole body counting is the method used to determine cord, CA) (Dempster and Aitkens, 1995) (Figure 7.2).
TBK. Total body potassium is represented by potas- The Bod Pod® system is divided into two chambers, a
sium-40, a naturally occurring radioactive isotope that
emits a gamma ray. Potassium-40 is primarily found
intracellular and not in stored fat. As the subject is
measured by the counter, the gamma rays emitted by
the potassium at 1.46 MeV are detected by sodium
iodide crystals in either single or multidetector config-
urations (Figure 7.1). Depending on the scanning
system, measurements are taken over a few minutes
to an hour.
As 98% of TBK is located in the BCM, whole body
counting of TBK is considered the best body compos-
ition index for identifying the BCM (Pierson and Wang,
1988). Body cell mass is defined as the cellular
7.2. The Bod Pod® (Life Measurements Instruments, Inc., Con-

7.1. Whole body counter. cord, CA) body composition system.
measurement chamber and a reference chamber, with their X-ray attenuation properties. Bone is composed
a computer-operated oscillating diaphragm between of calcium and phosphorus so it has high attenuation,
the chambers. The sinusoidal volume perturbations lean tissues are composed of oxygen and electrolytes
produced by the diaphragm result in small pressure with a medium attenuation and FM is predominately
changes and the ratio of the pressures indicate the hydrogen and carbon with low attenuation properties.
volume of the measurement chamber in adiabatic con- Using a series of assumptions and algorithms, the
dition, using the principle of Poisson’s Law: attenuation for fat, lean, and bone allows the develop-
ment of pixel-by-pixel estimation of body composition.
ðP1 =P2 ¼ ðV2 =V1 Þ Þ:
For a whole body measurement approximately 40% of
The Bod Pod® measurement of body volume firstly pixels are classified as containing bone, the remaining
requires a calibration of the chamber at 0 L, to estab- pixels are used to estimate the body’s lean-to-fat ratio.
lish baseline, and at 50 L. The subject, dressed in min- It is assumed that the lean tissue over bone has the
imal clothing and a hair cap, then sits in the chamber same fat-to-lean ratio as that for nonbone pixels in the
for two 50-second volume measurements. The two same scan region, so this estimated value is applied to
measurements must be within 150 ml or 0.2% of each the lean tissue component in the adjacent bone pixels.
other, whichever is the smallest, with a maximum of Therefore, the lean-to-fat composition of the total lean
three attempts. Thoracic gas volume is then measured tissue mass is based on sampling only one-half of the
within the Bod Pod® or can be estimated. The raw body whole body.
volume given by the Bod Pod® requires adjustment for Although DXA studies are increasing in popularity
the volume of isothermal air found in the lungs and in nutritional studies, such studies should be inter-
near the body surface, as it compresses 40% or more preted with caution because, as previously stated, the
under pressure changes. To correct for the isothermal technique does not represent a reference technique.
air, body volume is adjusted for thoracic gas volume Studies have shown that the bias of DXA is unreliable
and surface area artefact. Once corrected body volume for monitoring body composition longitudinally or in
is known, the principles of densitometry are applied case-controlled studies as results vary with gender,
and body density is calculated from body mass and size, fatness, and disease state (Williams et al., 2005).
volume. Body density can be used to estimate body Issues such as hydration and tissue thickness have also
fat with a 2C body composition model, or be used in been investigated for their effect on DXA measure-
combination with other methods for a 4C body comments (Jebb et al., 1993; Kohrt, 1998). As DXA assumes
position model. that the lean tissue is normally hydrated, the addition
The advantages of the Bod Pod® are that it is quick, of fluid results in an underestimation of FM changes.
simple, and noninvasive. Studies have found that it is a There are also several instrumental factors that
reliable and valid measurement in adults and children may affect DXA measurements of body composition.
(McCrory et al., 1995; Nunez et al., 1999). The limita- Results have been shown to differ with manufacturer,
tions of the Bod Pod® lie with the limitations of densi- software version, and beam mode (Kistorp et al., 2000).
tometry when used as a 2C technique. Assuming the When DXA measurements are performed in the same
density of the FFM is similar in all ages and disease subjects but on different brands of equipment, there
states will lead to overestimation of fatness in condi- has been shown to be significant differences in the
tions where fluid retention and under mineralisation body composition estimates (Tothill et al., 1993). The
decreases the density of the FFM. difference may be due to the differing algorithms used
to divide the soft tissue mass between lean and fat
compartments or the number of pixels assigned as
DUAL ENERGY X-RAY ABSORPTIOMETRY containing bone. Despite the limitations of DXA, the
technology provides a body composition technique
Dual energy X-ray absorptiometry (DXA) was origin- that with some further research will be useful in many
ally designed for measuring the amount of bone min- settings. The measurements are simple, quick and
eral in the body; however, it can also measure FM and painless to perform, give immediate results, require
FFM, and is becoming a favorable body composition minimal radiation dose, and are available in many
assessment technique. A DXA scan requires an X-ray clinical settings.
source to produce a broad photon beam that is filtered,
yielding two different energy peaks. The photons pass
through the body’s tissues and the resulting attenu- HYDROMETRY
ation between the two energy peaks is characteristic
for each tissue. The concept of DXA technology is that Total body water can be measured using the dilution
photon attenuation is a function of tissue composition, principle, which states the volume of the body is equal
with bone, lean tissue, and fat being distinguishable by to the amount of tracer added to the body divided by
Zc
Increasing
Reactance frequency
Phase Z
angle
Resistance R0
7.3. Cole–Cole plot.
the concentration of the tracer in the compartment For whole-body BIA measurements, four electrodes
(Edelman, 1952). The most commonly used tracer in are placed on the wrists and ankles and a tetra polar
this method is deuterium, but may also include triti- arrangement is utilized (Lukaski et al., 1985). Segmen-
ated water or oxygen-18 labeled water. The assump- tal measurements are also possible by altering elec-
tions of the technique are that when the tracer is trode placement to the specific segment required.
ingested, the tracer is distributed equally only in the A current at 50 kHz is passed through one set of elec-
exchangeable pool, the rate of equilibration is rapid, trodes, while the voltage drop is measured, and imped-
and neither the tracer nor body water is metabolized in ance derived, by the other set of electrodes. There are
the equilibration time. two assumptions involved in this measurement to
After providing a predose sample of blood, urine, or determine body volume; the body is a collection of
saliva, the subject drinks a dose of the labeled water. cylinders with their length proportional to their height,
Once the equilibrium time of 4–5 hours has passed, a and the reactance contributing to impedance is small,
postdose sample of bodily fluid is analysed by mass with the resistance considered equivalent to
spectrometry. The sample is corrected for excretion, impedance.
exchange with nonaqueous hydrogen or oxygen, and The standard BIA method uses just one current at
isotope fractionation. From the measurement of TBW, 50 kHz, but multifrequency analysis is also possible. By
FFM can be estimated, which requires an assumed passing currents between 10 kHz and 1 MHz through
value for FFM hydration. The assumed constant is the body it is possible to measure intra and extracellu-
not consistent over age or health status (Fomon et al., lar fluid. At zero frequency the current can not pass
1982; Lohman, 1986). through the cell membrane, so ECF can be determined
With this method, TBW can be measured with an and at infinite frequency both intra and extracellular
accuracy of approximately 1–2%. The advantages of fluid are penetrated so both can be examined. Meas-
isotope dilution are that it is accurate and requires urements are not possible at zero (R0) and infinite
minimal co-operation so it can be used in a range of frequency, so the value at characteristic frequency
ages. However, a disadvantage of this method is that (Zc) is mathematically derived by fitting the shape of
the analysis is time consuming and the entire approach the reactance versus resistance curve (Cole and Cole,
not suitable in abnormal hydration states if body com- 1941) (Figure 7.3).
position is the final outcome required. Considerations for all BIA measurements include
room temperature, body position, lead placement,
prior activity, and food intake. The benefits of this
BIOELECTRICAL IMPEDANCE ANALYSIS method are that it is portable, inexpensive, and simple.
The problem of this method is that the assumptions are
Bioelectrical impedance analysis (BIA) measures the not entirely true, measurement error is likely in sub-
impedance of the body tissues to the flow of a low level jects with altered hydration levels or clinical condi-
alternating current. The principle of BIA is that when a tions, and conversion to FFM is population specific.
current is passed through the body it will only pass
through the water and electrolyte containing tissues
that have low impedance, not the body fat or bone ADDITIONAL METHODS
which have poor conduction properties (Nyboer,
1959; Thomasset, 1962). Therefore as impedance is Several methods which are less commonly used in
proportional to body water, we can determine the body composition research because of the cost and
volume of TBW. availability are computed tomography (CT), magnetic
resonance imaging (MRI), in vivo neutron activation metabolism. An initial attempt to remove the con-
analysis (IVAA), and total body electrical conductivity founding affect of size, shape, and body composition
(TOBEC). Computed tomography and MRI are con- was proposed by Sarrus and Rameaux (1839), as the
sidered the most accurate methods available for quan- surface law, which was thought to enable comparisons
tification of total and regional adipose and skeletal of energy expenditure between different animals.
muscle tissue. Computed tomography uses the rela- This law states that, when expressed relative to
tionship between differences in X-ray attenuation and body surface area, energy expenditure (or metabolic
differences in the physical density of tissues to con- rate as it was termed), was constant in adult home-
struct a two-dimensional image and determine cross- otherms. The surface law became very popular and
sectional area of the fat, bone, muscle, and organs. rapidly became entrenched in physiological doctrine.
Magnetic resonance imaging estimates the volume of The theoretical bases of the law expounded at the time
fat tissue by analysing the absorption and emission of were summarized much later by Kleiber (1947). He
energy in the radio-frequency range of the electromag- stated that the metabolic rate of animals must be pro-
netic spectrum. portional to their body surface area. This statement
In vivo neutron activation analysis is used in body was based upon the following observations:
composition to quantify elements in the body includ-
1. The rate of heat transfer between animal and envir-
ing hydrogen, carbon, nitrogen, oxygen, calcium, and
onment is proportional to the body surface area.
phosphorous. This method uses a neutron field to
2. The intensity of flow of nutrients, in particular
induce a nuclear reaction in the body’s atoms depend-
oxidizable material and oxygen, is a function of
ent on the energy of the neutrons. Total body electrical
the sum of internal surfaces which in turn is pro-
conductivity can be used to measure TBW. This tech-
portional to the body surface.
nique uses coils to generate an electromagnetic field,
3. The rate of supply of oxidizable material and
with an electrical current produced in the conductive
oxygen to the tissues is a function of the mean
tissues of the body and the difference between the coil
intensity of the blood current, which is propor-
impedance when empty and containing a body
tional to the area of the blood vessels, which in
measured.
turn is proportional to the area of the body.
Another new method is the three-dimensional body
4. The composition of the animal is a function of their
scanner which can be used to measure body volume.
body size. The composition may be meant either
The use of a digitized optical method and computer to
anatomically; the larger the animal the lower is the
generate a three-dimensional photonic image of an
ratio of the mass of metabolically active organs to
object was developed in the 1950s and was used as a
the mass of metabolically inert organs; or the com-
technology for whole-body surface anthropometric
position may be meant chemically; the larger the
measurements in humans (Hertzberg et al., 1957).
animal the lower its percentage of “active
The newly developed 3DPS system (Hamamatsu Pho-
protoplasm.”
tonics KK, Hamamatsu, Japan) collects a maximum of
5. The cells of the body have an inherent requirement
2 048 000 data points in 10 s and generates values for
of oxygen consumption per unit weight, which is
total and regional body volumes and dimensions.
smaller the larger the animal.
There is much potential in this new method; however,
complete validation studies are still required. An example of the popularity of this law, at this time,
was that when Mitchell et al. (1940) produced data
from the rat that did not fit the law it was suggested
RELATIONSHIP BETWEEN ENERGY that they had made fundamental errors in their calcu-
METABOLISM, BODY SIZE, AND COMPOSITION lation of body surface area. The possibility that the
Law itself was flawed did not seem an option!
These two biological parameters are intimately Mathematically, bodies of similar shape have sur-
related and it is of extreme importance that the rela- face areas proportional to the squares of their linear
tionship is understood when undertaking studies in dimensions. Similarly, their volumes are proportional
the field. Whilst it is almost self evident that there will to the cubes of their linear dimensions. So if density is
be relationships between FFM and resting metabolic constant then surface area is proportional to two-
rate, for example, unless understood and accounted thirds power of body weight. In this way the surface
for comparisons of energy expenditure between area law came to be interpreted as metabolic rate
species or within species when there are major dis- expressed relative to body weight raised to the two-
crepancies in body size or body composition will be thirds power. This expression of energy expenditure
confounded. relative to body weight was accepted, almost exclu-
This relationship and potential problem was appar- sively, and used throughout human and animal studies
ent to some of the earliest students of energy for 70 years.
The first three decades of the twentieth century saw in three different ways – as lean body mass, FFM, and
the realization that while the surface law might be the cell mass.
most appropriate method of standardising metabolic Owen et al. (1987), determined that resting meta-
rate, surface area itself could not be defined suffi- bolic rate was best predicted in adult men when FFM
ciently well. It was being suggested that another power was included in the regression equations, and others
function of weight be sought that might relate to meta- (Ravussin and Bogardus, 1989) have addressed in
bolic size and in 1932 Kleiber suggested the three- detail the expression of energy expenditure relative to
quarters power as the best function of body weight to FFM. These authors suggest that FFM should be used
standardize metabolic rate in adult homeotherms as the denominator in comparisons of energy expend-
(Kleiber, 1932). iture between individuals. Indeed, they take the con-
Almost immediately Brody and colleagues (Brody cept a step further. They suggest that because of a
and Proctor, 1932; Brody et al., 1932) put forward a mathematical bias it is incorrect to express metabolic
more defined, and somewhat specific, power of 0.734 rate data per kilogram FFM. Also, that regression
based on the analysis of data from a wide range of analysis should be used to take into account the effect
mammals. An official “seal of approval” was given to of FFM upon total energy expenditure. This is a slightly
this power function by the US National Research different approach to using a power function or weight
Council in 1935, although the committee stated that of FFM but nevertheless the same effect is achieved.
whether the change from 0.75 to 0.734 was either bio- Here is the fundamental issue. Whilst it might seem
logically or statistically valid was uncertain. intuitive that dividing energy expenditure by body
Later Kleiber (1932) showed that metabolic rate weight or FFM “adjusts” for body weight or FFM, this
was best expressed to body weight0.75 in a group of is not necessarily the case.
mammals ranging from a mouse to cow, differing in
weight by a factor of almost 30000. Importantly, in this
particular study, the best power was derived statistic- LOG–LOG REGRESSION
ally without recourse to a physiological model.
Interestingly, it has been suggested that elastic cri- Expressing resting metabolic rate (RMR), in this
teria impose limits on biological proportions, and con- example as kcal/kg FFM, is equivalent to the expression
sequently on metabolic rates (McMahon, 1973). This kcal/kg FMM1. The power here of 1, is obviously not the
paper shows elegantly that when one considers funda- power function to effect an appropriate adjustment. It
mental aspects of size and shape it can be shown that might be tempting to try an adjustment such as kcal/kg
maximal power output in animals, at least, is propor- FFM0.75 as suggested by Kleiber (1947) for body weight.
tional to (weight3/8)2 which is equivalent, of course, to However, it is not necessary to guess or assume an
weight0.75. appropriate power function as it can be simply calcu-
Appropriate methods of expressing energy expend- lated using log–log regression. The simplest approach,
iture relative to body weight were still actively being which has an obvious connection with linear regres-
sought more than 20 years later (Sinclair, 1971). The sion, is to consider the correlation between the loga-
surface law was still a consideration although attitudes rithm of the index RMR/FFMPand the logarithm of
towards this model were now less intransigent, as FFM. The log index can be rearranged as follows:
shown by the fact that when the data produced by
log ðRMR=FFMP Þ ¼ log ðRMRÞ p= log ðFFMÞ;
Sinclair for energy expenditure in neonates did not fit
the model, the model was questioned and not, as pre- which shows why logarithms are useful in this case.
viously, the data. They allow the index to be expressed as a linear func-
tion of log (RMR) and log (FFM), which is then suitable
for analysis by linear regression. If the log index is to be
ADJUSTMENT RELATIVE TO BODY uncorrelated with log (FFM) then p must be chosen to
COMPOSITION remove all the log (FFM) information from log (RMR).
This is equivalent to saying that p should be the slope
At the same time that body weight was being adjusted of the regression line relating log (RMR) to log (FFM).
by using a power function, the concept that energy Natural logarithms, to the base e, have some advan-
expenditure was best expressed relative to “active tages over base 10 logarithms.
tissue mass” was being put forward. This concept In reality, the value of p is unlikely to be a simple,
was first voiced by two scientists previously men- round number such as 0.75 say, and the value, like any
tioned, Benedict and Talbot in 1914 (Benedict and other regression coefficient will have a standard error.
Talbot, 1914). The major problem of this method of Thus, often in these circumstances a value of p is
expression, acknowledged by these workers, was that chosen that is numerically convenient and statistically
the calculation of active tissue mass has been defined within the confidence interval for p.
30 This correlation was estimated in nearly every case

25
when energy expenditure was expressed per kg0.5-body
weight. Lawrence (1988) explained this by the fact that
20
BCM (kg)
the percentage differences in body weight when raised

15 to the power 0.5 are virtually the same as the percent-
10 age differences in energy expended during a particular
task if half the total energy is expended in carrying out
5
a fixed amount of external work. Consequently the
0 energy expenditure when expressed per kg0.5 body
1 1.2 1.4 1.6 1.8
weight would be similar between subjects. This explan-
Height (m) ation was offered to account for observations of adult
7.4. Relationship between body cell mass (BCM) and height. Gambian women. Basal metabolic rate has also been
shown to be relatively constant when expressed on a
per kg0.5 body weight basis.
9 One should now pose the question why the weight
8
power is close to 0.5 in humans, appreciably less than
7
BCM/height2.5
6 Kleiber’s power of 0.75 in animals. Put statistically the

5 correlation between body size and energy expenditure
4 across species is very close to 1, whereas in humans it
3 is much lower, about 0.7. For prediction purposes the
2 slope of the regression line is equal to the ratio of the
1
standard deviations of theyandxvariables (i.e., logged
0
1 1.2 1.4 1.6 1.8 energy expenditure and body weight) multiplied by the
Height (m) correlation, r, between them. So if the ratio of the
7.5. Relationship between body cell mass (BCM)/height2.5 and standard deviations is 0.75 (i.e., that proposed by
height. Kleiber) and the correlation is about 0.70, the best
slope for prediction purposes will be close to 0.5.
An example of this approach is shown in Figures Evidence to support the expression of energy
7.4 and 7.5. The first figure shows the relationship expenditure relative to body weight0.5 can also be
between BCM and height in a group of 73 healthy found in the literature relating to animal husbandry.
females between the ages of 6 and 17 years. Clearly Millward and Garlick (1976) suggested that heat pro-
the two are related with a correlation of 0.94. Following duction (energy expenditure) raised to the power 0.56
log–log regression of these data, the value p was deter- might be a general physiological relationship. This
mined to be 2.35 and a statistically valid and more speculation was based upon the findings that total
convenient power of 2.50 was chosen. In Figure 7.5, energy expenditure in growing pigs was best expressed
the relationship shown is that between BCM divided by relative to body weight0.56 (Kielanowski, 1969; Thor-
height raised to the power 2.50. Again clearly there is beck, 1969) and also in rats(Walker and Garret, 1970).
now no relationship and so expressing BCM in this way The same relationship had also been reported in pigs
removes the influence of height. some 30 years previously (Brierem, 1939).
A number of other studies have also found that a Adjusting metabolic variables for differences in body
square root function normalizes or adjusts a number of composition and body size is often necessary. But,
different physiological variables. Total energy expend- inappropriate adjustment can distort the picture and
iture, as measured using the doubly labeled water tech- make interpretation difficult, or worse, lead
nique, was best expressed as kcal/kg body weight0.5 in a to inaccurate conclusions. Whilst the simplicity of
cohort of infants aged between 6 and 26 weeks (Davies dividing metabolic variables by body weight or FFM, is
et al., 1989). This adjustment was also appropriate for appealing, it is clear that in most cases it is inappropriate.
measurements of sleeping metabolic rate in infants at 12
weeks of age. Interestingly the value of 0.5 was statistic-
ally appropriate when sleeping metabolic rate was exp- DISCUSSION POINTS
ressed as kcal/kg body weight0.5 and as kcal/kg FFM0.5.
Further support for using kg0.5 as an adjustment 1. Consider the relative advantages and disadvan-
for body weight has been provided by a study on adult tages of indirect and direct calorimetry to assess
Gambian women (Lawrence, 1988). In this study there energy metabolism, in infants and in children.
was a significant negative correlation between energy 2. How would you design a study to evaluate the
expenditure per kg body weight and body weight ability of a new body composition method to assess
during many activities including sitting and standing. percentage body fat?
3. Describe three circumstances where an inappropri- Brody, S. and Proctor, T. (1932). Growth and development
ate expression of energy expenditure relative to with special reference to domestic animals: further inves-
body composition could lead to inappropriate tigations of surface area in metabolism. University of Mis-
conclusions. souri Agricultural Experiment Station, Research Bulletin,
4. Write a paragraph that explains the doubly labeled 116.
Brody, S., Proctor, T. and Ashworth, J. (1932). Basal metab-
water method that would be suitable for inclusion
olism, endogenous nitrogen, creatinine and neutral sul-
in an information package for parents of children
phur excretions as functions of body weight. University
to be studied.
of Missouri Agricultural Experiment Station, Research Bul-
5. What are the factors that may cause errors in deter- letin, 220.
mining fat free mass (FFM) from bioelectrical Burden, S. T., Stoppard, E., Shaffer, J., et al. (2005). Can we
impedance analysis (BIA)? use mid upper arm anthropometry to detect malnutrition
6. List the disadvantages of a method based on the in medical inpatients? A validation study. Journal of
two-compartment (2C) model of body Human Nutrition and Dietetics, 18, 287–294.
composition? Carpenter, T. and Fox, E. (1923). Alcohol check experiments
7. What adjustments need to be made to body volume with portable respiration apparatus. Boston Medical and
when measuring a child in the Bod Pod®? Surgical Journal, 189, 551–561.
8. Discuss the use of magnetic resonance imaging Cole, K. S. and Cole, R. H. (1941). Dispersion and absorption
(MRI) as a method for determining body in dielectrics. Journal of Chemical Physics, 9, 341–351.
composition. Coward, W. (1988). The doubly-labelled water (H2O)-H-2-O-
18 method–principles and practice. Proceedings of the
Nutrition Society, 47, 209–218.
Coward, W. A., Roberts, S. B. and Cole, T. J. (1988).
Theoretical and Practical Considerations in the Doubly
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8 Evolutionary Endocrinology
Richard G. Bribiescas and Michael P. Muehlenbein
INTRODUCTION of key life history events (Finch and Rose, 1995).

Childhood growth, reproductive maturation, and
Hormones do not fossilize. Yet, arguably, they are as reproductive senescence all result from changes in hor-
important to understanding the evolution of Homo mone production. The significance of some changes,
sapiens and other primates as any fossil specimen. such as the decline in estrogens during menopause,
The role of hormones in understanding human life remains to be fully understood from an adaptive per-
history evolution emerges from how genes translate spective; however, the impact of these changes on
into phenotype with considerable input from environ- reproductive investment is unequivocal. In this chap-
mental cues. Most hormones are evolutionarily quite ter, we present an overview of how hormones contrib-
conservative, with very similar if not identical chemical ute to important life history trade-offs, events, and
structures between species. Many hormones that flow characteristics in humans. In doing so, we introduce
through the veins of humans are identical to those that and describe various hormones that are illustrative of
flow through the most exotic vertebrate. Other hor- human life history evolution. The hormones discussed
mones and receptors, however, can differ in subtle but are not meant to represent an exhaustive list. Only a
important ways between species and even individuals. few representative hormones are discussed to illustrate
Hormonal variation, as reflected by circulating levels as the evolutionary significance of endocrine function in
well as chemical structure, are of central importance to human life histories.
the evolution of human life histories, both from a
macro- and microevolutionary perspective.
The evolutionary significance of hormones is HOW AND WHAT IS MEASURED
clearly evident in the multitude of functions that are MAKES A DIFFERENCE
served, including growth, reproduction, metabolism,
and senescence, all of which are central to the evolu- The amount of hormone that is produced is the most
tion of human life histories. Hormones are inextric- common mode of assessment in contemporary clinical
ably involved in the optimal allocation of time and and biological studies, and for good reason. Hormone
energy. Insulin, leptin, and cortisol, for example, initi- levels provide useful insights into the physiology of an
ate and manage the flow and assessment of energetic organism, such as the presence of illness. For example,
assets such as glucose and fat. Indeed, hormones are Graves’s disease is the overproduction of thyroid hor-
involved in life history trade-offs that influence many mone, resulting in greater than expected metabolic
aspects of human health (Bribiescas and Ellison, rates and unpleasant symptoms such as bulging eyes.
2008). Testosterone, estradiol, and oxytocin affect A low level of insulin is indicative of type II diabetes.
behavioral patterns that result in differences in how Yet, absolute levels only provide a partial picture.
individuals allocate their time, such as in the trade-off Variation in hormone levels can result from three basic
between mate seeking and parenting. In essence, hor- sources; production, clearance, and bioavailability,
mones are a common biological currency that humans usually resulting from carrier protein binding. Produc-
and other primates share with other organisms. This tion is the amount of hormone that is manufactured
allows biological anthropologists to assess the evolu- and secreted into the circulatory system. This is the
tion of life history patterns in reference to a common most common form of variation. However, hormone
physiological aspect, endocrinology (Bribiescas and levels can also be affected by clearance rates, or how
Ellison, 2008). fast the hormone is flushed from the body by the liver
Also important to the evolution of life histories is and kidneys. Finally, bioavailability, or whether the
the contribution of hormones to the onset and timing hormone is capable of activating receptors, can be
127
128 Richard G. Bribiescas and Michael P. Muehlenbein
affected by what proportion of the hormone is bound HORMONE FORM, FUNCTION,

by a carrier protein. For example, the vast proportion AND ASSESSMENT
of sex steroid such as estradiol and testosterone in
circulation is bound to a carrier protein such as sex The standard definition of hormones states that they
hormone binding globulin (SHBG) (Griffin and Ojeda, are chemical substances secreted by glands into the
2004). Sex hormone binding globulin packages the circulatory system, ultimately stimulating receptors
steroid and allows it to be carried freely by the circula- on distant target tissues. This is mostly true although
tory system until it is needed. The mechanism that hormones can also enact local or paracrine actions
frees the steroid from its carrier protein is not com- close to the site of production as well as autocrine
pletely understood, but the amount of carrier protein actions on the originating cells (Griffin and Ojeda,
can affect the availability, activity, and influence of a 2004). Assessment of hormones can be done with a
hormone in the body. For example, increases in SHBG variety of biological substrates and fluids, including
probably account from some of the declines in testos- blood, urine, feces, hair, saliva, cerebral spinal fluid
terone in some older men (Gray et al., 1991). (CSF), and tissue. Each medium provides unique chal-
Sample collection protocols, time of day, and fluid lenges, limitations, and advantages, depending on the
medium also influence subsequent measurements. hormone, the research question, and the species. For
Moreover, the rate and pattern of production can pro- example, blood is the most common diagnostic fluid in
vide important information into endocrine physiology. clinical settings while urine, saliva, and feces are most
For example, many steroid hormones are under the often used in field biology conditions. While blood
control of other hormones that are released in a pulsa- provides access to most hormones, sample collection
tile manner. The frequency and amplitude of secretion is invasive and optimally performed in clinical settings.
can also serve as a window into endocrine function. Saliva is much less invasive but is most appropriate for
Older men for example illustrate changes in pulsatility steroid assessment although progress has been made
in their patterns of luteinizing hormone (LH) and fol- with some protein hormones (Groschl et al., 2001,
licle stimulating hormone (FSH) secretion with age 2005). Urine and feces is often used under conditions
(Takahashi et al., 2007). Luteinizing hormone stimu- in which sample collection is opportunistic and subject
lates the production of testosterone in men and estra- manipulation is not possible, as in the case of wild
diol in women while FSH is involved with gamete nonhuman primate studies (Muehlenbein, 2006).
production in both men and women. Hormones in all When assessing the range of variability and bioactivity
these ways vary between human populations, sexes, of a specific hormone, it is important to be aware of the
and age classes. Through this variation, adaptive plas- limitations and advantages of all of these sources of
ticity is revealed that indicates that environmental and hormone data.
lifestyle factors can alter hormone and receptor struc- Blood is often the most direct method of assessing
ture and function. a hormone. However, blood measurements provide a
While hormones are commonly segregated into dis- snapshot of hormonal status and unless multiple draws
tinct categories, such as those related to growth and are made, pulsatile and diurnal variation cannot be
reproduction, it is important to note that most, if not quantified. Salivary measurements allow for multiple
all hormones, exhibit complex interactions and cross- collections over a relatively brief time period but are
talk that span across most physical functions. Organ- only practical in human populations and occasionally
izational classifications used in this chapter are meant in nonhuman primates (Tiefenbacher et al., 2003).
to serve as guideposts for discussion and may not Moreover, salivary measurements can only observe
necessarily reflect a biological reality in the strict sense. steroids, and to a much more limited extent, some
For example, testosterone and estradiol are commonly peptides. Urine assessments dampen pulsatile variabil-
referred to as “male” and “female” hormones. While it is ity, which can be used advantageously. However,
certainly true that testosterone is often found in greater assessments of urinary hormones still necessitate
quantities in male circulation, testosterone also serves an awareness of diurnal variability (Anestis and
important functions within females despite much lower Bribiescas, 2004).
levels. The same applies to estradiol in males.
This chapter serves to not only provide a brief over-
Steroid hormones
view of hormone physiology, but to also provide con-
textual background on how hormones aid in regulating Steroids are small, lipid-soluble molecules derived
the flow of somatic resources such as fat and glucose from cholesterol (Figure 8.1). Consequently, in their
and therefore act as proximate mechanisms for unbound form, they pass freely through cell mem-
adjusting life history trade-offs. Hormones will also branes and affect genetic expression and transcription
be shown to be central to the evolution and mainten- of various agents. Steroids are ancient molecules that
ance of phenotypic plasticity. are shared in all vertebrates (Norris, 2007). Indeed,
Evolutionary Endocrinology 129
22 24
21 20 26
18 25
23
12
17 H
11 27
19 13
16
9 14
1
2 10 8 15 Cholesterol
3 H H
7
4 5
HO 6
Cholesterol side-chain
cleavage enzyme OH OH
O O O O
3β-HSD 21α- 11β- HO
hydroxylase hydroxylase
Deoxy-
Pregnenolone Pregesterone Corticosterone
O O corticosterone O
HO
17α-hydroxylase
OH OH
O O O O
17α-hydroxy OH 17α-hydroxy OH 11-deoxycortisol OH HO OH
pregesterone progesterone
21α- 11β-
3β-HSD
hydroxylase hydroxylase
Cortisol
HO O O O
17,20 lyase
O O O
3β-HSD Aromatase
Aldosterone
Dehydroepi- Androstene- Estrone
synthase
HO androsterone O dione HO
17β-HSD
OH OH OH
3β-HSD Aromatase
Androstanediol Testosterone Estradiol

HO O HO OH O
H 5α-reductase O OH
OH
Aldosterone
Dihydrotestosterone O
8.1. Steroid hormone synthesis pathways. From GNU Free Documentation License: http://en.wikipedia.
org/wiki/File:Steroidogenesis.svg
steroids and their associated ligands may have been of a specific protein hormone both between individuals
important for the evolution of vertebrate phenotypic and populations is not completely understood and often
complexity and share close similarities to steroids in rare, depending on the type of hormone. Protein struc-
plants and invertebrates, such as phytoestrogens ture variation may reflect microevolutionary processes
(Thornton, 2001). The role of steroids encompasses that may have favored a particular protein hormone
reproductive function, metabolism, and behavior. phenotype or limited its range of variation due to strong
Indeed the brain is rich with steroid receptors. For selection pressure. For example, FSH is highly con-
example, mineralocorticoid and glucocorticoid hor- served and is not known to exhibit any variation that
mones are among the most ancient steroids with a affects hormone levels (Lamminen et al., 2005). How-
deep evolutionary history (Baker et al., 2007). ever variation in upstream regulatory regions of the beta
subunit of FSH (SNP, rs10835638; G/T) has recently
been reported that does affect serum levels (Grigorova
Protein hormones
et al., 2008). Luteinizing hormone on the other hand
The second class of hormones consists of large, water- exhibits a “wild” and “variant” type that is found in
soluble molecules encoded and transcribed from spe- many populations. The “variant” type is less common
cific genes that can exhibit a range of variation in their and is most often exhibited among Australian Abori-
genetic structure and action (Nilsson et al., 1997; ginal groups and may be associated with subfertility
Timossi et al., 2000). Much of the structural variation (Nilsson et al., 1997; Lamminen and Huhtaniemi, 2001).
Also worth mentioning are enzymes that regulate Genetic variation is evident in hormone receptors
synthesis pathways of steroid hormones. While not hor- and is related to detrimental effects on fertility. For
mones themselves, these enzymes control the conver- example, point mutations of FSH receptors found in
sion of cholesterol to a specific steroid, often being Scandinavian populations are associated with subferti-
constrained to produce one specific steroid hormone lity and sometimes infertility in women, although
before continuing on to its final end product (Figure the effects on male fertility appear to be less severe
8.1). One such enzyme is aromatase which converts (Tapanainen et al., 1997, 1998). Luteinizing hormone
testosterone into estradiol. Extreme disruptions of mutations can also detrimentally affect fertility or
enzyme structure results in disorders such as congenital cause early or precocious puberty (Latronico and
adrenal hyperplasia, a condition in which the enzymatic Segaloff, 1999).
pathway to the production of cortisol is disrupted
resulting in the erroneous production of an androgen
with testosterone-like properties of phenotypic mascu- ENERGY MANAGEMENT
linization. Nonpathological variation in enzymatic
structure is evident between human populations. How- Energy is often limited in many organisms and must
ever, further research is necessary to determine the therefore be allocated efficiently between competing
fitness implications of population and individual vari- needs such as growth, maintenance, and reproduction
ation (Miller, 2002; Jasienska et al., 2006). (Stearns, 1992; Ellison, 2003). Hormones are intri-
Another set of proteins act as carrier agents for cately involved in the regulation of energetic resources.
hormones, allowing for efficient dispersal away from They both sense and reflect the availability of energy
the site of production. Structural variations in trans- substrates such as glucose and fat, regulating the flow
porter or binding proteins have become more evident. of energetic assets between the needs of growth, main-
Variation in thyroid transporting proteins as well as tenance, and reproduction. The following descriptions
SHBG, for example, have illustrated the potential are not meant to be an all encompassing list, but rather
importance of these agents in hormone activity (van a brief overview of the major hormone functions that
der Deure et al., 2007; Riancho et al., 2008). As an have received significant attention from human evolu-
example, the Asp327Asn polymorphism contributes to tionary biologists.
higher SHBG and testosterone levels among young,
middle-aged, and older men (Vanbillemont et al.,
Growth and organization
2009). Similarly, SHBG polymorphisms were associ-
ated with serum levels in women with the AA genotype Growth is the embodiment of harvested energy from
at the rs1799941 locus exhibiting the highest SHBG the environment. The amount of energy necessary to
levels (Riancho et al., 2008). It is unclear how significant create tissue is a function of the amount of mass and
these polymorphisms are to contributing to between the rate at which that mass is created. From these two
individual variation in binding protein levels; however, processes, we can define the size of an organism and
their potential effects have yet to be fully explored. the pattern in which that tissue is created, otherwise
known as growth rate. Other important factors include
the rate of energetic usage by tissue or basal metabolic
Hormone receptors
rate and the type of tissue being formed and supported.
Both steroid and protein hormones enact their influ- For example, muscle and brain tissue are much more
ence by binding to specific proteins on target cells. metabolically taxing than adipose tissue. Hormones
Indeed the evolution of receptors appears to have been are instrumental for these processes as they influence
a crucial aspect in the emergence of multicellular cellular replication, differentiation, and enlargement
organisms (Whitfield et al., 1999). As with protein hor- as well as the amount of energy to be allocated. For
mones, receptors are genetically encoded and subject more complete discussions of variability in human
to structural variation. Receptors are found on the growth and the evolution of rates and patterns of
surface and within target cells. The density, specificity, human growth, see Chapters 22 and 23 of this volume.
and binding capacity of receptors vary depending on Excellent reviews of the endocrinology of growth and
the type of tissue, the hormone, genetic variation, and development are provided by Cohen and Rosenfeld
hormonal milleau. For example, exposure to high (2004), Grumbach and Styne (1998), and Reiter and
levels of leptin, a hormone that is secreted by fat cells, Rosenfeld (1998).
results in an increase in receptor resistance (Sahu, Within the human lifecycle, the impacts of hor-
2003). Such variation may reflect an important aspect mones on growth and development begin in utero.
of molecular phenotypic plasticity in which hormone Glucose and subsequent increases in insulin, growth
influence is regulated within the context of environ- hormone (GH), and insulin-like growth factor (IGF)
mental conditions. are crucial for overall skeletal growth and fat
deposition. Müllerian-inhibiting factor, testosterone, feedback effect of circulating sex steroids, thus
and dihydrotestosterone promote sex-specific defemi- contributing to the subsequent pubertal growth spurt
nization and masculinization of the genitalia in male (Havelock et al., 2004; Campbell, 2006).
and female fetuses (Grumbach and Conte, 1998). Cir- Comparative studies show that chimpanzees also
culating gonadotropin (LH and FSH) levels in the fetus exhibit adrenarche while other primates do not
peak in the second trimester of development, corres- (Nadler et al., 1984; Muehlenbein et al., 2001). Genetic
ponding with maximal follicle development in females sequence comparisons between humans, chimpanzees,
(Faiman et al., 1976). In males, testosterone levels rise rhesus macaques, and baboons of the enzyme P450c17,
during mid-gestation and then fall prior to birth which is responsible for the conversion of pregneno-
(Siiteri and Wilson, 1974). Testosterone levels in males lone to DHEA, revealed different patterns of DHEA
are also likely responsible for differences in energetic production with very little genetic variation in the
demands on the mother as well as muscle and fat P450c17 gene, illustrating the potentially conservative
deposition compared to female fetuses (Tamimi et al., evolutionary nature of adrenarche coupled with com-
2003). Interestingly, it is becoming increasingly evident plex endocrine regulatory mechanisms that await fur-
that energetic status can alter hormonal milieu in utero ther description (Arlt et al., 2002).
and potentially influence energetic management or During childhood, energy is devoted to increasing
even disease during adulthood (Kuzawa and Adair, tissue investment that will increase survivorship.
2003; Kuzawa, 2005; Barker et al., 2008). During human evolution, this was made possible only
Parturition is accompanied by decreased estrogen through parental or allocare since child foraging
and progesterone and increased gonadotropin levels in returns tend to be quite low (Hill and Hurtado, 1996;
infants that persist for the first few months after birth. Hewlett and Lamb, 2005). Growth rates decline rapidly
Fetal thyroid hormone levels also surge at birth, which during infancy but remain positive and steady
may facilitate new thermoregulatory requirements. In throughout childhood until the early stages of puberty
male infants, there is a second rise in testosterone level when rates of growth of both bone and sexually
that falls again prior to the first year of age (Forest dimorphic tissue rise in dramatic fashion.
et al., 1974). Like the neonatal surge, the functions of At puberty, the hypothalamus becomes much less
temporary elevations in androgen levels (beyond mas- sensitive to circulating steroid levels (Plant et al., 1989;
culinization of genitalia) are incompletely understood, Ojeda, 2004b) and begins producing more gonadotro-
although they may play important roles in sexual dif- pin-releasing hormone (GnRH) in short pulsatile
ferentiation of the central nervous system (Wilson, bursts (usually sleep-related) from the arcuate nucleus
1982) as well as priming of androgen target tissues of the medial basal hypothalamus (King et al., 1985;
(De Moor et al., 1973; Davies and Norman, 2002). Wu et al., 1996). Luteinizing hormone and FSH are
Nutritional factors in addition to injury and illness then released in a pulsatile manner from the anterior
(i.e., immune activation) during development may also pituitary. Leptin, a lipostatic hormone produced by
play important roles in “programming” baseline testos- adipose tissue, in conjunction with other growth
terone secretion for later adulthood (Bribiescas, 2001; factors, could also contribute to hypothalamic matur-
Muehlenbein, 2008). Hormonal priming is discussed in ation (Yu et al., 1997).
more detail in Chapter 21 of this volume. The frequency and amplitude of gonadotropin
Childhood growth is marked by a steady increase in pulses increase throughout sexual maturation, causing
body mass, particularly from bone growth. The hypo- enhanced steroid secretion from the gonads (see
thalamic-pituitary axis is very sensitive to low levels of Grumbach and Styne, 1998 for review). Androgens
steroids and thus keeps gonadotropin levels low (particularly the conversion of testosterone to dihydro-
throughout childhood (Kaplan et al., 1976; Grumbach testosterone) control hair, vocal cord and genitalia
and Styne, 1998). Adrenarche, around six to eight years development, fat catabolism, and skeletal muscle anab-
of age, marks the onset of adrenal androgen secretion, olism in boys. Estrogens from the ovaries control
specifically androstenedione, dehydroepiandrosterone. bi-iliac growth, breast development, and fat redistribu-
and dehydroepiandrosterone sulfate (DHEAS) follow- tion in girls, and androgens from the adrenal cortex
ing stimulation by adrenocorticotropin hormone and ovaries control growth of pubic and axillary hair
(Odell and Parker, 1985; Parker and Rainey, 2004). (Grumbach and Styne, 1998). Interestingly, hormones
Although the roles of adrenal androgens in the onset associated with adiposity, such as leptin, exhibit
of puberty are unknown (Parker, 1991), it has been inverse responses to puberty in males and females,
suggested that DHEAS produced during adrenarche with leptin increasing in females and declining in
may play an important role in human brain matur- males (Garcia-Mayor et al., 1997). Within the context
ation, and thus cognitive development (Campbell, of other mammals, this may indicate differential
2006). These androgens may also be involved with investment in reproductive effort, with adiposity
decreasing hypothalamic sensitivity to the negative being important to childbearing and survivorship
while muscle growth provides males with competitive reproductive function are provided by Baird (1984),
advantages (Bribiescas, 2001, 2006a). Carr (1998), Carr and Rehman (2004), Casey and
As is evident, a number of hormones are respon- MacDonald (1998), Knobil et al. (1988), Ojeda
sible for growth and differentiation. Growth hormone (2004b), and Wood (1994).
(GH) is released in a pulsatile pattern from the anterior Similar to the neuroendocrine control found in
pituitary gland following stimulation by growth hor- human males, GnRH is released in short pulsatile
mone-releasing hormone from the hypothalamus bursts from the arcuate nucleus (“pulse generator”) of
as well as thyroid hormones (Reiter and Rosenfeld, the medial basal hypothalamus (Reichlin, 1998).
1998). Somatostatin (somatotropin release-inhibiting Gonadotropin-releasing hormone stimulates LH and
factor) inhibits the release of GH. Growth hormone FSH release from the gonadotrophs of the anterior
stimulates tissue and skeletal growth primarily by pituitary gland (adenohypophysis) (Ojeda, 2004a).
increasing insulin-like growth factors (IGFs) I and II Thecal interstitial cells of a woman’s follicles secrete
and their variants (IGFs, somatomedins), particularly androgens in response to LH (McNatty et al., 1979).
in the liver and bone (Reiter and Rosenfeld, 1998; Granulosa cells of the ovaries support follicular devel-
Cohen and Rosenfeld, 2004). Gonadal steroids also opment in response to FSH, as well as convert andro-
trigger GH and IGF synthesis and secretion (Attie gens to estrogens (McNatty et al., 1979). Some
et al., 1990; Rogol, 1994). The IGF-binding proteins androgens are produced from the adrenal glands, and
play a number of important roles, including inhibition most of these androgens are aromatized into estrogens
of IGF actions (Reiter and Rosenfeld, 1998). in adipose tissue (Carr, 1998). The major estrogens
Androgens are largely responsible for muscle include estradiol-17b, estrone, and estriol. Estrogens
growth (Herbst and Bhasin, 2004) and development are largely responsible for the development of female
of the hematopoietic system (Jepson et al., 1973). secondary sexual characteristics, endometrial growth,
Glucocorticoids increase circulating glucose, fatty and ductal development in the breast (Wood, 1994;
acids, and amino acid levels (Parker and Rainey, Carr and Rehman, 2004; Ojeda, 2004b).
2004). Cortisol is also important for lung and intestinal The ovulatory (menstrual) cycle of a woman is
maturation (Ballard, 1979). Other hormones that regu- approximately 28 days long, and divided into four dis-
late metabolism, like insulin, glucagon, leptin, and tinct phases: menstruation, follicular phase, ovulation,
ghrelin (Miers and Barrett, 1998; Dobbins et al., 2004; and luteal phase. In the follicular phase, a dominant
Klok et al., 2007), will also play important indirect roles follicle develops and inhibits the development of adja-
in growth and development. cent follicles (Zeleznik, 2004). Luteinizing hormone,
Estrogens (particularly the aromatization of testos- estradiol, and progesterone levels rise throughout this
terone to estradiol in boys) are important for skeletal proliferation phase of the endometrium (Wood, 1994;
development, including epiphyseal fusion (Matkovic, Carr, 1998). Just prior to ovulation, estradiol, proges-
1996; Juul, 2001). Thyroid hormones (T3, triiodothyro- terone, prostaglandin, LH, and FSH levels surge
nine; T4, thyroxine) stimulate protein synthesis and followed by release of the ovum from the follicle.
lipolysis and are important for tissue development Following ovulation (which takes place usually around
(Steinacker et al., 2005). Thyroid hormones are also day 14), the luteal phase begins with formation of the
important for epiphyseal growth (Shao et al., 2006), corpus luteum from follicular cells, and is accompan-
and skeletal tissue modeling and remodeling are largely ied by a drop in estradiol and gonadotropin levels
under the control of parathyroid hormone which alters (Wood, 1994; Carr, 1998). The corpus luteum produces
calcium homeostasis (Hruska et al., 1991; Griffin, large amounts of progesterone in response to estradiol
2004b). Vitamin D increases calcium absorption, and in order to support zygote implantation and mainten-
estradiol improves calcium retention and prevents ance of the endometrium and myometrium, mucosal
bone resorption (Kenny and Raisz, 2002; Heller, development, and glandular development in the breast
2004). Additional growth-regulating peptides include, (Carr, 1998; Casey and MacDonald, 1998). Estradiol
among others, the fibroblast and epidermal growth reaches a secondary peak in the mid-luteal phase, cor-
factors (Reiter and Rosenfeld, 1998; Cohen and responding with a rise in basal body temperature.
Rosenfeld, 2004). Secondary (nondominant follicles) undergo atresia
and apoptosis due primarily to activation of proapop-
totic factors and reduced estrogen, FSH, and proges-
Female reproductive endocrinology
terone levels and increased androgen and prolactin
Female reproductive functions are also under complex levels in the follicular fluid (Rolaki et al., 2005; Craig
control by the endocrine system. For more detailed et al., 2007). Luteolysis, or degeneration of the corpus
discussion of ovarian function, pregnancy, lactation, luteum, takes place in the absence of fertilization with
and menopause, see Chapters 19 and 20 of this volume. subsequent declines in progesterone and estradiol and
Excellent reviews of the endocrinology of female increase in prostaglandin levels (Niswender et al.,
2000). Vascular changes and menstruation ensue. and delivery to the infant. Suckling stimuli from the
A decrease in inhibin B (which normally inhibits FSH infant maintain elevated levels of prolactin and oxytocin
release from the anterior pituitary) and a rise in FSH as well as trigger release of b-endorphin. Prolactin
levels initiate follicular development for the next cycle acts directly on the ovaries to produce a contraceptive
(Groome et al., 1996). effect (McNeilly et al., 1982), and b-endorphin sup-
In the event of fertilization, human chorionic gona- presses pulsatile GnRH release from the hypothalamus
dotropin (hCG) is released by the invading embryo (Franceschini et al., 1989). The combined effects con-
(and later by the placenta) in order to maintain the tribute to lactational infecundability, although maternal
corpus luteum, ensuring continued progesterone energetic status can attenuate lactational amenorrhea.
secretion as well as fetal gonadal development (Licht For example, Toba women of Argentina resume men-
et al., 2001). The placenta also releases estriol in large strual cycling in response to rising C-peptide (insulin)
quantities that stimulate development of the myome- levels despite intense nursing (Ellison and Valeggia,
trium (Conley and Mason, 1990). Progesterone is 2003).
released from the placenta, inhibiting smooth muscle Cyclic ovarian function and menstruation cease in
contraction of the uterine myometrium by inhibiting menopause due to a loss of follicles (for review, see
prostaglandin formation (Sfakianaki and Norwitz, Sievert, 2006). Responsiveness of the ovaries to gona-
2006). Progesterone also likely inhibits maternal dotropins decreases with elevated levels of LH and FSH
immune reactions against the fetus (Thongngarm accompanied by low levels of estradiol, androgens,
et al., 2003). The placenta, ovaries, and corpus luteum inhibin B, and progesterone (Sherman et al., 1976;
all produce relaxin which induces cervical remodeling Metcalf et al., 1982). Dysregulation of endocrine activ-
to accommodate the pregnancy and later parturition ity can further produce vascular dilation which may
(Sherwood, 2004). lead to “hot flashes” (Meldrum, 1983).
Prolactin (PRL) from the anterior pituitary gland
and human placental lactogen (hPL, chorionic soma-
Male reproductive endocrinology
tomammotropin) from the placenta further develop
the duct system and tissue of the mammary gland More specific aspects of male reproductive endocrin-
and stimulate milk synthesis (Neville et al., 2002). ology are covered in greater detail in Chapter 21 of this
Human placental lactogen is also involved in maternal volume. However, a brief summary is presented within
metabolic changes such as elevated glucose levels and the context of how human male reproductive endocrin-
increased insulin resistance which may lead to gesta- ology has been shaped by natural selection and ener-
tional diabetes (Grumbach et al., 1968). Other factors getic constraints. Male hormones such as testosterone
of fetal/placental origin (particularly inhibin A) may be have both organizational and activational effects on
responsible for maternal vascular changes, including males (Griffin, 2004a). In utero, testosterone and other
pre-eclampsia (Rodgers et al., 1988; Bersinger et al., hormones are responsible for internal and external
2002). Such fetal manipulation of maternal resources genital development and organization as well as differ-
may be viewed as the outcome parent–offspring con- ences in somatic composition and brain development
flict in which the genetic interests of offspring and (Grumbach and Conte, 1998; Tamimi et al., 2003;
mothers are not identical (Trivers, 1974; Haig, 1993). Knickmeyer and Baron-Cohen, 2006). After a period
At parturition, maternal corticotrophin releasing of childhood quiescence, hypothalamic sensitivity to
hormone (CRH) levels increase dramatically, possibly circulating testosterone dampens, allowing circulating
under direct fetal control (McLean and Smith, 2001; levels to rise and promote the onset of puberty. During
Snegovskikh et al., 2006). Corticotrophin releasing hor- adulthood, downstream effects of GnRH and gonado-
mone stimulates prostaglandin production which initi- tropins stimulate the production of sperm and sex hor-
ates labor. Androgens produced by the fetal adrenals mones, specifically testosterone and, to a lesser extent,
are converted into estrogens, and a high ratio of estro- estradiol. Follicle stimulating hormone promotes
gens to progesterone likely contributes to the onset of spermatogenesis while inhibin exerts negative feed-
labor and delivery (Challis et al., 2000). Oxytocin rises back on FSH. Luteinizing hormone induces the pro-
both before and after parturition, with the former duction of testosterone and, to a lesser extent,
stimulating muscle contractions associated with labor, estradiol. This system is common among most verte-
and the later stimulating uterine blood vessel coagula- brates and thus reflects common comparative selective
tion following expulsion of the placenta (Wood, 1994; pressures shared by humans (Norris, 2007).
Blanks and Thornton, 2003). As with other mammals, the primary factors
Prolactin is necessary for milk production, and affecting the evolution of male fitness and reproductive
dopamine acts antagonistically to this purpose endocrinology is access to females as well as paternity
(Buhimschi, 2004). Oxytocin, released from the poster- uncertainty (Bribiescas, 2001). It is therefore not sur-
ior pituitary gland, is responsible for milk ejection prising that with the low metabolic costs associated
with spermatogenesis, FSH in males is relatively Variation in insulin sensitivity between human
insensitive to energetic stresses (Klibanski et al., 1981; populations is widely reported, especially among com-
Bergendahl and Huhtaniemi, 1993). Moreover, vari- munities that exhibit unusually high rates of diabetes
ation in FSH levels within the common range of and obesity, such as Pima Amerindians and Samoans
variation is not associated with differences in spermato- (Zimmet et al., 1996; Hanson et al., 2001). Insulin
genesis. Indeed, spermatogenesis is tolerant of a broad resistance was initially suggested to underlie high rates
range of FSH exposure (Kumar et al., 1997; Tapanainen of diabetes in these populations, perhaps as the result
et al., 1997). Coupled with the modest association of of selection for greater efficiency for fat deposition,
spermatogenesis with variation in male fertility (Guzick otherwise known as the “thrifty gene hypothesis”
et al., 2001), it is therefore not surprising that hormonal (TGH) (Neel, 1962). Although recent refinements of
responses to energetic stressors are modest. the TGH more readily support the notion that high
As with most other organisms with internal fertil- rates of obesity and diabetes are the result of contem-
ization, high investment in mate access (libido) and porary changes in diet in high-risk populations,
tissue that augments competition and female attract- specifically significant increases in carbohydrate con-
iveness is supported by male hormones. Absence or sumption (Neel, 1999). More recently, evidence has
severe suppression of testosterone in particular, can accumulated for transgenerational effects in which
dampen libido and somatic investment (Sinha-Hikim maternal condition exerts downstream effects on off-
et al., 2002; Gray et al., 2005). However, human males spring diabetes risk (Gluckman and Hanson, 2004).
exhibit a broad range of variation between individuals Insulin also acts as an important ergostat to the
and populations that is poorly understood. Between- hypothalamus and reproductive system. The hypothal-
population variation may involve an adaptive response amus maintains a significant number of insulin recep-
to minimize the metabolic costs of testosterone- tors, with potent downstream effects on reproductive
induced anabolism in the face of chronic caloric defi- function (Bruning et al., 2000). For example, increases
ciencies (Bribiescas, 1996, 2001) and/or pathogen in urinary C-peptide is associated with the resumption
stress (Muehlenbein, 2008). Maintaining low testoster- of ovarian activity and the cessation of postpartum
one levels in resource-limited and/or high pathogen-risk lactational amenorrhea, suggesting that insulin is an
environments may avoid some immunosuppression active agent in shifting energetic investment between
and suspend energetically expensive anabolic func- present and future reproductive effort in women
tions. Augmenting testosterone levels in the presence (Ellison and Valeggia, 2003).
of fertile and receptive mates, areas of high food
resource availability, and low disease risk habitats will
Thyroid hormones and metabolic regulation
function to maximize lifetime reproductive success
(Muehlenbein, 2008). Between-individual variation in Thyroid hormones, thyroxine (T4) and triiodothyro-
testosterone level is also sensitive to a variety of nine (T3), are produced and secreted by the thyroid
factors, including marital status, fatherhood, and age. gland which is situated around the trachea. Synthe-
Married and pair-bonded men as well as fathers exhibit sized in association with iodine and the amino acid
lower testosterone, perhaps as an indication of greater tyrosine, thyroid hormones are potent regulators of
offspring and mate investment, at the expense of mate basal metabolic rate (Kronenberg and Williams,
seeking (see Chapter 16 of this volume). 2008). Although most thyroid hormone consists of T4,
T3 has a greater affinity for target receptors. Thyroxine
is commonly converted to T3 within target cells. The
Insulin and energy sequestration
production of thyroid hormones are controlled by thy-
Insulin is a protein hormone that is secreted tonically roid stimulating hormone (TSH) which is secreted by
from the pancreas. It is a member of a class of hor- the pituitary gland, which in turn is stimulated by
mones that stimulate growth and regulate cellular glu- thyroid releasing hormone (TRH) from the hypothal-
cose uptake (Nussey and Whitehead, 2001). In essence, amus. Thyroid binding globulin (TBG) binds to T3 and
insulin is an energy sequestering hormone, mopping T4 and acts as a carrier protein in circulation.
up glucose in circulation and making it available for The lack of thyroid hormones, or hypothyroidism,
cellular needs. A lack of insulin results in type II dia- results in weight gain and sluggishness. Hypothyroid-
betes, while insensitivity to insulin reflects the type ism during infancy can cause cretinism, leading to
I form. Insulin is most often measured in blood; how- stunted physical and mental development. Hyperthy-
ever, its metabolite, C-peptide, is readily measured in roidism or excess thyroid hormone, also known as
blood and urine, making it a useful proxy for insulin Graves’s disease, results in accelerated basal metabolic
assessment under remote field conditions in humans rate, weight loss, hyperactivity, and other symptoms
and nonhuman primates (Meistas et al., 1981; Sherry such as bulging eyes (Kronenberg and Williams, 2008).
and Ellison, 2007). Because thyroid hormone synthesis relies on the
availability of iodine in circulation, iodine deficiencies Variation in leptin structure and function between
can result in goiter, an enlargement of the thyroid species is considerable. Comparative investigations
gland which is common in many developing countries have suggested interesting differences between
(Andersson et al., 2005). This enlargement, while human and nonhuman leptin despite its relatively
potentially disfiguring, results from an adaptive conservative chemical structure (Muehlenbein et al.,
response to increase the iodine absorption ability of 2003b, 2005). Among chimpanzees, very little is
the thyroid gland. known although preliminary investigations have
Some variation in thyroid hormone physiology shown that leptin levels are higher in females, per-
within and between human populations is evident, haps reflecting the greater metabolic costs of repro-
although in most cases, the adaptive significance duction (Anestis and Bribiescas, 2007). However no
remains unclear (Aoki et al., 2007). Exceptions are associations between leptin and body mass in male
indigenous circumpolar groups who tend to have captive chimpanzees are evident, perhaps illustrating
higher basal metabolic rates, higher annual levels of the marginal role of adipose tissue modulation in
T4, and augmented winter increases in T4, presumably energy maintenance in this species (Anestis and
as an adaptive response to cold (Tkachev et al., 1991; Bribiescas, 2007).
Leonard et al., 1999, 2002). In addition to interspecies variation, between
population contrasts in leptin function and associ-
ations with body composition are significant. Leptin
Leptin and fat
is lower in males among the Aché of Paraguay even
Per unit mass, fat is the most efficient mode of somatic after controlling for adiposity. However, as a popula-
energy storage. Indeed, adiposity is crucial for surviv- tion, leptin levels are extremely low despite relatively
ing food deficiencies and other sources of energetic high fat percentages. Aché women with 33% body fat
depletion such as disease or infection. It would on average, exhibit leptin levels that are indistin-
therefore be vitally important to evolve a chemical guishable from American anorectic women (7% body
signal that would alert the brain, particularly the fat) (Bribiescas, 2005). Similarly, leptin is a poor
hypothalamus, to fat availability and storage status. reflector of adiposity in Aché men, in contrast to the
Leptin exhibits qualities for such a signal. Leptin is a tight association between leptin and adiposity on
polypeptide hormone that is secreted primarily by fat lean American men (Bribiescas and Hickey, 2006).
cells (adipocytes) (Casanueva and Dieguez, 1999), While polymorphisms in the leptin molecule and
although other secondary sources have been identified. receptor that may influence sensitivity are possible,
Leptin is most commonly measured in blood although it is also possible that lifetime energetic conditions
salivary and urinary assessments have met with limited can influence adult leptin independent of adiposity
success (Groschl et al., 2001; Zaman et al., 2003). In although additional data is needed to test this
essence, leptin often serves as a lipostat, signaling fat hypothesis.
availability to receptors within the hypothalamus and
other regions. The lack of leptin or receptor insensitiv-
Ghrelin and hunger
ity usually causes hyperphagia and extreme weight
gain, most likely due to the brain’s perception that the A recently discovered polypeptide hormone that is
body is experiencing starvation and the lack of adipos- secreted primarily within the stomach, ghrelin levels
ity. Because leptin seems to be a mechanism of ener- are positively associated with hunger and are a potent
getic accounting, the life history implications of stimulant of GH secretion. Ghrelin is found in two
the discovery of leptin are potentially profound forms, total and active. The active or acylated form,
(Niewiarowski et al., 2000), although the functional differs from total ghrelin in that active maintains an
complexity of this hormone has only recently begun N-octanoyl group at the Ser3 position that is believed to
to be appreciated. be necessary for bioactivity (Kojima and Kangawa,
Other proposed functions include influences on 2005). Assessment of ghrelin is limited to blood samples
immune function, growth, and reproduction. For although salivary measurements have been reported
example, leptin modulates T-cell mediated immunity (Groschl et al., 2005).
and reverses starvation-induced immunosuppression Ghrelin is a potentially significant mechanistic agent
in mice (Lord et al., 1998). Leptin administration also of regulating energy intake through its effect on hunger
accelerates sexual maturation in mice although results and satiation. It also plays a significant role in stimulat-
in other mammals such as humans have been equivo- ing the production of GH (Kojima and Kangawa, 2005).
cal (Himms-Hagen, 1999). Here again, as a modulator The seemingly contradictory relationship between
of immunocompetence, leptin appears to be an import- hunger-stimulated increases in ghrelin and its GH
ant mechanism in energy allocation towards infectious stimulating effects remain to be elucidated. Very little
challenges. is known about population variation within humans
but available evidence suggests modest functional far beyond our current realm of understanding,
variation (Chanoine et al., 2003; Shukla et al., 2005; although the underlying strategic behavioral ecology
Bribiescas et al., 2008). aspects have been discussed widely (Cronk, 1991).
However, it is evident that neuroendocrine aspects of
some time-budgeting decisions have intricate relation-
Cortisol and stress
ships with daily activity. For example, among wild
One of the most well known and researched hormones, chimpanzees, individuals tend to engage in hunting
cortisol belongs to a class of steroids known as glucocor- when there is high fruit availability (Watts and Mitani,
ticoids. Cortisol is secreted by the adrenal gland in 2002). The underlying hormonal process likely involves
response to the pituitary hormone adrenocorticotropin greater glucose and insulin levels that allow the high
hormone (ACTH), which in turn results from the hypo- energetic output necessary for a successful hunt
thalamic hormone, corticotropic releasing factor (CRF) (Sherry and Ellison, 2007). Low energy status stimu-
(Kronenberg and Williams 2008). Cortisol is commonly lates increases in ghrelin-induced hunger, thereby
referred to as the “stress” hormone due to elevations that compelling individuals to pursue food acquisition.
occur in response to physical or mental discomfort, or Low energy status can also induce hypoinsulinemia,
even the anticipation of potential discomfort. However, lethargy, and the desire to spend time resting (Elia
the central function of cortisol is to mobilize energy et al., 1984; Jenike, 1996).
resources such as glucose and amino acids through The decision to budget time between present and
muscle breakdown or “catabolism.” Cortisol also acts future reproductive effort, as in the case of parenting
as a potent anti-inflammatory agent. Related steroids versus mate seeking, is a particularly important facet
such as cortisone are commonly used for the treatment of daily life. Such decisions and the effects of hormonal
of inflammation (Kronenberg and Williams, 2008). variation are clearly evident in nonhuman seasonally
The evolutionary function of cortisol appears to be breeding organisms and, in more subtle ways, humans.
to make glucose available for immediate use in times of Because of the high variance in potential fitness in
acute need. As an anti-inflammatory agent, it also acts association with mate availability among males, it is
to postpone attention towards injury and insult in the not surprising that shifts in testosterone are evident in
face of more immediate needs. In the absence of a males investing in reproductive effort compared to
stressor, cortisol commonly exhibits a strong diurnal parenting. Human males who are pair bonded or are
signal with levels being higher in the morning and fathers exhibit lower testosterone levels compared to
declining into the evening (Rose et al., 1972; Knutsson single men as well as those without children (Gray
et al., 1997). Chronically elevated cortisol levels can et al., 2002; Burnham et al., 2003; Gray, 2003). The
result in long-term damage to many tissues, including physiological effects of testosterone variation in asso-
the brain. For example, high glucocorticoid levels can ciation with parenting and pair bonding are unclear,
induce severe damage to the hippocampus, an import- although adaptive alterations of behavior, metabolism,
ant brain region for memory consolidation (Sapolsky or immunocompetence are possible (Mazur and
et al., 1990). A much more detailed discussion of corti- Michalek, 1998; Bribiescas, 2001; Muehlenbein and
sol and stress physiology can be found in Chapter 24 of Bribiescas, 2005).
this volume. In females, the amount of invested time spent in
breast-feeding is contingent on the energetic status of
the mother. Postpartum amenorrhea is a function of
TIME MANAGEMENT nursing frequency and intensity as well as maternal
circulating glucose levels and body mass. Among Toba
In contrast to energy, organisms cannot harvest time. women of Argentina, postpartum amenorrhea is quite
The amount of time an organism has to conduct its short despite heavy nursing investment. With increases
daily tasks of feeding, resting, and reproducing is in body mass and insulin (as reflected by urinary
limited by the number hours in a day. One cannot be C-peptide levels), ovarian function resumes and allows
in two places at once. On a grander scale, organisms women to begin investment in future reproduction
have a finite lifetime to grow and reproduce. Even if an (Ellison and Valeggia, 2003; Valeggia and Ellison, 2004).
individual is able to diminish extrinsic mortality, it is
limited by the species-specific rate of senescence (Hill
Senescence
et al., 2001).
Daily activity budgets during human evolution There are very few hormonal markers of overall senes-
were dictated largely by foraging strategies and effi- cence. No single hormone is responsible for somatic
ciency. The physiological mechanisms that influence degeneration. The most salient hormonal markers of
these daily time budgeting decisions involve intricate senescence are DHEA and DHEAS. Both rise during
neural activity that is obviously extremely complex and adolescence and drop steadily with age (Perrini et al.,
2005). This decline seems to be shared with other that adjust the range and sensitivity of plastic traits?
primates and is therefore evolutionarily conservative Hormones are central mechanisms of phenotypic plas-
(Muehlenbein et al., 2003a; Perret and Aujard, 2005). ticity and modulate gene and phenotypic expression in
While the association with aging is well established, response to environmental cues (Ketterson and Nolan,
the physiological significance of DHEA and DHEAS 1992; Zera and Harshman, 2001).
changes with age remains elusive (Johnson et al., 2002). If phenotypic plasticity is so advantageous, why
Senescence involves intrinsic physiological con- have not organisms evolved the ability to maintain
straints on life span that are inherent to a particular total malleability? In addition to the constraints of
species. While it is not uncommon for humans (even physics (Pennycuick, 1992), there are costs associated
hunter-gatherers) to live well into their 60s and with phenotypic plasticity such the energetic costs of
beyond, the doubling rate of mortality begins to maintaining the physiological capacity to alter
shorten dramatically around the age of 60 (Hill and phenotypes, as well as the potential of misinterpret-
Hurtado, 1996). In chimpanzees, the same applies at ing an environmental cue (Relyea, 2002). Phenotypic
around the age of 30 (Hill et al., 2001). As humans plasticity also involves trade-offs between competing
senesce, changes in hormone levels map the process physical needs. For example, prolactin increases in
of aging and somatic degeneration. This process is association with breast-feeding and investment in
most prominent in regards to female reproductive sen- present offspring tends to suppress ovarian function
escence, otherwise known as menopause. Ova deple- and investment in future reproduction. The amount
tion leads to decreases in estrogen levels and greater of prolactin secreted is directly related to the amount
gonadotropin production. While the timing of meno- of nursing intensity. However the ovarian suppressive
pause and the extraordinary length of postreproductive effects of prolactin and this trade-off can be temp-
life is unique to humans, the endocrine signals of ered by greater insulin levels caused by enhanced
menopause seem to be common among mammals energy availability and somatic condition (Ellison
and other great apes (Austad, 1994; Videan et al., 2006). and Valeggia, 2003).
Senescence among males is not characterized by an
abrupt cessation of reproductive function. However,
significant hormone changes occur such as declines CONCLUSION
in testosterone and increases in FSH and LH (Harman
et al., 2001), which may result in compromised fertility In order to gain a more complete picture of the adap-
(de La Rochebrochard et al., 2006). Changes in hormo- tive function of endocrine factors, including the role of
nal milieu also results in changes in somatic compos- hormones in life history trade-offs and events, future
ition, including a decline in muscle mass, increased investigations need to move beyond simple snapshot
adiposity, and lower metabolic rates (Fukagawa et al., measurements of hormone levels. Potential fruitful
1990). The adaptive significance of these changes are areas of research include interactions between various
unclear although it has been suggested that age- hormones and greater awareness that many hormones
associated somatic composition changes may indicate exhibit actions beyond their standard definitions. For
a shift from investment in reproductive effort to survi- example, testosterone is tagged as a sex hormone
vorship or perhaps offspring care (Bribiescas, 2006b). whereas many of its effects clearly have important
metabolic implications. In a similar fashion, the effects
of hormones on immune function merit considerable
HORMONES AND PHENOTYPIC PLASTICITY attention, since it is in this association that trade-offs
with maintenance are likely to be evident. Additionally,
A cornerstone of life history and evolutionary theory is patterns and amplitude of pulsatility have only barely
the importance of phenotypic plasticity or the ability of been appreciated. Such investigations will rely upon
organisms to modulate a phenotype in response to an more sophisticated multiple-sampling regimens and
environmental challenge. Since environments and an understanding of potential hormone pulsatility sig-
selection pressures can change rapidly, it is seldom nals. A greater appreciation of adaptive, nonpathologi-
adaptive for an organism to maintain a rigid set of cal hormone variation is also needed.
phenotypes (Schlichting and Pigliucci, 1998). Some
phenotypic plasticity responses rely on distinct periods
of sensitivity while others are malleable throughout the DISCUSSION POINTS
organism’s lifetime. It can therefore be postulated that
along with phenotypes themselves, the range of pheno- 1. What are the common trade-offs associated with
typic plasticity of important traits related to growth, hormone variation?
maintenance, and reproduction are themselves adap- 2. How do hormones regulate energetic allocation
tive features. But what are the regulatory mechanisms decisions?
3. How do hormones affect time allocation decisions? placental tissue of normal pregnant women and patients
4. Many hormones are involved in growth and repro- with pre-eclampsia at term. European Journal of Endocrin-
duction. Are these actions unique to human growth ology, 147, 785–793.
and reproduction, or are they shared with other Blanks, A. M. and Thornton, S. (2003). The role of oxytocin
species? Explain any major differences and why/ in parturition. British Journal of Obstetrics and Gynaecol-
ogy, 110, 46–51.
how natural and sexual selections could have pro-
Bribiescas, R. G. (1996). Testosterone levels among Aché
duced such differences.
hunter/gatherer men: a functional interpretation of popu-
lation variation among adult males. Human Nature, 7(2),
163–188.
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9 Ethical Considerations
for Human Biology Research
Trudy R. Turner
With commentary by Michael P. Muehlenbein
The past 25 years have seen an ever increasing include: avoid falsifying data or plagiarizing; avoid
emphasis on and discussion of ethics in professional carelessness when collecting data; avoid falsifying
life. The Center for the Study of Ethics in the Profes- grant records; avoid mistreating or discriminating
sions at the Illinois Institute of Technology currently against others, specifically students, coworkers, and
has a library of over 850 Codes of Ethics for various employees; avoid giving professional advice on topics
professions. Professional societies often have ethics you are not qualified to discuss; avoid falsely represent-
modules online. Courses on ethics or ethics training ing a professional organization; report conflicts of
are recommended parts of graduate curricula. Medi- interest; avoid clandestine research that cannot be
cine, law, engineering, and business all have ethical published; follow rules of multiple authorship and be
standards and codes. The scientific community as a an objective peer reviewer. These are well established
whole also shares a set of guiding principles that have and agreed upon. However, the most difficult responsi-
been codified into a code of ethics for research and bilities a physical anthropologist or human biologist
practice. In addition, each academic discipline has its faces are often to the people we study. Discussion of
own set of standards and principles, since each discip- these responsibilities can be subsumed under a general
line has its own history and its own ethical dilemmas. discussion of bioethics.
Here I will briefly review ethical principles common to Bioethics, a special branch of applied ethics, is
the scientific community as well as some of the ethical concerned with human health and human subjects
dilemmas faced by human biologists. This is not a research. Bioethics sets forth standards and principles
comprehensive account. I direct the reader to the that have become the model for work in medicine and
volume Biological Anthropology and Ethics: from Repat- research. Formal bioethics began after World War II,
riation to Genetic Identity (Turner, 2005a) for a fuller in the wake of Nazi experimentation, with the
discussion of the issues presented here. Nuremberg Code. This Code sets forth explicitly the
Codes of ethics exist because every individual faces principle of voluntary consent and lists criteria that
choices. These codes provide a framework for making must be met before any experimentation can be done
informed choices in situations where there are conflict- on human subjects (Turner, 2005b). In the decades
ing obligations and responsibilities. The codes provide following Nuremberg, several ethical codes were
a framework of general principles for discussion and enacted by the US government, the National Institutes
choice. No code can anticipate each unique situation. of Health, the World Medical Association, and the
Discussion and reflection are vital to anticipate situ- Department of Health, Education and Welfare. In
ations that may require quick decisions. Anthropolo- 1974, Congress enacted the National Research Act,
gists (as evidenced in the American Anthropological which mandated an Institutional Review Board (IRB)
Association [AAA] Code of Ethics, the American Asso- review for all Public Health Service-funded research,
ciation of Physical Anthropologists [AAPA] Code of and authorized the establishment of the National Com-
Ethics) recognize a series of responsibilities – to the mission for the Protection of Human Subjects of Bio-
people with whom they work and whose lives they medical and Behavioral Research. The Commission
study, to scholarship, to science, to the public, to stu- produced a document, known as the Belmont Report.
dents and trainees, to employers, and employees. With The Belmont Report articulated three ethical prin-
these multiple levels of responsibility it can be difficult ciples: autonomy or respect for persons, beneficence,
to determine which takes precedence in a given situ- and justice. These principles are usually understood
ation. Linda Wolfe (2005) has reviewed the responsi- as do no harm, apply the rules of justice and fair distri-
bilities that anthropologists face that are common to bution, do not deprive persons of freedom and help
all scientists in the practice of their science. These others (for a fuller discussion, see Stinson, 2005). The
144
Ethical Considerations for Human Biology Research 145
Belmont Report has been codified into federal regula- identify practices that would no longer be considered
tions and is used by Institutional Review Boards (IRBs) wholly acceptable. However, these practices may have
in their analysis of research protocols. These IRBs are been fully acceptable and even far-sighted at the time
local and found at institutions conducting or support- research was conducted. Recently a controversy
ing human subjects’ research. Institutional Review occurred surrounding James Neel and his research
Boards are responsible for the review and approval of among the Yanomami. The controversy erupted a short
research activities involving human subjects. Their pri- time before a book by Patrick Tierney, Darkness in El
mary mandate is to protect the rights and safeguard Dorado (2000), was published. In proofs of the book,
the welfare of human research subjects. In 1981, final Tierney had accused Neel of starting a measles epidemic
Department of Health, Education, and Welfare by injecting local villagers with a virulent measles vac-
(DHEW) approval was given in 45 CFR 46, Subparts cine. These charges were withdrawn before the book was
A, B and C (Title 45 Public Welfare, Code of Federal published, due to a huge outcry by the scientific commu-
Regulations, Part 46 Protection of Human Subjects, nity about the validity of these claims. But controversy
1991). On March 18, 1983, Subpart D was added to continued, with some researchers claiming Neel and his
the regulations, providing additional protections for team did not do all they could to alleviate the measles
children who are subjects in research. Initially the epidemic among the Yanomami. Several professional
Department of Health and Human Services (DHHS, organizations, including the AAA, set up task forces to
the agency that replaced DHEW) regulations applied review all materials. Within the anthropological commu-
only to research conducted or supported by DHHS. nity the controversy quickly came to concern the
But, in June 1991, the United States published a seeming conflict between obligations to science and
common policy for federal agencies conducting or sup- humanitarian efforts. Those members of the task force
porting research with human subjects. That policy, charged with reviewing the Neel material (Turner and
which is known as “the Common Rule,” extended the Nelson, 2005) found that Neel worked very hard to alle-
provisions of 45 CFR Part 46, to fourteen other federal viate the measles epidemic he found in Venezuela.
agencies; it now governs most federally supported There were other issues in the Darkness in El
research. The composition and operation of each Dorado controversy that continue to have resonance
university or institution IRB must conform to the for researchers today. These include the nature of
terms and conditions of 45 CFR Part 46. (NIH Human informed consent, reciprocation for samples, and dis-
Research Protection Program, http://www1.od.nih. position of samples.
gov/oma/manualchapters/intramural/3014/). Since the
establishment of the IRB system, other federal commis-
sions, including the National Research Council, the INFORMED CONSENT
National Bioethics Advisory Commission, and the Presi-
dent’s Council on Bioethics, have continued to examine There are several excellent reviews of the history of
issues concerning human subjects and to prepare informed consent. Philosophers, ethicists, historians of
updated guidelines. Human subjects research must be science, and attorneys have all written about this (see
overseen by local IRBs. Funding by federal agencies will for example, Beauchamp and Childress, 1989; Gert
not be approved without IRB oversight and approval. In et al., 1997). Before the Nuremberg Report, most clin-
multi-institution or multi-national projects more than ical medicine researchers were guided by the principle
one IRB may be involved. Since every institution in this of beneficence and dealt little with the principle of
country has its own IRB and every country may have its autonomy. This principle of autonomy or respect for
own regulations, approval to do research can be cum- persons, articulated as voluntary or informed consent,
bersome. But as Long (2005, p.278) states, “As a general was of primary importance in the shaping of the
rule, investigators should simultaneously meet the Nuremberg Code, which resulted as a response to Nazi
highest standards of both our own culture and those of medical experimentation. The Nuremberg Code and
the research subjects’ culture.” According to Long others that followed presented an ideal for dealing with
(2005, p. 279) the current guidelines now “mandate that human subjects. However, the particulars of application
among other things, the researcher is responsible for of this ideal to real-life situations was not as well articu-
proper scientific design, monitoring participant rights lated. There were certainly also situations and research
and welfare in the course of research and ensuring that projects conducted before the current regulations when
all personnel on the research team are qualified and principles of informed consent were missing (one of the
trained in human subjects protections.” most egregious examples being the Tuskegee Syphilis
Until 45 CFR 46 was implemented oversight of Study, which ended in 1972). The real question in many
research projects was not well codified. It is certainly studies conducted before the implementation of the
possible to look back at research conducted in the years Belmont Report is how informed was informed consent.
between the Nuremberg Code and 45 CFR 46 and How well articulated were the goals, methods, and
146 Trudy R. Turner
consequences of the research? While these questions require them to return again and again to local, identi-
are important when dealing with relatively informed fied communities. Some researchers have had multi-
Western, English-speaking individuals, how were they decade relationships with their study populations.
handled with non-Western, non-English-speaking, indi- Over the decades, standards of what is included in
genous populations? informed consent have changed. Friedlaender (2005)
Recognizing this as a special case, the World Health gives a detailed account of his 35-year relationship
Organization (WHO) convened a working group which with groups in the Solomon Islands and the changing
met in 1962 and 1968 to discuss studies of “long-stand- standards of informed consent that he has imple-
ing, but now rapidly changing, human indigenous popu- mented in his work. The current standard is, of course,
lations” (Neel 1964). Two reports were produced, both full disclosure of the research project and the risks and
authored by James Neel (1964, 1968), which detailed the benefits. This includes returning to the population for
relationship and ethical obligations of researcher to additional consent if samples might be used for a
study population. Neel particularly emphasized six related, but not identical project. The best way to
factors of special importance: (1) The privacy and dig- describe the current paradigm is in terms of an on-
nity of an individual must be respected and anonymity going relationship between subjects and researchers,
of subjects must be maintained. (2) Satisfactory, but with subjects as active participants in research design
carefully considered, recompense should be given for and implementation.
participation in a study. (3) The local population should Researchers are conditioned to think about the
benefit from the study by medical, dental, and related impact of research on an individual – on his or her
services. (4) Attempts should be made to maintain con- health or psychological well being. It is important
genial social relationships with participants. (5) Learned now that the researcher think about the impact of the
individuals should be consulted. (6) There should be the research on the study population. The Belmont Prin-
utmost regard for cultural integrity of the group. ciples protect individual participants in research pro-
It is clear these principles were in place during the jects. But many anthropological studies are population
heyday of studies conducted under the Human Adapt- based and the findings of these studies can impact and
ability Section of the International Biological Program affect whole populations. Consultation and group con-
(Collins and Weiner, 1977). Informed consent was sent is now sought from populations. But group con-
sought, but not in the ways it is now sought. Turner sent leads to a new suite of questions (enumerated by
and Nelson (2002, 2005) conducted a survey of 14 Juengst, 1999; Turner, 2005b): “Who speaks for the
researchers working in the field during this time. They group? If the group is nested within a larger group,
asked specifically how information was conveyed to who represents the original group? What are the limits
individuals involved in studies. Every survey respond- of the group? What is the relationship between expatri-
ent stressed that there were individuals in the popula- ate groups and the community of origin? Does permis-
tions they worked with who did not participate. sion from a national government to conduct research
Voluntary consent was therefore assumed. Research- have meaning for the community being studied? How
ers either had government or local permission to con- does one obtain informed consent from an individual
duct their studies. In every case, researchers gave some or a group whose members have little understanding of
explanation of the motivation for the study. But some the project or the risks involved? How can the culture
of these explanations were not necessarily complete. of the population be taken into account in the design or
Researchers felt that perhaps local populations might implementation of the project? What are the implica-
not understand precisely the questions they were pur- tions concerning the disclosure of the identity of the
suing. Scientists who were part of the Yanomami group? Can consent be withdrawn sometime in the
expedition in the late 1960s have stated that the Yano- future? How? Can samples be withdrawn sometime in
mami were told that the researchers were going to look the future? How? Are there appropriate benefits for the
for diseases of the blood. This was true, but there were population under study?” This series of questions must
other things that were researched as well. Some Yano- be asked by every researcher engaged in research with
mami that have spoken to outsiders after the publica- human populations. In fact, these same questions are
tion of the Tierney book have stated that there was an asked by cultural anthropologists, archaeologists, skel-
expectation of greater medical benefit from the work. etal biologists, and any other researcher working with
identified human populations.
An example of group consent and consultation can
GROUP CONSENT be found in the work of O’Rourke et al. (2005) who
have been engaged in ancient DNA research with sev-
Physical anthropologists and human biologists are in a eral populations. Each of the populations O’Rourke
unique position – they are interested in the range of has worked with necessitated an individualized
human variation and they frequently study traits that approach for access to samples. Some communities
requested in-person meetings; others did not. Different trust between the investigator and the participant. In
communities had different restrictions on the size of medical studies in this country, compensation may take
samples. Working with Paleo-Indian remains for the form of some level of medical care. However, what
ancient DNA (aDNA) or skeletal biology studies in this are appropriate compensations for research studies
country requires adherence to Native American Graves conducted with non-Western, identified populations?
and Repatriation Act (NAGPRA) regulations. This may If a study includes medical personnel, some level of
mean that some of these studies cannot take place. On medical care may be given to the participants. But this
the other hand, some scientists (Larsen and Walker, is not necessarily the type of care individuals need.
2005) have been able to open discussions with Certainly there are some conditions where antibiotics
native peoples on the study and disposition of human or analgesics can be useful and even life saving. What if
remains. a person is identified as diabetic? A single visit from a
medical professional will not be sufficient to help this
person. Referrals to more long-term care facilities may
WEIGHING RISKS AND BENEFITS be in order. In the past, researchers have given many
items as compensation. Researchers usually select these
Distinctions are made in the Belmont Report between items in consultation with those familiar with the cul-
biological and behavioral research. In biological or ture. Food items, photos, tools, machetes, and cash have
medical research, risks can often be more clearly iden- all been given as compensation. Other items have been
tified than in behavioral research. But, behavioral given to the group or community. One of the more
research can cause emotional, psychological, or social recent examples of compensation involved technology
harm (Stinson, 2005). Embarrassment or social stigma transfer and training of individuals to use this technol-
can be real consequences of participation in a research ogy (Bamshad, 1999; Jorde, 1999).
project. An individual may find questions embarrass-
ing or might face social consequences if his or her
answers to questions were known. One of the most DATA SHARING
important risks to an individual is disclosure of iden-
tity. Institutional Review Boards are very aware of the Circular A-110 of the US Office of Management and
risks of this disclosure and will look closely at the ways Budget stipulates that data collected through grants
in which identity can be safeguarded. awarded by federal agencies such as National Insti-
Winston and Kittles (2005) describe the challenges to tutes of Health (NIH) and National Science Founda-
perceived identity that were sometimes generated by the tion (NSF) are public. Federal agencies encourage the
African Ancestry Project. Williams (2005) also discusses broad and rapid dissemination of information
some disclosure issues faced by descendents of Thomas throughout the scientific community reflecting the
Jefferson after a study of DNA from descendents of scientific ideal of an open community of scholars
Sally Hemings and the Jefferson family. Stigmatization pursuing novel ideas and avenues of research. Major
can also occur at the group level and this may be espe- complex electronic databanks already exist. Genetic
cially true for marginalized or identified populations. information is shared via the International Nucleotide
Members of a group might be stigmatized by having their Sequence Database, which includes GenBank, the
circumstances discussed. How can one avoid this DNA DataBank of Japan, and the European Molecular
situation? Researchers feel that a frank and full discus- Biology Laboratory. The NSF has a database initiative.
sion of this risk can lead to a negotiation between subject Data used by physical anthropologists, however, is
and researcher on the presentation of the results and often unique and difficult to obtain. It may not be pos-
the naming of the group as participant. Williams (2005) sible to obtain second sets of blood or saliva samples or
also suggests that constant vigilance during the planning measurements, or interviews from members of identi-
and execution of the project be paramount. fied communities. Individual and group consent and
confidentiality become major issues if samples are
shared. Specific questions about data sharing range
COMPENSATION from the definition of data to fair use for the individual
collecting the data (Turner, 2005c). The physical
There is often a huge differential between the researcher anthropology program of the NSF has a data-sharing
and the participant in studies in education, socioeco- requirement. However, the design implementation of
nomic status and access to resources. Researchers can this requirement is up to the individual researcher, but
and do compensate participants in research studies for must go beyond publication of results in a scientific
their time and effort. But the compensation must not be journal. Questions related to the ethics and the require-
so great as to compel participation in a study. In add- ments of data sharing are really just beginning in our
ition, this differential may also influence rapport and community.
148 Trudy R. Turner
IMPLEMENTING ETHICAL REFERENCES

STANDARDS
Bamshad, M. (1999). Session one: issues relating to popu-
lation identification, anthropology, genetic diversity
Discussions of ethics usually generate more questions and ethics. Symposium held at the University of
than answers. Field-work situations are unique. Issues Wisconsin-Milwaukee. http://www.uwm.edu/Dept/21st//
change from place to place and from time to time. projects/GeneticDiversity/session1.html (last accessed,
Ethical standards have also changed over time. There November, 2007).
are now laws and standards concerning research and Beauchamp, T. L. and Childress, J. F. (1989). Principles of
research subjects. In the vast majority of cases, Biomedical Ethics, 3rd edn. New York: Oxford.
researchers make their best possible efforts to behave Collins, K. J. and Weiner, J. S. (1977). Human Adaptability: a
according to the letter and the spirit of the law. But History and Compendium of Research in the International
there are judgment calls and the IRB system is in place Biological Programme. London: Taylor and Fraser.
Friedlaender, J. S. (2005). Commentary: changing standards
for oversight – so that someone else can add perspec-
of informed consent: raising the bar. In Biological Anthro-
tive. It is important, though, that ethics not be confined
pology and Ethics: from Repatriation to Genetic Identity,
merely to IRB oversight. Continual discussion, espe-
T. R. Turner (ed.). Albany, NY: SUNY Press, pp. 263–274.
cially during training, is important. Many training
Gert, B., Culver, C. M. and Clouser, K. D. (1997). Bioethics: a
programs offer specialized courses in ethics. Others Return to Fundamentals. Oxford: Oxford University Press.
include discussion of ethics in every class. In either Jorde, L. (1999). Session four: successful research collabor-
case, students and faculty need to continually engage ations. Anthropology, genetic diversity and ethics. Sympo-
each other in an assessment of ethical standards in sium held at the University of Wisconsin-Milwaukee.
professional life. http://www.uwm.edu/Dept/21st//projects/GeneticDiversity/
jorde.html (last accessed, November, 2007).
Juengst, E. (1999). Session one: issues relating to identifying
populations. Anthropology, genetic diversity and ethics.
DISCUSSION POINTS
Symposium held at the University of Wisconsin-Milwaukee.
http://www.uwm.edu/Dept/21st//projects/GeneticDiversity/
1. In the digital age, the treatment, storage, and trans- juengst.html (last accessed, November, 2007).
portation of sensitive data are particularly import- Larsen, C. S. and Walker, P. L. (2005). The ethics of bioarch-
ant. Storage of sensitive personal information on a aeology. In Biological Anthropology and Ethics: from
laptop may not be secured. What precautions must Repatriation to Genetic Identity, T. R. Turner (ed.). Albany,
be taken to secure this type of information? NY: SUNY Press, pp. 111–119.
2. How can one overcome the logistical issues associ- Long, J. C. (2005). Commentary: an overview of human sub-
ated with obtaining additional informed consent jects research in biological anthropology. In Biological
from remote populations? Anthropology and Ethics: from Repatriation to Genetic Iden-
3. What if a previously unknown condition is revealed tity, T. R. Turner (ed.). Albany, NY: SUNY Press, pp. 275–279.
during genetic screening? In many areas of the Neel, J. V. (1964). Research in Human Population Genetics of
world, referring a subject to a physician is not Primitive Groups. WHO Technical Report Series No. 279.
Geneva: World Health Organization.
feasible. What do you do?
Neel, J. V. (1968). Research on Human Population Genetics.
4. The disparity in wealth between a researcher and a
WHO Technical Report Series No. 387. Geneva: World
participant may influence rapport between the
Health Organization.
two. What are some methods to deal with this? O’Rourke, D. H., Hayes, M. G. and Carlyle, S. W. (2005).
5. There may be situations when a research agenda The consent process and DNA research: contrasting
and humanitarian concerns come into conflict. approaches in North America In Biological Anthropology
Discuss the expectations and limits of a researcher’s and Ethics: from Repatriation to Genetic Identity,
responsibility to the participant community. T. R. Turner (ed.). Albany, NY: SUNY Press, pp. 231–240.
Stinson, S. (2005). Ethical issues in human biology behav-
ioral research and research with children. In Biological
Anthropology and Ethics: from Repatriation to Genetic
ACKNOWLEDGEMENTS
Identity, T. R. Turner (ed.). Albany, NY: SUNY Press,
pp. 139–148.
I am grateful to Michael Muehlenbein for asking me to Tierney, P. (2000). Darkness in El Dorado. New York: W. W.
participate in this volume. I am also indebted to all the Norton.
authors of the volume on Biological Anthropology and Turner, T. R. (2005a). Biological Anthropology and Ethics: from
Ethics for their insights. I am also grateful to two Repatriation to Genetic Identity. Albany, NY: SUNY Press.
anonymous reviewers who helped greatly with the Turner, T. R. (2005b). Introduction: ethical concerns in
discussion questions. biological anthropology. In Biological Anthropology and
Ethics: from Repatriation to Genetic Identity, T. R. Turner Williams, S. R. (2005). A case study of ethical issues in
(ed.). Albany, NY: SUNY Press, pp. 1–13. genetic research: the Sally Hemings–Thomas Jefferson
Turner, T. R. (2005c). Commentary: data sharing and access story. In Biological Anthropology and Ethics: from
to information. In Biological Anthropology and Ethics: Repatriation to Genetic Identity, T. R. Turner (ed.). Albany,
from Repatriation to Genetic Identity, T. R. Turner (ed.). NY: SUNY Press, pp. 185–208.
Albany, NY: SUNY Press, pp. 281–287. Winston, C. E. and Kittles, R. A. (2005). Psychological and
Turner, T. R. and Nelson, J. D. (2002). Turner Point by Point. ethical issues related to identity and inferring ancestry of
El Dorado Task Force Papers. Final Report, vol.1, part 6. African Americans. In Biological Anthropology and Ethics:
Washington, DC: American Anthropological Association. from Repatriation to Genetic Identity, T. R. Turner (ed.).
Turner, T. R. and Nelson, J. D. (2005). Darkness in El Albany, NY: SUNY Press, pp. 209–229.
Dorado: claims, counter claims and the obligations of Wolfe, L. D. (2005). Field primatologists: duties, rights and
researchers. In Biological Anthropology and Ethics: from obligations. In Biological Anthropology and Ethics: from
Repatriation to Genetic Identity, T. R. Turner (ed.). Albany, Repatriation to Genetic Identity, T. R. Turner (ed.). Albany,
NY: SUNY Press, pp. 165–183. NY: SUNY Press, pp. 15–26.
Commentary: a Primer on Human
Subjects Applications and
Informed Consents
Investigators utilizing human subjects for any reason in (http://www.fda.gov/oc/ohrt/irbs/default.htm); the US

their research are charged with the vital responsibility National Institutes of Health Office of Extramural
of ensuring ethical standards of conduct. These stand- Research, grants policy on research involving human
ards are outlined by a number of governing bodies, subjects (http://grants.nih.gov/grants/policy/hs/index.
particularly the Department of Health and Human htm); the International Association of Bioethics (http://
Services, Office for Human Research Protections www.bioethics-international.org/); and the Association
(http://www.hhs.gov/ohrp/) and Office for Civil Rights for Practical and Professional Ethics (http://www.
(http://www.hhs.gov/ocr/) in the United States. Human indiana.edu/~appe/). Some of the basic information on
subjects committees, empowered by these governing human subjects applications is summarized in Table 9.1.
bodies, are then designated at the institutional level to Any project consisting of greater than minimal risk
provide oversight of human use in biomedical and to subjects requires full committee review. However,
behavioral research projects. Principle investigators US regulations allow certain types of research to be
and their teams are then responsible for ensuring the exempt from or expedited through reviews. Those that
safety and welfare of subjects and compliance with may be exempt include studies that constitute very
research protocols. This is initially accomplished by minimal risk of harm or discomfort, such as research
working with institutional review boards (human sub- involving normal educational practices with adults,
jects committees in particular) in a detailed application anonymous surveys and interviews, and analyses of
process prior to the initiation of research. existing data or biological specimens (with no identi-
Below is a brief introduction for newcomers to the fiers attached). Other applications can be expedited
human subjects committee application, including the through the review process if they constitute minimal
informed consent. This general information has been risk from invasive or noninvasive sample collection
compiled from a number of online sources (last (e.g., image, voice, body composition, biological fluid,
accessed August, 2009). Application format is certainly DNA, etc.), or certain behavioral observations. In all
specific to individual institutions. However, the gen- cases, applications are still read by at least an adminis-
eral guidelines are usually the same, drawn from basic trator or decentralized reviewer.
requirements laid forward by, among others, the US Certain research subjects require special attention,
Department of Health and Human Services Code of and research projects utilizing these subjects must be
Federal Regulations, Title 45 (Public Welfare), Part 46 evaluated via full panel review. This includes projects
(Protection of Human Subjects) (http://www.hhs.gov/ utilizing students, employees, and incarcerated indi-
ohrp/humansubjects/guidance/45cfr46.htm) and the viduals who are susceptible to coercion by teachers,
Health Insurance Portability and Accountability Act employers, and parole boards. If students are given
(HIPAA) (http://www.hhs.gov/ocr/hipaa/ and http:// course credit or extra credit for participating in
privacyruleandresearch.nih.gov/). Specific questions research projects, they should be allowed alternative
should be directed towards your institution’s review means to obtaining this credit if they do not wish to
board office, its human protections administrator and volunteer as research subjects. Permission from a
staff, as well as its HIPAA privacy board. Other useful legally authorized representative is necessary for
resources include the following: Public Responsibility minors and decisionally impaired individuals, includ-
in Medicine and Research (http://www.primr.org/); the ing those with cognitive disorders, those under the
US National Institutes of Health Office of Extramural influence of drugs or alcohol, or someone under
Research, certificates of confidentiality (http://grants. extreme emotional distress. For those participants
nih.gov/grants/policy/coc/index.htm); the US Food aged 7–17 in the United States, the participant’s assent
and Drug Administration, Guidance or Institutional must be obtained in addition to consent from a parent,
Review Boards, Clinical Investigators, and Sponsors advocate, or guardian. Other special subjects include
150
TABLE 9.1. Basic list of important considerations for preparation of human subjects applications.
1. Is your project exempt from review, or can it be expedited? This will depend on the type of data collected, methodology,
and the type of population used (i.e., vulnerable populations like minors, prisoners, pregnant women, etc.). See http://
www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm for categories.
2. For projects being conducted at multiple institutions or with multiple investigators, additional review board submissions may
be required. Biomedical and behavioral research conducted outside of the United States is expected to be conducted with
the same ethical and regulatory standards as research conducted within the United States.
3. Are all risks to participants minimized, including physical, emotional, monetary and other risks?
4. Include basic and detailed information in your application, but make sure that it is readable to a wide audience unfamiliar
with your type of work. Include a brief description of the purpose of the study, the anticipated length and location of your
study, the subject pool you are utilizing, including sex, ethnicity and age ranges, your ultimate sample size as well as
detailed inclusion and exclusion criteria for your study.
5. Explain how you will contact and enroll subjects. Include any advertisements in your application.
6. The informed consent document should be written in a nontechnical language that is understandable to all participants or
their representatives. Explain the purpose and procedures of the research, risks and benefits to participation, how
confidentiality will be maintained, how participation may be terminated, important contact information and, most
importantly, how participation is completely voluntary. Include the informed consent document in your application.
7. Include a detailed protocol for your project. Include any survey instruments with your application.
8. Thoroughly consider any risks of participation to your subjects. What alternatives to your procedures have been considered
and why are they not feasible? How will risks be minimized?
9. How are you going to protect participant confidentiality during data collection, storage, analyses, and presentation?
10. Carefully consider whether participation with monetary or course credit incentives are coercive.
11. Include in your application any documentation of investigator training in the protection of human research participants.
Do any of the investigators have significant financial interests in the subject of this research?
12. After approval by the human subjects committee, any changes to your project, including small ones, must be reapproved
by the committee before implementation into the protocol.
13. Continuing review applications, following expiration of the initial approvals, require a status report on the project, particularly
unanticipated problems involving risks to subjects.
pregnant women, fetuses, and newborns, all of which nov_2002.htm); the Medical Ethics Manual (2005) from
are particularly sensitive to adverse health outcomes. the World Medical Association (http://www.wma.net/e/
Some research may require that a researcher provide ethicsunit/resources.htm); the Universal Declaration on
participants with false information about the research Bioethics and Human Rights (2005) and the Universal
or withhold information about the real purpose of the Declaration on the Human Genome and Human Rights
research. Such deception may require debriefing (1997) from the United Nations Educational, Scien-
after study completion as well as a statement in the tific, and Cultural Organization (www.unesco.org/
informed consent form explaining that the full intent of shs/bioethics). Other Country-specific human subjects
the study may not be disclosed until completion. research legislation can be found at http://www.hhs.gov/
For projects being conducted at multiple institutions ohrp/international/HSPCompilation.pdf.
or with multiple investigators, additional review board Most human subjects committee applications and
submissions may be required. This is particularly the informed consent documents require similar basic
case with international projects. Biomedical and behav- information, with variations depending on level of
ioral research conducted outside of the United States is detail. You are usually first asked to provide a brief
expected to be conducted with the same ethical and description of the purpose of the study, possibly
regulatory standards as research conducted within the including specific hypotheses or problem statements
United States. Research must comply with laws of the that are easily interpretable to nonexperts. You should
host country, usually enforced through collaboration specify the anticipated length of your study, possibly
with a local research or educational institution. Some including a general scheduled timeline. You must
useful international resources include: the International specify the subject pool you are utilizing, including
Covenant on Civil and Political Rights (1996) from the sex, ethnicity, and age ranges. Does your research
Office of the United National High Commissioner for focus only on one sex or ethnicity? If so, why? Are your
Human Rights (http://www.ohchr.org/english/law/ccpr. subjects affiliated with a specific group, such as uni-
htm); the International Ethical Guidelines for Bio- versity students or members of a religious sect? Specify
medical Research Involving Human Subjects (2002) your ultimate sample size as well as detailed inclusion
from the Council for International Organization of Med- and exclusion criteria for your study. If there is a pos-
ical Sciences (http://www.cioms.ch/frame_guidelines_ sibility that the investigators can or will withdraw
152 Trudy R. Turner
subjects from participation, what are the conditions procedures have been considered and why are they not
for withdrawal? feasible? How will adverse events be reported?
An individual must be free from coercion to make Unique identifiers should be used to link subjects
the decision to participate in your study, and thus it is with their data and samples in order to maintain con-
necessary to specify how you will be contacting and fidentiality. The code list linking this information must
enrolling subjects. Will you be using media advertise- be kept in a secure place, such as a locked file cabinet
ments, classroom announcements, direct greetings, or a password-protected computer. How secure is your
etc.? Will the way you advertise the study inadvertently data if you are conducting the project over the inter-
coerce someone into participation? Where will recruit- net? Who will have access to the individual research
ment take place? Where will samples be procured or records? Will access be limited to only the principle
data collected? investigator, or will access also be granted to research
An inadequate informed consent can easily delay assistants, collaborators, and representatives of
the human subjects application process. It is a truism funding agencies? To further safeguard subject iden-
that consent must be voluntarily given by each research tity, outcomes of the research are usually only released
subject after he or she has been completely informed. and published in aggregate form. Information that
The consent document should be addressed to the sub- personally identifies individuals should not be released
ject, inviting him or her to participate in the study. It without prior written permission or as required by
should be written in a nontechnical language that is Federal or State laws (e.g., disclosure of reportable
understandable to all participants or their representa- diseases, abuse, intent to harm oneself or others,
tives (a 12-year-old reading level is a good benchmark), etc.). Finally, you must consider how participant con-
and it must be in the subject’s native language, in which fidentiality will be maintained when the study is over.
case a translator/interpreter may have to be employed. What will happen to the data/samples once you are
In some circumstances, the informed consent docu- done with them? Will information be deposited for
ment can be read to the participant. Studies involving future use or will it be destroyed? If there is a possibi-
anonymous participation with only minimal risks to the lity that a subject’s data or samples may be used for
subject may not require any informed consent, in which another related research project in the future, this
case an information sheet is still supplied to partici- must be stated in the original informed consent. Other-
pants. Anonymous surveys should still include a state- wise consent will have to be reobtained in the future.
ment to the effect that completing the survey indicates Participant benefits must be carefully considered.
that they agree to participate and are of appropriate age Often times the only benefit to subjects may be their
to participate. For web-based studies, information contribution to the body of knowledge. High monetary
about the study should be provided, and participants incentives are coercive, but some payment is frequently
should be required to click an “agreement” button provided, at a minimum to cover transportation costs,
before proceeding to the study task. meals, and lost wages. If the subject withdraws from
A detailed list of procedures used to gather infor- the study before completion, it will likely be necessary
mation must be included in your application and to distribute partial payment for time rendered. Keep
informed consent. Describe the order of events during in mind that your home institution’s accounting office
a typical session with each subject. How much time may also require that receipt of each participant’s com-
will it take? Include information regarding follow-up pensation be signed for. Sometimes payee addresses
visits, and include copies of all advertisements and and social security or other identification numbers
survey instruments with your application. must be recorded.
The risks of research with your human subjects Subjects sometime request to know their individual
must be thoroughly thought out and clearly defined, results, particularly in the cases of genetic, hormonal,
including all foreseeable immediate and long-term and infection diagnostics. This may be problematic,
risks of their participation. These may include physical however, because most analyses are not conducted
discomfort, injury or illness, anxiety, embarrassment, in clinically certified laboratories and thus results
lost of respect, loss of time and wages, altered behav- are not technically available for nonresearch purposes.
ior, loss of confidentiality, and so on. Are you investi- If subjects test positive for an infection, will you be
gating illegal behaviors or gathering information that providing medical treatment or only informing them
could make a subject uninsurable or unemployable? to see a physician? Most researchers in human evolu-
What is the likelihood of infection if you are collecting tionary biology are not qualified physicians and thus
blood samples? How will you minimize these risks cannot legally provide diagnoses and treatment. Other
from occurring? How do the anticipated benefits of things to consider may include: if injury results from
this project outweigh the risks? What is the rationale participation in your study, will subjects be provided
for the necessity of such risk? What alternatives to your with medical care, and will participants be further
compensated if your research results in eventual tech- information. A statement should highlight the com-
nological development? pletely voluntary nature of the subject’s participation
Most human subjects applications require contact and how refusal to participate or withdrawal at any
information from all personnel directly interacting with time will not result in penalty or loss of benefits to
subjects. Conflicts of interest need to be identified: do which the subject would otherwise be entitled, or
any of the investigators have significant financial inter- affect the subject’s medical care if the research is being
ests in the outcomes of the study? Furthermore, prior to conducted at a medical institution. Above the signa-
the release of funds, most granting agencies require ture line, a statement should be provided that the
documentation of investigator training in the protec- subject has read the consent form, has been given
tion of human research participants. This may include the opportunity to have all of their questions answered
simple online presentations and exams or even work- to their satisfaction, and agrees to participate. The
shop attendance. Several excellent web-based tutorials informed consent should be signed (or otherwise
can be found at the following: http://ohrp-ed.od.nih. recorded) and witnessed, and a copy supplied to the
gov/CBTs/Assurance/login.asp; http://cme.cancer.gov/ participant.
clinicaltrials/learning/humanparticipant-protections.asp; Review board approval is usually granted for up to
http://irb-prod.cadm.harvard.edu:8153/hirbert/hethr/ one year, after which a continuation or termination
HethrLogin.jsp; http://www.research.umn.edu/consent/; must be applied for. All changes in protocols, even
http://www.yale.edu/training/; http://www.indiana.edu/ minor ones, require reapproval from the institutional
~rcr/index.php. review board before the changed protocols can be
It is obvious that contact information of the implemented. This may all seem like a daunting task,
principle investigator must be supplied on the but one that is absolutely necessary for legal, moral,
informed consent documents. Additional information and ethical reasons. There is great satisfaction in doing
should include contact information for the human things right the first time, especially for something
subjects committee of the principle investigator’s as critical as the advancement of science with the
institution as well as any relevant foreign contact assurance of human welfare.
Part II
Phenotypic and Genotypic Variation
“Man is the only creature who refuses to be what he is.”

Albert Camus (1913–1960), The Rebel: an Essay on
Man in Revolt (1951), p. 11
155
10 Body Size and Shape: Climatic
and Nutritional Influences on
Human Body Morphology
William R. Leonard and Peter T. Katzmarzyk
INTRODUCTION These morphological and physiological differences

between organisms of different size are at the heart of
Since the initial spread of Homo erectus from Africa the relationship described by Bergmann’s Rule.
some 1.8 million years ago, the human lineage has col- Allen’s Rule, on the other hand, considers how
onized every major ecosystem on the planet, adapting to changes in shape can alter SA:mass ratios. For organ-
a wide range of environmental stressors (Antón et al., isms of the same size, the more elongated or linear the
2002). As with other mammalian species, human vari- shape, the greater the SA:mass ratio. Thus, for organ-
ation in both body size and morphology appears to be isms residing in tropical environs, a linear body plan –
strongly shaped by climatic factors. The most widely with less mass in the trunk and greater mass in the
studied relationships between body morphology extremities – will best help to facilitate heat dissipation.
and climate in mammalian species are those descri- In contrast, for arctic-adapted organisms, a body build
bed by “Bergmann’s” and “Allen’s” ecological rules. characterized by larger trunk size and shorter limbs
Bergmann’s Rule addresses the relationship between will reduce metabolic heat loss by minimizing SA/mass.
body weight (mass) and environmental temperature, Over the last 60 years, numerous studies have dem-
noting that within a widely distributed species, body onstrated that contemporary human populations gen-
mass increases with decreasing average temperature erally conform to the expectations of Bergmann’s and
(Bergmann, 1847). In contrast, Allen’s Rule considers Allen’s Rules, such that populations residing in colder
the relationship between body proportionality and tem- climes are heavier and have shorter relative limb
perature (Allen, 1877). It finds that individuals of a lengths, resulting in a decreased ratio of SA to body
species that are living in warmer climes have relatively mass (Schreider, 1950, 1957, 1964, 1975; Newman,
longer limbs, whereas those residing in colder environ- 1953; Roberts, 1953, 1973, 1978; Barnicot, 1959; Baker,
ments have relatively shorter extremities. 1966; Walter, 1971; Stinson, 1990; Ruff, 1994;
The physical basis of both of these ecological rules Katzmarzyk and Leonard, 1998). The most widely cited
stems from the differences in the relationship between research on this topic is the work by D. F. Roberts
surface area (cm2) and volume (cm3 proportional to (1953, 1978). In his 1953 paper, “Body weight, race
mass [kg]) for organisms of different size (Schmidt- and climate,” Roberts demonstrated a significant nega-
Nielson, 1984). Because volumetic measurements tive correlation between body mass and mean annual
increase as the cube of linear dimensions, whereas temperature, indicating that humans appear to con-
surface area increases as the square, the ratio of sur- form to Bergmann’s Rule. In subsequent work, Roberts
face area (SA) to volume (or mass) decreases as organ- (1973, 1978) showed that humans also conform to
isms increase in overall size. In addition, metabolic Allen’s Rule, such that populations living in colder
heat production in all animals is most strongly related regions have relatively shorter legs and larger relative
to body mass (e.g., Kleiber, 1975; FAO/WHO/UNU, sitting heights (RSH ¼ [sitting height]/[stature]) than
1985). Thus, in terms of thermoregulation, larger those groups inhabiting warmer regions.
organisms are better suited to colder environments In 1998, we re-examined the influence of temperature
because they produce more heat and have relatively on body mass and proportions, drawing on anthropo-
less SA through which to lose that heat. Conversely, metric data collected after Roberts’s pioneering work
small body size is better in warmer conditions, because in 1953 (Katzmarzyk and Leonard, 1998). Our analyses
these organisms will both produce less heat and have confirmed many of Roberts’s original findings. Specif-
relatively greater surface for dissipating that heat. ically, we found that the inverse relationship between
157
158 William R. Leonard and Peter T. Katzmarzyk
mass and temperature continues to persist for both TABLE 10.1. Geographic distribution of studies
men and women; however, the slope of the regression compiled for the current sample of males and females
was significantly shallower than that reported by and Roberts (1953) sample (males only).
Roberts. Likewise, the relationship that we found
Current sample Roberts sample
between RSH and temperature was more modest than
that of Roberts’s sample. These differences partly Region Males Females Males
reflect secular changes in growth and body size over African 44 42 28
the last half-century, and development of improved Australian 11 8 2
technology that moderates extreme temperature Melanesian 47 41 4
exposure during development. These findings under- American 55 47 16
score the importance of both nutritional and tempera-
European 17 18 20
ture stresses in shaping human variation in body size
Central Asian 6 7 2
and shape.
East Asian 11 8 29
Unlike most chapters in this book, the present
Polynesian 13 12 2
chapter will not only provide a review, but also a
South Asian 4 1 6
detailed reanalysis of the influence of climatic and
Indian 15 14 7
nutritional factors on worldwide human variation in
Total 223 198 166
body mass and proportions. We hope that this may
serve as an example of the application of modern
theory and methods in human evolutionary biology,
as outlined above as well as in Chapters 6 and 7 of this sitting height (cm; n ¼ 168 samples; 94 males;
volume. 74 females) and mean triceps skinfold thickness (mm;
First we examine the relationships between n ¼ 102 samples; 56 males, 46 females) were also avail-
selected anthropometric dimensions and mean annual able. Table 10.1 shows the geographic distribution of
temperature in the Roberts (1953) sample, and our the studies compiled in the current sample and in the
own worldwide sample (from Katzmarzyk and Roberts (1953) sample. The groupings follow those
Leonard, 1998). In exploring the influence of climate used by Roberts (1953). Additional information about
on body morphology in the two samples, we utilize the composition of the sample and its geographic dis-
indices (the body mass index [BMI] and SA/mass tribution is presented in Katzmarzyk and Leonard
ratios) not considered by Roberts and others in previ- (1998). Mean annual temperatures ( C) for the locales
ous work. Next, we consider the magnitude of patterns from which the anthropometric data were collected
of change in relations between climate and body size were obtained from climatic tables and atlases (Stein-
and proportions over the last 50þ years, and consider hauser, 1970, 1979; Gentilli, 1977; Schwerdtfeger,
the reasons for those changes. Finally, we examine the 1976; Lydolf, 1971; Willmott et al., 1981).
implications that this work for the use of anthropomet- From the sample means of height and weight com-
ric methods of nutritional health assessment in bio- piled from the literature, several derived indices were
medical and public health contexts. Increasingly, also calculated. These included: (1) the body mass
weight-for-height measures such as the BMI are being index (BMI; kg/m2); (2) body surface area (cm2);
used as a screening tool for assessing the risks of (3) surface area/mass ratio (SA/mass; cm2/kg); and
obesity around the world. Our findings suggest that (4) relative sitting height (RSH). The BMI was calcu-
simple indices such as the BMI must be applied with lated as (weight [kg])/(stature[m2]). Surface area was
caution when they are used to compare the relative risk estimated using the equation of Gehan and George
of obesity and associated chronic diseases in popula- (1970) as recommended by Bailey and Briars (1996):
tions from different ecological/environmental contexts.
lnSA ¼ 3:751 þ 0:422lnðstatureÞ þ 0:515lnðmassÞ
where stature is in cm, mass is in kg, and SA is in m2.

SAMPLE AND METHODS Surface area/mass was then determined as body SA
(cm2)/weight(kg). Relative sitting height was calculated
This study draws on the published data on mean stat- as: 100 (sitting height[cm])/(stature[cm]).
ure (cm) and body weight (kg) from 116 adult male
samples compiled by Roberts (1953) in his original
study on climatic influences on body mass. In addition, CLIMATIC INFLUENCES ON BODY WEIGHT
the primary sample that we compiled includes mean AND PROPORTIONS
stature and body weights for 223 male and 198 female
samples from studies published between 1953 and Table 10.2 presents the descriptive statistics for the
1996. For a subsample of these studies, data on mean anthropometric sample of Roberts (1953), and our
Body Size and Shape 159
TABLE 10.2. Descriptive statistics of anthropometric dimensions for the D. F. Roberts (1953) sample (males only),
and the current sample.
Roberts (males) Current (males) Current (females)
Measure n MeanSD n MeanSD n MeanSD

a d
Stature (cm) 116 163.7 6.6 222 165.4 6.5 197 154.3 6.0
Body weight (kg) 116 56.5 7.9b 223 61.6 9.5d 198 54.1 9.3
BMI (kg/m2) 116 21.0 2.0b 222 22.4 2.5 197 22.6 2.9
Surface area (m2) 116 1.61 0.14b 222 1.69 0.15d 197 1.53 0.15
SA/mass (cm2/kg) 116 287.1 16.5b 222 276.8 16.4d 197 286.8 18.9
d
Sitting height (cm) – – 94 85.1 3.7 74 80.7 3.4
c
RSH (%) – – 94 51.7 1.7 74 52.3 1.7
Triceps (mm) – – 56 7.7 3.4 d 46 14.1 7.0
Notes: Differences between the Roberts sample males and the current sample males are statistically significant at: P < 0.05; bP < 0.001.
a
Differences between current sample males and females are statistically significant at: cP < 0.05; dP < 0.001.
BMI, body mass index; RSH, relative sitting height; SA, surface area.
TABLE 10.3. Regression parameters for the relationships of body weight (kg), BMI (kg/m2), SA/mass (cm2/kg), and
RSH (%) versus mean annual temperature ( C) for the Roberts sample, and the males and females of the current sample.
Regression parameters
Sample/measure n Y-intercept b + SE R
Roberts (males):
Body weight (kg) 116 65.80 0.55 0.70 0.59***
2
BMI (kg/m ) 116 23.41 0.14 0.02 0.59***
2
SA/mass (cm /kg) 116 267.55 1.15 0.15 0.59***
Current males:
Body weight (kg) 223 66.86 0.26 0.06 0.27***
2
BMI (kg/m ) 222 23.62 0.06 0.02 0.22***
2
SA/mass (cm /kg) 222 267.00 0.49 0.11 0.29***
RSH (%) 94 52.97 0.06 0.02 0.37***
Current females:
Body weight (kg) 198 59.33 0.26 0.06 0.28***
2
BMI (kg/m ) 197 24.41 0.09 0.02 0.30***
2
SA/mass (cm /kg) 197 273.73 0.66 0.13 0.34***
RSH (%) 74 53.66 0.07 0.02 0.45***
Note: Correlations are statistically significant at: ***P < 0.001.

subsequent sample (Leonard and Katzmarzyk, 1998). shorter and lighter than their male counterparts, with
Our male sample is significantly taller, heavier (higher shorter sitting heights and lower estimated body
body weights and BMIs) and has a significantly lower surface areas. Conversely, SA/mass ratios and triceps
average SA/mass ratio than the Roberts sample. Note skinfold thicknesses are higher among the women.
that the relative differences in body weight between the Body mass indices of the female sample are compar-
two samples are larger than the changes in stature able to those of the males, with similar prevalence of
(þ9% vs. þ1%). Thus, we find that the prevalence of overweight and obesity (12.2% in males; 15.6% in
overweight and obesity (BMI 25 kg/m2) in the cur- females; n.s.).
rent sample is more than three times that of the The influence of mean annual temperature on
Roberts sample (12.2% vs. 3.4%; P < 0.001). selected anthropometric dimensions in both the original
The Roberts (1953) paper did not provide data for Roberts (1953) sample and our more recent sample is
females. The females of our sample are significantly explored in Table 10.3 and Figures 10.1–10.4. In each
(a) (b)
100 100
Roberts (males) Current (males)
r = –0.59 r = –0.27
90 90
80 80
Body weight (kg)
Body weight (kg)

70 70
60 60
50 50
40 40
30 30
–20 –15 –10 –5 0 5 10 15 20 25 30 35 –20 –15 –10 –5 0 5 10 15 20 25 30 35
Mean annual temperature (°C) Mean annual temperature (°C)
(c)
100
Current (females)
90 r = –0.28
80
Body weight (kg)
70
60
50
40
30
–20 –15 –10 –5 0 5 10 15 20 25 30 35

Mean annual temperature (°C)
10.1. Relationship between body weight (kg) and mean annual temperature ( C) in (a) males of the
Roberts (1953) sample, (b) males of the current sample, and (c) females of the current sample. In all
three samples, body weight is inversely related to temperature. The correlation between body weight
and temperature is stronger in the Roberts sample compared to males and females of the current
sample.
group, weight and the BMI are negatively correlated inhabiting hotter regions have physiques that maxi-
with mean annual temperature (Figures 10.1 and mize surface area/mass to promote heat dissipation.
10.2). In males of the present sample, the correlations However, as noted above, the correlations for the
of mean annual temperature with weight and BMI are Roberts (1953) sample (r ¼ 0.59) are much stronger
0.27, and 0.22, respectively, whereas the correlations than in the current male and female samples (r ¼ 0.29
for females are 0.28 for body mass and 0.30 for the for males; r ¼ 0.34 for females). Additionally, the
BMI. In the Roberts (1953) sample, the correlations regression slopes of the Roberts sample are twice as
are stronger (r ¼ 0.59 for both weight and BMI), and large as those seen for in the current samples (b ¼ 1.15
the slopes of the best fit regressions are significantly [Roberts] vs. 0.49 [males] and 0.66 [females];
steeper than in the current male and female samples P < 0.001).
(weight: b ¼ 0.55 [Roberts] vs. –0.26 [males], 0.26 Finally, we see that in the current sample RSH is
[females]; P < 0.001; BMI: b ¼ 0.14 [Roberts] vs. 0.06 negatively correlated with temperature in both sexes
[males], 0.09 [females]; P < 0.001). (r ¼ 0.37 in males; r ¼ 0.45 in females; see Table 10.3
The SA/mass ratios are positively associated with and Figure 10.4). This relationship is consistent with
mean annual temperature in all three of the samples the expectations of Allen’s Rules, indicating that trop-
(Figure 10.3). This indicates that populations of colder ically adapted populations have a more linear body
climes have body plans that minimize surface area build, with relatively longer limbs and shorter trunks.
to mass to reduce metabolic heat loss, whereas those In contrast, populations of high latitude environments
(a) (b)
36 36
34 34
r = –0.59 r = –0.22
32 32
30
30
BMI (kg/m2)
28
BMI (kg/m2)
28
26
26
24
24
22
22
20
20
18
18
16
16
14
–20 –15 –10 –5 0 5 10 15 20 25 30 35 –20 –15 –10 –5 0 5 10 15 20 25 30 35
Mean annual temperature (⬚C) Mean annual temperature (⬚C)
(c)
36
Current (females)
34 r = –0.30
32
30
BMI (kg/m2)
28
26
24
22
20
18
16
–20 –15 –10 –5 0 5 10 15 20 25 30 35

Mean annual temperature (⬚C)
10.2. Relationship between the body mass index (BMI; kg/m2) and mean annual temperature ( C) in
(a) males of the Roberts (1953) sample, (b) males of the current sample, and (c) females of the current
sample. In all three samples, the BMI is inversely related to temperature. The correlation between BMI
and temperature is stronger in the Roberts sample compared to males and females of the current sample.
are characterized by a more stout body plan with (WHO) (2006), at least 400 million adults worldwide
shorter extremities and a relatively larger trunk. As are obese. If current trends continue, this number is
with the previously discussed analyses, the correlations projected to increase to 1.1 billion by 2030 (Kelly et al.,
between RSH and temperatures reported by Roberts 2008). These dramatic increases in body size over the
(1978, pp. 21–22) were stronger than those observed last two generations have altered the relationship
in the current sample ( 0.62 for males; 0.65 for between climate and body morphology across human
females). In addition, the regression coefficients for populations.
the Roberts (1978) sample were twice those of the The results presented in Table 10.4 further investi-
current samples (b ¼ 0.12 vs. 0.06 for males; 0.13 gate the temporal changes in the relationship between
vs. 0.07 for females). climate and body morphology within our sample. The
table presents results of multiple regression analyses in
which both mean annual temperature and year of
SECULAR TRENDS IN BODY WEIGHT study publication were entered as independent vari-
AND PROPORTIONS ables. We see that even after adjusting for the influence
of climate, both body weight and BMI have increased
Obesity and associated metabolic disorders have now over time, whereas SA/mass ratios have significantly
emerged as major global health problems. According to declined. In contrast, RSH does not appear to show a
recent estimates by the World Health Organization consistent pattern of change over time. The temporal
(a) (b)
340 340
320 r = 0.59 320 r = 0.29
300 300
SA/mass (cm /kg)
SA/mass (cm2/kg)
2
280 280
260 260
240 240
220 220
200 200
–20 –15 –10 –5 0 5 10 15 20 25 30 35 –20 –15 –10 –5 0 5 10 15 20 25 30 35
(c)
340
Current (females)
320 r = 0.34
300
SA/mass (cm /kg)
2
280
260
240
220
200
–20 –15 –10 –5 0 5 10 15 20 25 30 35

10.3. Relationship between the ratio of body surface area:mass (SA/mass; m2/kg) and mean annual
temperature ( C) in (a) males of the Roberts (1953) sample, (b) males of the current sample, and
(c) females of the current sample. In all three samples, the SA/mass is positively related to tempera-
ture. The correlation between SA/mass and temperature is stronger in the Roberts sample compared
to males and females of the current sample.
(a) (b)
56 56
Males r = –0.37 Females r = –0.45
Relative sitting height (%)
54 54
Relative sitting height (%)
52 52
50 50
48 48
46 46
–20 –15 –10 –5 0 5 10 15 20 25 30 35 –20 –15 –10 –5 0 5 10 15 20 25 30 35

Mean annual temperature (⬚C) Mean annual temperature (⬚C)
10.4. Relationship between the relative sitting height (RSH; %) and mean annual temperature ( C) in
(a) males and (b) females of the current sample. In both males and females, RSH is inversely related to
temperature.
TABLE 10.4. Multiple regression analyses of the influence of mean annual temperature and “year of study publication”
on body weight, BMI, SA/mass, and RSH.
Independent variables
Dependent variables n Constant Temperature (b + SE) Year (b + SE) Model R2
Males:
Body weight (kg) 223 165.05 0.27 0.06*** 0.12 0.06 0.09***
BMI (kg/m2) 222 80.75 0.06 0.02*** 0.05 0.02** 0.09***
2 ***
SA/mass (cm /kg) 222 690.90 0.50 0.11 0.22 0.11 0.10***
***
RSH (%) 94 108.67 0.06 0.02 0.03 0.02 0.16***
Females:
Body weight (kg) 198 –229.70 0.28 0.06*** 0.15 0.06* 0.11***
BMI (kg/m2) 197 –98.24 0.10 0.02*** 0.06 0.02** 0.14***
2 *** **
SA/mass (cm /kg) 197 905.77 0.68 0.13 0.32 0.12 0.15***
***
RSH (%) 74 33.39 0.07 0.02 0.01 0.02 0.21***
Note: *P < 0.05; **P < 0.01; ***P < 0.001

(a) (b) (c)

70 24 300
Roberts
Current
23
SA/mass (cm /kg)
Body weight (kg)
65 290
BMI (kg/m )
2
2
22
60 280
21
55 270
20
50 19 260
< 15C > –15⬚C < 15C > –15⬚C < 15C > –15⬚C
Temperature zone (⬚C) Temperature zone (⬚C) Temperature zone (⬚C)
10.5. Mean (SEM) values of (a) body weight (kg), (b) body mass index (BMI) (kg/m2), and (c) SA/
mass (m2/kg) for males of the Roberts (1953) and the current samples residing in “colder” (<15 C) and
“warmer” (15 C) climates. For all three measures, the differences between the Roberts and current
samples are much larger in the warmer climate samples.
changes are statistically significant for body weight, Among women, the temporal trend for RSH has been
BMI, and SA/mass in the female sample. For men, essentially flat (b ¼ 0.01; P ¼ 0.50).
the secular trend is statistically significant for BMI The marked changes in body size over time are not
(b ¼ 0.05; P < 0.01), and approaches statistical signifi- same across all regions of the world. Rather, the
cant for the weight (b ¼ 0.12; P ¼ 0.07) and SA/mass increases in body mass have been disproportionately
(b ¼ 0.22; P P ¼ 0.056). larger among populations of the tropics. This point is
The temporal increases in body mass appear to be evident in Figure 10.5, which shows the differences in:
greater in women than men. The regression coeffi- (a) weight; (b) BMI; and (c) SA/mass among men of the
cients indicate that after controlling for temperature, Roberts (1953) and current samples for groups living
average gains in body weight were 0.12 kg/year in men in areas with mean annual temperatures of <15 C
and 0.15 kg/year in women, whereas the increases in (“colder”) and 15 C (“warmer”). Differences in body
BMI were 0.05 and 0.06 kg/m2 a year for men and weight between the two samples are about 50% greater
women, respectively. among populations of the warmer climates, as com-
Relative sitting heights have shown modest pared to those of colder environments (differences of
changes over time. Among men, there has been a þ6.9 kg [þ13%] vs. þ4.7 kg [þ8%]). Similarly the dif-
decline in RSH over the last 50 years, a trend that ferences in BMI in the warmer climes are twice those
approaches statistical significance (b ¼ 0.03; P ¼ 0.16). of the colder regions (differences of þ2.0 vs. þ1.0 kg/m2).
Conversely, declines in SA/mass ratios are twice as large in two large US samples (NHANES I and the Tecumseh
in colder environs (differences of 0.15 vs. 0.08 cm2/kg). Community Health Study). Norgan (1994b) also found
Thus while there has been a general, worldwide RSH to be strongly correlated with the BMI, and
increase in body mass over the last 50 years, the argued that differences in body proportions shape the
increases appear to be disproportionately larger in relationship between BMI and body composition
tropical regions. across populations.
In light of the strong influence that RSH has on
the BMI, it is reasonable to expect that the relation-
CLIMATE, BODY PROPORTIONS AND THE BMI: ship between BMI and body fatness may vary with
IMPLICATIONS FOR THE ASSESSMENT OF climate. The extreme examples of climatic differences
NUTRITIONAL STATUS in the BMI versus fatness relationship can be seen
when we compare data from the Australian Abori-
The results presented thus far clearly indicate that gines and Inuit of the Canadian Arctic. Norgan
climate and dietary/nutritional factors both play (1994a) has shown that traditionally living Australian
important roles in shaping patterns of interpopula- Aborigines studied before the 1970s had very low
tional variation in adult body size and proportions BMIs, suggestive of chronic undernutrition, yet had
around the globe. This finding has important implica- skinfold thicknesses that indicated adequate nutri-
tions for the use of anthropometric indices for assess- tional status. Conversely, early work among Inuit
ing physical nutrition status (Frisancho, 1990, 2008; men and women has shown that despite having BMIs
Gibson, 2005). The implications are particularly crit- that were at or above the threshold for “overweight,”
ical for considering the use of the BMI for assessing they were relatively lean, as reflected in both skinfold
risks of both under- and over-nutrition. Over the last measures and estimates of body fatness from hydro-
15 years, the BMI has become the most widely used static weighing (Shephard et al. 1973; Rode and
standard for assessing nutritional status of adults in both Shephard, 1994).
the United States and throughout the world (Shetty and Figure 10.6 examines the relationship between BMI
James, 1994; WHO, 1995, 2000, 2004). Current WHO and RSH for men and women of the current sample.
(1995) recommendations advocate using the following The correlations between RSH and BMI in the sample
BMI ranges for discerning different levels of nutritional are 0.48 for men and 0.58 for women, similar to those
well-being in adults over the age of 18 years: (1) under- reported by Norgan (1994b) for analyses of 95 male
nutrition: <18.5 kg/m2; (2) “healthy”: 18.5 24.9 kg/m2; and 63 female samples from human populations
(3) overweight: 25.0 29.9 kg/m2; and (4) obese: 30 kg/m2. around the world. Among men, each percent increase
Yet, accumulating research in human nutritional in RSH is associated with a 0.58 kg/m2 increase in BMI.
science suggests that a single set of BMI cut-offs may For women, the slope of the best fit regression is
not be appropriate for all human populations. In par- steeper, with each percent increase in RSH translating
ticular, recent work by Deurenberg and colleagues into an increase of 0.84 kg/m2 in BMI. These relation-
(Deurenberg et al., 1998; Deurenberg-Yap et al., 2000; ships imply that at the extremes of human RSHs, from
Deurenberg-Yap and Deurenberg, 2003) indicates 46 to 55%, the corresponding average BMI differences
that the WHO cut-off points for overweight and obesity are about 5 kg/m2 in men (mean BMIs of 19.1 vs. 24.3
do not effectively apply to Asian populations who kg/m2) and 7 kg/m2 in women (mean BMIs of 17.0 vs.
appear to have a different BMI versus body fat relation- 24.5 kg/m2). Thus, for adults with extremely linear
ship than European populations. These conclusions builds (i.e., low RSHs), average BMIs tend to cluster
are consistent with anthropometric studies of indigen- in the underweight to low healthy range, whereas those
ous populations living in different environments with very high RSHs have mean BMIs that approach
throughout the world (e.g, Norgan, 1994a, 1994b; the overweight range.
Shephard and Rode, 1996; Leonard et al., 2002; Snodgrass It is also clear from Figure 10.6 that populations
et al., 2006). from colder climates tend to cluster in the upper end of
Much of the debate surrounding the appropriate- the relationship, having high BMIs and RSHs, despite
ness of a single set of BMI cut-offs for assessing nutri- the recent trend for tropical populations to show more
tional status has overlooked the central question of rapid increases in body mass. Body mass indexes of
what factors may be responsible for producing differ- colder climate populations (<15 C) are significantly
ent relationships between BMI and body fatness across higher than their warmer climate peers in both men
different populations. It is clear that variation in body (24.3 vs. 21.9 kg/m2; P < 0.001) and women (25.0 vs.
proportions and body morphology play a strong role 21.4 kg/m2; P < 0.001). Similarly RSH among popula-
shaping variation in the BMI. Garn et al. (1986a, tions from cooler climes average 1.4% greater in men
1986b), for example, found that BMI was strongly cor- (52.8% vs. 51.4%; P < 0.001) and 1.6% greater in women
related with measures such as RSH and chest breadth (53.4% vs. 51.8%; P < 0.001).
(a) (b)
30 < 15 ⬚C
30 Females < 15 ⬚C
Males ≥ 15 ⬚C ≥ 15 ⬚C
Fit line for Total r = 0.58 Fit line for Total
r = 0.48
28 28
26
BMI (kg/m2)
26
BMI (kg/m2)
24 24
22
22
20
20
18
18
46 48 50 52 54 56 46 48 50 52 54 56
Relative sitting height (%) Relative sitting height (%)
10.6. Relationship between the body mass index (BMI) (kg/m2) and relative sitting height (RSH) (%) in
(a) males and (b) females of the current sample. The BMI is positively correlated with RSH in both
sexes, suggesting that body proportion exert a strong influence on the BMI. Additionally, note that
populations from colder climes cluster to the upper right corner of the graph, having high BMIs
and RSHs.
(a) (b)
18 35
Males <15 ⬚C Females <15 ⬚C
≥ 15 ⬚C r = 0.82 ≥ 15 ⬚C
r = 0.72
16 Fit line for Total Fit line for Total
30
Triceps skinfold (mm)
Triceps skinfold (mm)
14
25
12
20
10
15
8
10
6
4 5
18 20 22 24 26 28 30 18 20 22 24 26 28 30 32
BMI (kg/m2) BMI (kg/m2)
10.7. Relationship between triceps skinfold thickness (mm) and the body mass index (BMI) (kg/m2) in
(a) males and (b) females of the current sample. The triceps skinfold measures are positively correl-
ated with BMI for both sexes. Note, however, that populations from colder climates generally fall
below the regression line (particularly among males), suggesting that they are leaner than expected for
their BMIs.
To directly test the influence of climate on the rela- increases in obesity rates over the last 50 years
tionship between the BMI and body fatness, we draw (McGarvey, 1991; McGarvey et al., 1993; Flegal et al.,
on the subsample of 102 groups for which we have 2002; Ogden et al., 2006). We also find that in both
measurements of triceps skinfold thickness, BMI, and sexes, the populations from colder regions generally
mean annual temperature. Figure 10.7 shows the plot fall below the regression line, suggesting lower than
of triceps versus BMI for males and females. As expected levels of body fatness for a given BMI.
expected, the two measures are strongly positively cor- Table 10.5 compares the standardized residuals
related, r ¼ 0.72 in males and 0.82 in females (P < 0.001 (z-scores) from the sex-specific triceps versus BMI
in both sexes). The populations clustering in the upper regressions for populations from warmer and colder
right-hand corners of both the male and female graphs regions. Populations of colder climes have lower values
(Figures 10.7 a and b) include Samoans and Mexican than those of warmer climates, with the differences
Americans, both groups that have shown marked being statistically significant for males ( 0.79 vs. 0.17;
P < 0.05) and the pooled sample ( 0.51 vs. 0.12; set of BMI cut-offs to assess physical nutritional status
P < 0.01). These findings indicate that for a given in populations around the world. In using the BMI
BMI, populations residing in cooler climates have to assess obesity risks, particular attention should be
lower levels of body fatness than those residing in given to body proportionality. For populations with
warmer environs. extreme body proportions (e.g., RSH < 50% or >54%),
Multiple regression analyses produce similar additional anthropometric measures (e.g., skinfolds
results on the joint influences of temperature and and circumferences) may be needed to accurately
BMI on body fatness (Table 10.6). Among males both assess risks of overweight and obesity.
BMI and temperature are positively associated with
variation in triceps skinfold measures, and together
explain 57% of the variation in fatness. Among women, DISCUSSION
the relationship between BMI and fatness is more com-
parable across groups, as temperature is not signifi- The analyses presented here clearly demonstrate that
cantly associated with the variation in fatness after climatic factors continue to exert an important influ-
controlling for the influence of BMI. ence on body size and proportions among human
Thus, we see that climate-related variation in body populations around the world. Variation in body mass
morphology has a significant influence on the relation- (both weight and BMI), SA/mass and RSH within our
ship between the BMI and body fatness. At the same current sample broadly conforms to the expectations
BMI, individuals from colder climates are, paradoxic- of Bergmann’s and Allen’s Rules. However, it is equally
ally, leaner than expected based on international refer- clear that these relationships have not remained static
ences, whereas those of warmer regions are fatter. over time, but rather, have changed in response to
These climatic differences appear to be associated with shifting socioeconomic and ecological circumstances.
variation in body proportions. Relative sitting height is Indeed, the differences in the statistical relationships
strongly positively correlated with BMI, such that high found between the current sample and the Roberts
RSHs (as seen in arctic populations) are associated (1953, 1973, 1978) samples highlight important insights
with greater BMIs, while lower RSHs (seen in tropical about the avenues through which climate and ecology
groups) are associated with lower BMIs. These find- influence human biological variation.
ings suggest serious limitations in applying a single It is widely recognized that climate can influence
aspects of body morphology through a number of differ-
ent pathways, including temperature, rainfall, ultravio-
let (UV) radiation, and ecological productivity (i.e.,
TABLE 10.5. Standardized residuals (z-scores) of the
triceps skinfold versus. Body mass index regression
resource availability). In addition, humans can employ
for samples from colder and warmer climates. a number of different adaptive strategies to deal with
environmental stressors, ranging from shorter-term
Colder Warmer
physiological and developmental responses to longer-
(temp. <15 C) (temp. 15 C)
term genetic (Darwinian) adaptations (see Chapter 2
Sample N Mean SD N Mean SD of this volume). In discussing the application of
Males 10 0.79 0.91 46 0.17 0.93* Bergmann’s and Allen’s Rules to human populations, it
Females 9 0.20 1.25 37 0.05 0.93 is most often assumed that these relationships largely
Total 19 0.51 1.09 83 0.12 0.93** (or exclusively) reflect genetic adaptations to thermal
stress (e.g., Schreider, 1975; Ruff, 1994). Yet, there is
Note: Differences between the colder and warmer samples strong evidence to show these patterns are also the prod-
are different at: *P < 0.05; **P < 0.01.
uct of other environmental factors (such as nutrition)
operating through nongenetic adaptive mechanisms.
TABLE 10.6. Multiple regression analyses of the influence of BMI and mean annual temperature on triceps skinfold
thickness.
Independent variables
Dependent variables n Constant BMI (b + SE) Temperature (b + SE) Model R2
Males 56 15.52 0.96 0.12*** 0.77 0.03** 0.57***

***
Females 46 28.65 1.81 0.19 0.03 0.05 0.68***
Note: **P < 0.01; ***P < 0.001

BMI, body mass index.
Improvements in both nutrition and public health Although the multiple regression analyses failed to
over the last half century have contributed to secular document a secular trend in body proportions in the
trends in growth of stature and body mass in popula- current sample (see Table 10.4), is it clear that the
tions throughout the world (e.g., Roche, 1979). Declin- relationship between RSH and temperature in the cur-
ing rates of childhood malnutrition in the developing rent sample is different from that reported by Roberts
world (de Onis et al., 2000) have contributed to the (1978). Unfortunately, because we do not have
relatively larger increases in body mass among tropical Roberts’s raw data on body proportions, we cannot
populations documented here (Figure 10.5). These explore the nature of the differences in the same detail
disproportionate increases in mass among populations that we did with the body weight and BMI differences.
of the tropics help to explain the marked reductions Nonetheless, it appears that changes in food availabil-
in the strength of the associations of body weight and ity and Westernization of dietary habits may be
BMI with mean annual temperature in the current responsible for reducing global variation in RSHs, thus
sample relative to the Roberts sample. These findings explaining the lower correlations between RSH and
further suggest that the very strong inverse relation- temperature observed in the current sample.
ship between weight and temperature initially reported Finally, this work also has practical applications for
by Roberts was partly attributable to differences in diet the development of anthropometric standards for
and nutrition, as well as differences in thermal stress. assessing nutritional status. Our findings highlight
Recent analyses by Kelly et al. (2008) suggest that these some of the limitations in using a single set of BMI
trends are continuing, such that the developing regions norms for assessing risks of under- and over-nutrition
of the world are projected to have the greatest propor- around the world (Shetty and James, 1994; WHO,
tional increases in the number of overweight and obese 1995). It appears that climatic influences on body pro-
adults over the next 20 years. portionality play a strong role in shaping the relation-
Nutritional and developmental factors also appear ship between the BMI and body fatness across diverse
to play a role in shaping variation in body proportions. human populations. Paradoxically, populations of
Work by Frisancho et al. (1975, 1980; Stinson and colder climates tend to have lower levels of body fatness
Frisancho, 1978) among Quechua children of the for a given BMI, a pattern typified by arctic populations
Lamas region of lowland Peru provides important such as the Inuit of North America (Shephard and Rode,
insights into the role of ecology in shaping the develop- 1996). In contrast, tropically adapted populations such
mental changes in body proportions. This research as the Australian Aborigines have relatively higher levels
compared the growth of lowland Quechua children of fatness than suggested by their BMI values (Norgan,
from Lamas to Quechua children of the same genetic 1994a). These differences emphasize the need for cau-
background living in the highland region of Junin. tion when interpreting BMI values among populations
Stinson and Frisancho (1978) found that the immi- with extremely high or low RSHs. For these groups
grant Quechua children to the warm and humid low- in particular, it will be important to include a broader
lands had more linear body builds than their peers range of anthropometric measures (e.g., skinfolds, cir-
from the cold, high altitude regions. The authors cumferences) to provide an accurate picture of body
attributed the differences in body proportions between composition and potential risks of chronic diseases.
the two groups to the influence of temperature and
altitude stressors. These results also demonstrate the
role of developmental acclimatization in promoting CONCLUSIONS
significant differences in body proportions among
two populations with similar genetic backgrounds Human biologists have long recognized the important
living in radically different environments. role that climate plays in shaping body size and shape.
A growing body of research is also documenting the The analyses presented in this chapter have re-exam-
influence of nutrition on the development of body pro- ined the application of Bergmann’s and Allen’s Rules
portions during childhood growth. It is now recognized for understanding climatic variation in human body
that nutritional stress and poor growth during early size and proportions. The classic work of D. F. Roberts
childhood disproportionately affects the growth of long (1953, 1973, 1978) demonstrated that humans broadly
bones (Tanner, 1978). Hence, improvements in nutri- conform to these classic ecological rules. He found that
tion during growth and development are associated across a diverse sample of human populations, body
with not only taller overall stature, but longer relative mass, and RSH were inversely correlated with mean
leg lengths and thus, lower RSHs (Frisancho, 2007). annual temperature, consistent with the predictions of
Such developmental changes in body proportions Bergmann’s and Allen’s Rules, respectively.
may help to explain the observed differences in the Our current analyses, drawing on anthropometric
relationship between RSH and temperature between studies published after Roberts (1953) initial pioneer-
the current sample and that of Roberts (1978). ing work, confirm some, but not all of his conclusions.
The inverse relationships between body mass (as both Bailey, B. J. R. and Briars, G. L. (1996). Estimating the
body weight and BMI) and temperature continue to surface area of the human body. Statistics in Medicine,
persist for both men and women; however, the correl- 15, 1325–1332.
ations are lower and the slopes of the regressions are Baker, P. T. (1966). Human biological variation as an adaptive
shallower than those reported by Roberts. Similarly, response to the environment. Eugenics Quarterly, 13, 81–91.
Barnicot, N. A. (1959). Climatic factors in the evolution of
the relationships between RSH and temperature in
human populations. Cold Spring Harbor Symposia on
men and women of the current sample are also more
Quantitative Biology, 24, 115–129.
modest than those reported by Roberts (1978). These
Bergmann, C. (1847). Uber die verhaltniesse der warmeoko-
changes in the relationship between body morphology nonomie der thiere zu ihrer grosse. Gottingen Studien, 1,
and climate over the last 50 years, in part, reflect secu- 595–708.
lar change in the growth of body size and proportions. de Onis, M., Frongillo, E. A. and Blossner, M. (2000). Is child
Improvements in nutritional health, particularly malnutrition declining? An analysis of changes in levels of
among impoverished tropical populations, have pro- child malnutrition since 1980. Bulletin of the World Health
duced notable changes in body mass and proportions. Organization, 78, 1222–1233.
These results underscore the importance of both Deurenberg, P., Yap, M. and Van Staveren, W. A. (1998).
nutritional and temperature stresses in shaping devel- Body mass index and percent body fat: a meta analysis
opmental changes in human variation in body size and among different ethnic groups. International Journal of
shape. Moreover, they also have important implica- Obesity, 22, 1164–1171.
tions for the use of anthropometric indexes such as Deurenberg-Yap, M. and Deurenberg, P. (2003). Is a re-evalu-
ation of WHO body mass index cut-off values needed? The
the BMI as tools for assessing of nutritional status
case of Asians in Singapore. Nutrition Reviews, 61, S80–S87.
and chronic disease risks.
Deurenberg-Yap, M., Schmidt, G., Van Staveren, W. A., et al.
(2000). The paradox of low body mass index and high body
fat percentage among Chinese, Malays and Indians in
DISCUSSION POINTS
Singapore. International Journal of Obesity, 24, 1011–1017.
Flegal, K. M., Carroll, M. D., Ogden, C. L., et al. (2002). Preva-
1. Discuss the physical principles that are thought to
lence and trends in obesity among US adults, 1999–2000.
underlie Bergmann’s and Allen’s “ecological rules.” Journal of the American Medical Association, 288, 1723–1727.
2. Discuss how ongoing trends in global climate Food and Agriculture Organization, World Health Organiza-
change may influence interpopulational variation tion, and United Nations University (FAO/WHO/UNU)
in body mass, BMI, and body proportions (e.g., (1985). Energy and Protein Requirements. Report of Joint
relative sitting height). FAO/WHO/UNU Expert Consultation. WHO Technical
3. Discuss the utility and the limitations of the use of Report Series, no. 724. Geneva: World Health Organization.
the BMI as the preferred measure for assessing Frisancho, A. R. (1990). Anthropometric Standards for the
risks of overweight and obesity in the United States Assessment of Growth and Nutritional Status. Ann Arbor,
and around the world. MI: University of Michigan Press.
4. Discuss the pros and cons of have a single set of inter- Frisancho, A. R. (2007). Relative leg length as a biological
national BMI norms for quantifying the prevalence marker to trace the developmental history of individuals
and populations: growth delay and increased body fat.
rates of obesity and overweight in adult populations.
American Journal of Human Biology, 19, 500–508.
Frisancho, A. R. (2008). Anthropometric Standards: an Inter-
active Nutritional Reference of Body Size and Body Compos-
ACKNOWLEDGEMENTS
ition for Children and Adults. Ann Arbor, MI: University of
Michigan Press.
We are grateful to Professor Michael Muehlenbein for
Frisancho, A. R., Borkan, G. A. and Klayman, J. E. (1975).
the opportunity to contribute to this volume. Addition- Pattern of growth of lowland and highland Peruvian Quechua
ally, we thank Dr. Marcia Robertson and two anonym- of similar genetic composition. Human Biology, 47, 233–243.
ous reviewers for their comments and suggestions on Frisancho, A. R., Guire, K., Babler, W., et al. (1980). Nutri-
this chapter. This work was supported in part by a tional influence on childhood development and genetic
grant from the Natural Sciences and Engineering control of adolescent growth of Quechuas and Mestizos
Research Council of Canada (OGP-0116785). from the Peruvian lowlands. American Journal of Physical
Anthropology, 52, 367–375.
Garn, S. M., Leonard, W. R. and Hawthorne, V. M. (1986a).
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11 Human Adaptation to High Altitude
Tom D. Brutsaert
INTRODUCTION features acquired through lifelong exposure to hypoba-

ric hypoxia. The term indigenous (as in indigenous
As of 1995, over 140 million people worldwide lived at altitude native) will specifically refer to an individual
altitudes exceeding 2500 m (Niermeyer et al., 2001). with deep altitude ancestry who belongs to a popula-
The effects of hypobaric hypoxia – defined as a low tion that may have experienced natural selection in
environmental oxygen partial pressure – on cellular the past. In South America, archaeological evidence
metabolic function, growth and development, physical suggests the presence of Native Americans as early as
activity, reproduction, and human health have made 12 000 years ago (Lynch, 1990), and current indigenous
high altitude a unique setting in which to investigate high-altitude groups (the Aymara and Quechua) can
human adaptation. This is especially true for traits trace altitude ancestry back to at least 4000–6000 years
that are directly or indirectly related to oxygen (O2) ago, which marks the domestication of many highland
transport. Following Niermeyer et al. (2001), the term plant and animal species (llama, alpaca, potatos,
adaptation will be used to refer to a feature of struc- etc. . . .) (MacNeish and Berger, 1970; Lynch, 1990).
ture, function, or behavior that is beneficial and On the Himalayan plateau, there is evidence of paleo-
enables survival in a specific environment. Such fea- lithic human habitation as early as 25 000–50 000 years
tures may be genetic in origin, although features that ago (Zhimin, 1982). These paleolithic populations may
arise via developmental and/or physiological processes not have been ancestral to current populations, but
may also be termed adaptations if they enable survival genetic and linguistic studies of Tibetans suggest a
(see Chapter 2 of this volume). The term genetic time frame of habitation that goes back at least many
adaptation will refer to a heritable feature that was thousands of years (Torroni et al., 1994). Thus, in both
produced by natural selection (or other force of the Andes and the Himalayas, there has been sufficient
evolution) altering allele frequencies over time. A time for the operation of natural selection. However, it
developmental adaptation will refer to an irreversible is worth noting that there is little direct support for
feature that confers survival benefit and is acquired the hypothesis of genetic adaptation, i.e., to date there
through lifelong exposure to an environmental stress are no known gene (allele) or haplotype frequencies
or stressors. Developmental features that arise without that are unique to an indigenous high-altitude native
clear adaptive benefit will be termed developmental population with demonstrable effects on mortality/
responses. Finally, the term acclimatization will refer fertility under the conditions of hypobaric hypoxia.
to a time-dependent physiological response to high This chapter is organized into eight sections as
altitude, which may or may not be adaptive. follows: Section I defines hypoxia and provides an
Around the world, various regional populations introduction to the well-known biological effects of
show a wide diversity of time-depth exposure to alti- low environmental O2. Section II reviews the physi-
tude providing a “natural experiment” to test hypoth- ology of O2 transport as a basic understanding is cri-
eses of developmental and/or genetic adaptation tical for subsequent discussions of human adaptation.
(Moore, 1990). The term native (as in high-altitude or Section III provides several examples of the process of
highland native) will be used generally to identify an acclimatization to altitude, mainly to distinguish accli-
individual born and raised at high altitude, independ- matization from other modes of adaptation that are
ent of ancestry. For example in North America, some more central to the interests of human evolutionary
high-altitude natives of the Rocky Mountains with physiology, i.e., genetic and developmental adaptation.
lowland European origins may trace altitude ancestry Sections IV and V, respectively, focus on the physical
back ~150 years. This is not long enough for genetic work capacity (exercise) and reproductive perform-
adaptation, but such altitude natives may show unique ance of highland natives in hypoxia. These two areas
170
Human Adaptation to High Altitude 171
have been widely studied at high altitude and are con- (Figure 11.1). Note that FiO2 is constant with altitude.
sidered as important “adaptive domains,” following a For example, the ambient PO2 at 3000 m where Pb
conceptual framework that was originally described by is ~525 mmHg is ~70% of the sea-level value, or
Mazess (1978). An adaptive domain is an area of life 525 mmHg 0.21 ¼ 110 mmHg. This definition of hyp-
where the relative benefit (or significance) of a specific oxia is not particularly helpful from a functional stand-
adaptive response can be evaluated or defined. For point, and some distinction must be made between
example, if large lungs are adaptive in hypoxia, then hypoxia per se and the level of hypoxia (or the ambient
benefit must be defined with reference to an adaptive PO2) where measurable effects on human physiology
domain like reproductive performance, i.e., do women occur. The latter depends on the physiological system,
with larger lungs produce babies with lower mortality the outcome measure, and the individual. For example,
risk? In most cases, adaptive significance is difficult at the modest altitude of 1500 m, some very good
to ascertain. Thus, Section VI evaluates specific struc- athletes begin to experience decrements in aerobic
tural and/or functional traits of the oxygen transport capacity, and some visitors may note a transient hyper-
system that differ between highland and lowland popu- ventilation on first exposure (Maresh et al., 1983). In
lations, without a priori reference to an adaptive this chapter, most of the populations under consider-
domain. Where possible, the significance of a specific ation live above 2500 m where there are clear effects on
trait is considered relative to health and disease, repro- cellular metabolic processes underlying diverse human
ductive performance, exercise performance, growth activities and human health. Some of these effects
and development, and/or nutrition and energy use. are briefly considered here to emphasize that hypoba-
Section VII focuses on genetic studies of altitude adap- ric hypoxia is a formidable environmental stressor.
tation, and Section VIII offers areas of future research. This is precondition for research approaches that focus
on adaptive response.
Linear postnatal growth and development is nutri-
SECTION I: WHAT IS ENVIRONMENTAL ent and O2 flow dependent (note: prenatal growth is
HYPOXIA? discussed more fully in Section V below). Beginning
with the studies of Paul Baker and his students in
Environmental hypoxia is defined with reference to Nunoa, Peru (e.g., Frisancho, 1969), it has been sug-
“normoxia,” which is simply the O2 availability at sea- gested that hypoxia per se slows overall linear growth
level with 760 mmHg atmospheric pressure and a frac- and delays sexual maturation. In the Andes, where the
tional O2 concentration (FiO2) of about 0.21 (i.e., 21%). majority of growth studies have been conducted, much
The latter represents the composition of the earth’s of the delay is probably established at birth as a result
atmosphere. For dry air, the normoxic partial pressure of intrauterine uterine growth retardation, with little
for O2 (PO2) is about 160 mmHg, or 760 mmHg 0.21. catch-up growth thereafter (Greksa, 2006). At least
Hypobaric hypoxia refers to a lower than normoxic some of the growth delay is attributable to poor health
PO2 due to lower ambient pressure as one rises and nutrition in the research populations, but hypoxia
through the air column with increasing altitude likely has an independent effect evidenced by the
Barometric pressure (Pb) by altitude

100
Leadville,
700 Colorado 90
Percentage of sea-level value
(~3000 m)
600 80
Highest permanent human 70

500 habitation, La Riconada,
Peru (~5100 m) 60
Pb (mmHg)
400 Lhasa, Tibet and La Paz, 50

Bolivia (~3600 m)
300 40
30
200 Mount
Everest 20
(~8850 m)
100 10
0 0
0 2000 4000 6000 8000
Above sea-level (m)
11.1. Barometric pressure decreases with increasing altitude starting at sea-level. The highest
permanent human habitation is likely the small town of La Riconada, in Peru (West, 2002).
172 Tom D. Brutsaert
.
∆V O2max with increasing altitude Pre-eclampsia is ~3 times more common above 3000 m
80 (Palmer et al., 1999; Keyes et al., 2003).
70 Various diseases are also associated with hypoxia,
60
or exacerbated by hypoxic exposure. For example, ini-
tial exposure to altitude can lead to acute mountain
ml / min / kg
50
sickness (AMS) in some individuals, with prevalence
40 and severity depending on altitude and rate of ascent.
30 Acute mountain sickness is usually transient, but often
precedes or is associated with more serious and poten-
20
tially fatal complications like pulmonary or cerebral
10 edema. Lifelong or chronic hypoxic exposure is associ-
0 ated with a disease known as chronic mountain sick-
0 2000 4000 6000 8000 10000
ness (CMS), characterized by excessive polycythemia
Altitude (m)
: (high red blood cell level), severe hypoxemia (low blood
11.2. V O2max decreases with altitude, approximately 10% per O2 levels), and in some cases moderate or severe
1000 meters after 1500 meters. Data points: are updated from
Buskirk et al. (1967) and represent mean V O2max values from
pulmonary hypertension which may evolve to cor
studies of lowland native males who were exposed to hypobaric pulmonale, leading to congestive heart failure (Leon-
hypoxia. The length of exposure varies between studies: (from Velarde et al., 2005).
acute exposure to several weeks of exposure), but V O2max
does not change much with ventilatory acclimatization to
altitude (Bender et al., 1989). Some of the studies represented,
particularly those at extreme altitude, were carried out in a
SECTION II: THE PHYSIOLOGY OF O 2
hypobaric chamber. TRANSPORT FROM ENVIRONMENT TO CELL
Given the O2 poor environment of high altitude, the O2

delayed growth of European populations at altitude transport system is logically an area of major focus.
who generally live under relatively good socioeconomic This physiological system is frequently conceptualized
conditions (Greksa et al., 1988). as a linear sequence of functional and structural steps
Aerobic exercise is also an O2 dependent process. that brings oxygen into the body for delivery to cellular
One measure of performance is the maximal oxygen mitochondria (Figure 11.3). At the mitochondrial level,
:
consumption (V O2max) reflecting the integrated func- O2 fulfills its role as the final electron acceptor in the
tioning of pulmonary, cardiovascular, and muscle process of oxidative phosphorylation to produce
metabolic systems to obtain, deliver, and consume O2 adenosine triphosphate (ATP). Examples of functional
during maximal exertion. Buskirk et al. (1967) was the components of the O2 transport system include the
: :
first to quantify the decrement in V O2max (DV O2max) ventilation rate or the cardiac frequency (heart rate),
with increasing altitude in lowland men of mostly both of which can be regulated physiologically to
European origins, showing about a 10% decrease in increase or decrease O2 flux. Examples of structural
performance for every 1000 m additional altitude components include the pulmonary volume, the mass
beginning at about 1500 m (Figure 11.2). of the left ventricle, or the mass of red blood cells in
Reproductive performance is likely sensitive to circulation. Structural components may possess some
hypoxia, including fertility, and fetal and early infant regulatory capacity, but generally not in physiological
mortality (see Section V). Anecdotally, historical time, i.e., in seconds or minutes. For example, increa-
accounts describe reproductive difficulties encoun- sing red blood cell production at altitude requires
tered by early Spaniards in the Andes, with the best weeks. Increasing total lung volume requires exposure
known of these accounts claiming a 50-year period of to hypoxia during growth and development (see
infertility for Spanish women in the colonial city of Section VI).
Potosı́, Bolivia, at 4100 m! These effects are difficult The process of O2 transport from environment
to ascribe to hypoxia alone given the social, cultural, to cell involves, essentially, two convective and two
and nutritional factors that impact fertility, but it is diffusive steps in series, as shown in Figure 11.3. Con-
worth noting that fecundity/fertility in nonaltitude vection is the movement of a fluid (like air or blood),
native rodent species at altitude is significantly lower while diffusion is the movement of a molecule or ion
(Martin and Costa, 1992). Also, the lowest birthweights from a region of higher to lower concentration. The
and highest rates of infant mortality in the United first step, pulmonary ventilation (VE, L/min), or the
States occur in Colorado counties with the highest movement of air into and out of the lung, is convective.
mean altitudes (Moore, 2003). A contributing factor Functionally, VE is the first line of defense in the face
may be pre-eclampsia during pregnancy, a condition of hypoxia and it has the purpose of maintaining con-
that increases mortality risk of both mother and fetus. stant values of the alveolar oxygen and carbon dioxide
Ambient PO2 ~ 160 mmHg

(sea level, dry air) STEPS OF O2 TRANSPORT
V, l/min 1. Pulmonary ventilation (V),

Lung convective movement of O2
PALV O2
O2
2. Pulmonary diffusion
Blood
Blood O2 content (CaO2) =
Part O2
[Hb, g/dl] ⫻
(1.34 ml/dl) ⫻ 3. Blood flow, convective
Q= Hb:O2
(SaO2, %) HR ⫻ SV movement of O2
O 2 delivery =
(CaO2, ml/dl) ⫻
4. Peripheral diffusion of
(Q, L/min) O2 O2 to the mitochondria
Cell Mitochondria
11.3. The oxygen transport system has essentially four steps, two convective (pulmonary ventilation
and blood flow), and two diffusive (pulmonary and peripheral, i.e., muscle diffusion). The structural/
functional parameters that determine O2 delivery to the cell are indicated including; VE, pulmonary
ventilation; [Hb], hemoglobin concentration; SaO2, arterial oxygen saturation; CaO2, arterial oxygen
content; SV, stroke volume; HR, heart rate; and Q, cardiac output. See text for further details.
partial pressures (PAO2 and PACO2, respectively). The vein has a PO2 similar to that of alveolar gas PO2 i.e.,
alveolar ventilation (VA) is that proportion of VE that ~100 mmHg. But, this is not always the case. At alti-
participates in gas exchange, taking into account the tude, or sometimes during extremely strenuous exer-
fact that the conducting airways of the lung are cise, full equilibration between alveolar gas and
an “anatomic dead-space” where gas exchange cannot arterial blood PO2 may not take place, a condition
occur. The VA is not usually measured directly, but known as diffusion limitation. Diffusion limitation
this chapter will make reference to the concept of an causes a widening of the alveolar-arterial partial pres-
“effective VA.” Effective VA is assessed by consideration sure difference (A-a)DO2 as PaO2 becomes less than
of the functional consequence of breathing which is to PAO2. A widening of the (A-a)DO2 may also occur from
maintain/change gas partial pressures in the lung and a condition known as ventilation-perfusion mismatch,
thus circulation. also common at altitude, but without belaboring the
Note that PAO2 at sea-level is approximately details, it is important simply to realize that there are
100 mmHg, or about 60 mmHg lower than the ambient limits to the pulmonary gas exchange process. If one
PO2, and that PO2s fall at every subsequent step of the sees a small (A-a)DO2 at altitude, this is a good indica-
O2 transport chain from environment to cell. For this tion of an efficient gas exchange process, and from
reason, physiologists often refer to an “O2 cascade” an evolutionary or developmental perspective, one
driven by the partial pressure gradients at every step. might hypothesize adaptations in either functional
Importantly, PAO2 depends on ambient PO2, and so the or structural components of the pulmonary system to
overall PO2 gradient driving the diffusion of O2 from account for it.
lung to cell is reduced at altitude. VE itself is controlled The ambient PO2 and the process of VE together
in a complex manner by both central (brain) and determine PaO2. In turn, PaO2 determines the satur-
peripheral chemoreceptors. The latter are known as ation of hemoglobin with O2 (SaO2) according to the
the carotid and aortic bodies, and these sense changes Hb-O2 dissociation curve (Figure 11.4). The nonlinea-
in arterial blood gases (PaO2 and PaCO2) brought about rity of the Hb-O2 curve has several important physio-
through low ambient PO2 or increased metabolic logical implications. Above a PaO2 of about 60, where
demand for O2. the Hb-O2 curve is relatively flat, large changes in PaO2
The first diffusive step (pulmonary diffusion) is have little effect on SaO2. However, below ~60 mmHg,
from alveolar gas to blood across the pulmonary- or on the “steep” part of the Hb-O2 curve, small
capillary membrane. At rest and at sea-level, alveolar changes in PaO2 produce large changes in SaO2. In
and capillary blood partial pressures equilibrate rap- practical terms, this means that SaO2 is fairly resistant
idly so that blood leaving the lung via the pulmonary to altitudes up to about 2500 m, but will rapidly
Hb:O2 dissociation curve

100
90
Hb:O2 saturation, SaO2 (%)

80
70
60
50
40
30
20
10
0
0 20 40 60 80 100 120
Blood oxygen partial pressure (PO2)/(mmHg)
11.4. The partial pressure of oxygen in the blood (PO2) determines the saturation of hemoglobin with
oxygen (SaO2) according the hemoglobin-oxygen dissociation curve. Approximate arterial partial
pressures at sea-level, 1000, 2000, 3000, and 4000 meters are indicated. From (Severinghaus, 1979).
decrease thereafter. SaO2, hemoglobin concentration enlargement of the uterine artery (a structural par-
[Hb], and the O2-binding capacity of hemoglobin (a ameter). Similarly, increased placental size (struc-
constant at 1.34 ml O2/g hemoglobin) together deter- ture), analogous to increased pulmonary volume,
mine the O2 content of blood per unit volume, or would increase surface area for O2 diffusion and
CaO2-ml O2 per dl blood. CaO2 multiplied by blood thus increase O2 delivery to the fetus. The physiology
flow determines O2 delivery. Blood flow, of course, is of O2 delivery to the fetus in highland populations
the second convective step of the O2 transport process, has been researched extensively by Moore and col-
and is determined by cardiac output (Q) and regulation leagues and is discussed in more detail in Section VI
of regional blood flow by vasodilation/vasoconstriction below.
of arterioles to capillary beds. In turn, Q is determined
by heart rate (HR) and stroke volume (SV). The final
step of O2 delivery is peripheral diffusion of O2 into SECTION III: ACCLIMATIZATION TO
the cell down a diffusion gradient from capillary to HYPOBARIC HYPOXIA
mitochondria, where mitochondrial PO2 may be just
a few mmHG. In general, an understanding of how acclimatization
Given the importance of reproductive performance to high altitude affects a specific trait or feature is a
at altitude, it is important to also consider the physio- prerequisite before analysis of how population trait
logy of O2 delivery to the fetus. The fetus receives distributions are conditioned by developmental
nutrients from uterine arteries that derive from the exposure to hypoxia and/or by population genetic
maternal arterial circulation. The uterine arteries branch background. Some traits are very sensitive to acclima-
out into a dense capillary network known as the tization state, particularly ventilatory traits, and their
placenta, which serves as a gas exchange organ analysis from a developmental and/or evolutionary
between independent maternal and fetal circulations. perspective is therefore difficult. In other specific
Thus, O2 delivery to the fetus involves an additional cases, populations may not show the expected acclima-
diffusive step across the placenta. Like O2 delivery to tization response. For example, Tibetan populations
skeletal muscle, O2 delivery to the fetus is a function are characterized by [Hb] not different from sea-level
of uterine artery blood flow, [Hb], and SaO2. The normative values, counter to the expectation of hema-
student of human evolutionary physiology should tological acclimatization (see below and Section VI for
again consider the various structural or functional further discussion).
parameters that could be regulated (physiologically, As described, the term acclimatization refers to a
developmentally, or across evolutionary time) to time dependent, short-term, and reversible physiolo-
optimize O2 delivery to the fetus under conditions gical response to an environmental stress or stressors.
of hypobaric hypoxia. For example, O2 delivery could To illustrate the concept, two text-book examples
be upregulated by increasing uterine artery blood are considered here: (1) ventilatory acclimatization;
flow (a functional parameter), perhaps via and (2) hematological acclimatization. Ventilatory
acclimatization involves the regulation of breathing by fitness state, and acclimatization state. Thus, partition-
the nervous system including respiratory centers in the ing the effects of genes, development, and/or environ-
:
brain and peripheral chemoreceptors that are sensitive ment on V O2max is difficult. Compared to sea-level
to changes in blood PCO2, pH, and PO2. On initial residents in hypoxia, many studies have documented
:
exposure to hypoxia, the peripheral chemoreceptors a relatively high V O2max (ml/min/kg) in Andean (Elsner
(primarily the carotid bodies) sense changes in blood et al., 1964; Kollias et al., 1968; Mazess, 1969a, 1969b;
gas partial pressures and signal an increase in VE that Frisancho et al., 1973; Baker, 1976) and Himalayan
manifests within seconds to minutes (hyperventila- natives (Sun et al., 1990a; Ge et al., 1994b, 1995;
tion). This hyperventilation is progressive and reaches a Zhuang et al., 1996). Indigenous altitude natives also
:
plateau after 5–6 days (Huang et al., 1984; Smith et al., appear to experience smaller decreases in V O2max
:
2001). Hyperventilation causes transient decreases in (▵V O2max) when exposed to increasing hypoxia
PaCO2 and increases in blood pH to produce a respira- (Elsner et al., 1964; Velasquez, 1966; Baker, 1969;
tory alkalosis. Alkalosis may persist even after acclima- Frisancho et al., 1973; Vogel et al., 1974; Way, 1976;
tization, but over days there is some compensation Hochachka et al., 1991; Brutsaert et al., 2003; Marconi
:
to normalize blood chemistry, in part because of the et al., 2004). For example, ▵V O2max values in indigenous
action of the kidney which increases bicarbonate ion groups have been reported as between ~30% and 80%
excretion. In humans, the end of ventilatory acclima- of the decrement in lowland comparison groups.
tization is marked by a stability in VE, PaCO2, and pH. It is a difficult problem to explain the higher mean
:
The functional result is that individuals maintain a V O2max values of indigenous high-altitude natives. Is
:
higher VA to partially offset the decreases in SaO2 and the higher V O2max due to population genetics, develop-
CaO2. It should be emphasized that this process does mental exposure to hypoxia, or is it due to differences
not return the body to a sea-level physiological state. in lifestyle, particularly physical activity patterns?
Rather, SaO2 levels remain low depending on the spe- Consider the analyses shown in Figures 11.5 and 11.6.
:
cific altitude. Hematological acclimatization involves Figure 11.5 plots mean V O2max values (ml/min/kg) by
the hormone erythropoietin which stimulates an altitude for indigenous altitude-native males grouped
increase in the production of red blood cells from by region. These mean values were taken from the
precursor cells in the bone marrow. This process takes literature based on studies conducted over the past
place over weeks with a resultant increase in the
oxygen carrying capacity of blood. 100
90
O2 saturation (%)
SECTION IV: DO HIGH-ALTITUDE NATIVES 80

HAVE ENHANCED WORK CAPACITY AT
70
ALTITUDE?
60
Physical work is an important human activity, i.e., it is 50
an adaptive domain that is dependent on O2 availabi-
40
lity. The question addressed here is whether high- 0 2000 4000 6000
altitude natives have higher upper limits of work cap- 30
acity in hypoxia compared to their counterparts from
sea-level? Work capacity is a general term, but specific 25
Hb (g /100ml)
aspects of work performance may be measured inclu-

:
ding the maximal oxygen consumption (V O2max, or 20
aerobic capacity), the endurance capacity, and the
work efficiency/work economy. 15
:
Aerobic capacity (VO2max) 10
0 2000 4000 6000
:
V O2max is usually measured on a treadmill or cycle Altitude (m)
:
ergometer by progressively increasing work-load over 11.5. Published mean V O2max values from studies of Andean
a 10–15-minute period in order to obtain a 1-minute and Himalayan males taken from the literature. Mean values for
average of maximal O2 consumption. It is not surpris- indigenous altitude natives are superimposed on the sea-level
: native reference data (i.e., lowland native males from Figure
ing that V O2max decreases with increasing altitude
11.2) across the altitude range from 3000–5500 meters. P-value
(Figure 11.1). But, there is substantial variation in the is for a test of the: hypothesis that Andeans have higher mean
magnitude of the decrease between individuals depen- altitude specific V O2max compared to lowland native males
ding on age, gender, body-weight, body-composition, (sea-level reference) using regression analysis.
.
VO2max: highland groups
(a) Reference (sea-level natives) Andeans Himalayans
65
60
55 Andeans-vs.-Reference, P = 0.002
50
ml / min / kg
45
40
35
Reference
30
25
2500 3000 3500 4000 4500 5000 5500 6000
Meters
Reference (sea-level natives) Developmentally acclimatized

(b)
65
60
55 Developmentally acclimatized-vs.-
Reference, NS
50
ml / min / kg
45
40
35
Reference
30
25
2500 3000 3500 4000 4500 5000 5500 6000
Meters
:
11.6. (a and b) Published mean V O2max values for developmentally acclimatized males living at
altitude i.e., long-term European residents of Colorado and the Andes, and Han Chinese migrants
to the Tibetan plateau. Mean values are superimposed on the sea-level native reference data (from
Figure 11.2) across the altitude range from 3000–5500 meters. NS ¼ nonsignificant for a :test of
the hypothesis that developmentally acclimatized males have higher altitude specific V O2max
compared to lowland native males (sea-level reference) using regression analysis.
~50 years and they are superimposed on the mean lowland ancestry who were born and raised at altitude.
values for acclimatized lowland-native males (sea-level The latter include populations of European ancestry
reference) that were shown previously in Figure 11.2. living in Colorado and South America, and also popu-
Andean values across the range of altitude from 3000 lations of Han Chinese ancestry living on the Tibetan
to 5500 m are clearly and significantly above the sea- plateau. Therefore, a cautious interpretation of these
level reference line (P ¼ 0.002). Unfortunately, statis- results (given the small sample of studies) is that genes
tical power is insufficient to test this hypothesis inde- play a more important role than developmental adap-
:
pendently with natives from the Himalayas. In tation in determining the high the V O2max of Andeans
contrast, in a similar analysis, Figure 11.6 reveals no and Himalayans. Unfortunately, confounding factors
:
difference in mean V O2max values for populations of cannot be excluded, particularly the high physical
activity levels that are common among highland native et al., 1967; Kayser et al., 1994). One additional study
groups (Kashiwazaki et al., 1995; Brutsaert, 1997). reported higher WE in Tibetans resident at 4440 m
Confounding is a difficult issue to resolve and versus Tibetans resident at 3658 m (Curran et al.,
limits the inference of genetic adaptation based on 1998). Studies from Colorado show no differences in
group differences using the comparative approach. WE related to acclimatization state or growth and
This may perhaps explain the conflicting conclusions development at altitude (Dill et al., 1931; Balke, 1964;
reached by different investigators and different stud- Grover et al., 1967). For economy, two recent studies
ies. One previous study in the Andes argued for a gen- have reported a lower O2 cost for treadmill running
:
etic basis to explain the high V O2max of Aymara after (Bastien et al., 2005; Marconi et al., 2005) or load
controlling for physical activity level (Frisancho et al., carrying (Bastien et al., 2005) in Sherpa. Both studies
1995), while at least three others studies emphasized are difficult to interpret with respect to metabolic effi-
developmental and/or covariate effects (Greksa and ciency given differences in body size between study
Haas, 1982; Greksa et al., 1985; Brutsaert et al., groups, and in the case of the Bastien et al. (2005)
1999b). A recent study by Brutsaert and colleagues study, differences in study location. Thus, on balance,
(2003) argued for a genetic basis based on a negative there is little compelling evidence to support the
:
correlation between DV O2max and the proportion of hypothesis that altitude natives use O2 more efficiently
Native American ancestry in a sample of 32 lowland in the performance of physical work.
males of mixed Quechua-European ancestry who were
transiently exposed to hypoxia. While admixture-based
studies allow stronger inference regarding the action of Endurance performance
genes, the problem of confounding remains. Thus, Hurtado’s aforementioned classic study is the only
resolution of this issue will require a more direct report in the literature where a true endurance out-
interrogation of the genetic basis of human perfor- come was measured, i.e., time to exhaustion during a
mance at altitude (see Sections VII and VIII) and/or a sustained bout of submaximal work. Hurtado reported
better understanding of how developmental exposure a higher average tolerance time for treadmill running
impacts oxygen transport capacity. in 10 altitude natives of Morococha, Peru (4540 m)
versus 10 sea-level residents of Lima, Peru (34.2 versus
Work efficiency and the economy of locomotion 59.4 minutes). The difference was impressive as each
group was tested in their native environment! How-
Work efficiency (WE) is defined as the ratio of exter- ever, without information on subject fitness status
nal work (output) to metabolic cost (input), with exter- and on the performance of both groups in the same
nal work typically measured on a treadmill or cycle environment, the study is also difficult to interpret.
ergometer and metabolic cost typically measured
as O2 cost, i.e., O2 consumption (VO2). Economy is a
related but different construct, defined as the O2 cost Summary of work capacity studies
for a specific activity, like load carrying or running. In
both cases, the evolutionary advantage of using O2 Numerous studies of indigenous altitude natives dating
efficiently to do work in an O2 poor environment is back nearly half a century reveal higher than expected
:
self-evident, particularly considering the agricultural values of V O2max at a given altitude, but the genetic
and pastoral labor demands that characterize life in versus environmental origins of this difference remain
the Andes (Kashiwazaki et al., 1995) and also on the obscure. Regarding energetic advantage during work
Tibetan plateau. Alberto Hurtado, in his pioneering or exercise, there is widespread conflict in the litera-
studies in Peru was the first to suggest that altitude ture and no firm conclusions are possible. Regarding
natives have a higher metabolic WE (Hurtado, 1932, endurance capacity, this aspect of work performance
1964). The subsequent literature in support of this has yet to be thoroughly evaluated.
hypothesis is conflicted. Several studies have reported
higher WEs in Andeans versus lowland controls
(Reynafarje and Velasquez, 1966; Haas et al., 1983; SECTION V: DO HIGH-ALTITUDE NATIVES
Hochachka et al., 1991), while other studies have HAVE ENHANCED REPRODUCTIVE
shown no differences (Mazess, 1969a, 1969b; Brutsaert PERFORMANCE AT HIGH ALTITUDE?
et al., 2004), or indeed lower WE in Andeans (Kollias
et al., 1968). Two studies have reported significantly Reproductive performance is central for any species.
higher WE in Tibetans versus lowland controls at In this section, measures of reproductive success are
altitude (Ge et al., 1994b; Niu et al., 1995), while three considered, including fertility, fecundity, prenatal and
other studies have reported no WE differences in postnatal mortality, birthweight, and various measures
Sherpas or Tibetans (Lahiri and Milledge, 1966; Lahiri of maternal O2 transport to the fetus.
Fertility and fecundity as selective agent on the locus for SaO2 by the mechanism
of higher infant survival of Tibetan women with high
As cited by Carlos Monge (1948), sixteenth-century
SaO2 genotypes. These results are also consistent with
Spanish historians were the first to note fertility/
the physiological studies described below that suggest a
fecundity impairments in Spanish women who settled
pathway linking maternal O2 delivery, fetal growth, birth-
in the Andean highlands. Monge proposed that hypobaric
weight, and the probability of infant survival.
hypoxia lowers fertility, either by increasing fetal wastage
or pregnancy loss (i.e., prenatal mortality), and/or by
Birthweight
decreasing the ability of a woman to conceive (fecundity).
These hypotheses are difficult to test in humans given Birthweight has long been an important outcome
myriad cultural and behavioral influences on fertility, to assess reproductive performance at altitude.
and given the difficulty of directly assessing prenatal Figure 11.7 shows the birthweight decrement with hyp-
mortality or fecundity. However, the animal literature oxia (Dbirthweight), estimated to be about 100 g per
does give some evidence of reduced fertility/fecundity 1000 m. Long-term resident populations appear to be
attributable to hypoxia when lowland native rats are buffered from the normal Dbirthweight, reminiscent of
:
raised in hypoxic conditions (Martin and Costa, 1992). pattern observed for DV O2max (see Figure 11.5). Speci-
In this context, what emerges as noteworthy is the appar- fically, on the basis of worldwide birthweight data,
ently “normal” fertility and fecundity of indigenous high- Moore and colleagues have argued that Dbirthweight
land populations in both the Andes and the Himalayas. as a consequence of hypoxia varies according to
Although there is substantial interpopulation variability the duration of population exposure to hypoxia
in fertility within altitude regions, the ranges observed (Niermeyer et al., 2001; Moore, 2003; Julian et al.,
are similar to those for natural fertility sea-level popula- 2007). Populations with the shortest history at altitude,
tions. Considering fecundity alone, only one study has such as North Americans in Colorado or Han Chinese
intensively investigated this issue in an indigenous migrants to the Tibetan plateau, experience the
altitude group, with no evidence that the probability of greatest Dbirthweight. Populations with the longest
conception was reduced in Andean Aymara women exposure (i.e., ancestral exposure), such as Tibetans
(Vitzthum and Wiley, 2003). and Andeans, experience more modest Dbirthweight.
Notably, altitude-specific birthweight is higher in indi-
genous populations compared to lowland controls
Prenatal and postnatal mortality despite socioeconomic differences that might other-
wise predict lower birthweight. For example, Haas
Prenatal, neonatal (birth to 28 days), and infant (birth to
et al. (1980) found higher birthweight among Aymara
1 year) mortality rates are generally high in highland
women compared to European controls in Bolivia,
populations, but this is not unexpected given the signifi-
despite the fact that the European women had better
cant levels of poverty in most mountainous areas of the
access to health care and better nutrition. Recently, a
world. However, hypoxia may also have a direct effect.
study by Bennet et al. (2008) provided evidence that
Consider that in Colorado, until the 1980s, high-altitude
genetic factors are involved to explain the higher birth-
regions had higher neonatal and infant mortalities rates
weight of Andeans. Using an admixture approach
compared to lowland regions (Moore, 2003). Lowland
based on surname analysis, this study shows a direct
migrants to altitude may have a higher mortality risk than
association of indigenous high-altitude ancestry with
indigenous altitude groups. Moore (2003) reported three-
protection against hypoxia-associated fetal growth
fold higher prenatal mortality and higher neonatal and
reduction in a cohort of 1343 singleton births in La
infant mortality rates in Chinese migrants to the Tibetan
Paz, Bolivia.
plateau compared to Tibetan natives. Quantitative gen-
Whether there are differences in altitude-specific
etic studies by Beall et al. (2004) in Tibetans suggested
mean birthweights between Andeans and Tibetans is
that there may be genetic factors at work to explain these
unclear. Moore (2000) has argued that Tibetans have
mortality-risk differences. In an original series of studies,
higher mean birthweight compared to Andeans, but
these investigators measured resting SaO2 within fam-
Beall (2000) have argued against this population differ-
ilies. A significant proportion of the age- and sex-adjusted
ence and suggest that women from both populations
variance (from 21% to 39%) was attributed to additive
are equally effective at supporting fetal development as
genetic factors with the overall pattern of variance best
measured by birthweight.
explained by a major gene conferring a 5–6% point
increase in resting SaO2 (Beall et al., 1997a, 1997b). In a
The placenta
follow-up study, Tibetan women with a high likelihood of
possessing one to two of the putative alleles for the high How do indigenous altitude native women produce
SaO2 phenotype had more surviving children (Beall et al., larger babies? One structural parameter to consider is
2004). This study provides evidence that hypoxia is acting the placenta which undergoes significant growth and
∆ Birthweight with increasing altitude

3800
3600
Tibetan
3400
Birthweight (g)
Tibetan
3200
3000
2800
2600
0 1000 2000 3000 4000 5000
Altitude (m)
11.7. Mean birthweights by altitude from previously published studies of altitude residents from
North and South American and the Tibetan plateau. Figure is from Moore et al., (2001). On average,
birthweight (BW) decreases with altitude, approximately 100 grams per 1000 meters. See text for a
discussion of group differences.
remodeling during pregnancy to optimize gas and generations of altitude ancestry, but falls during preg-
nutrient exchange between the maternal and fetal cir- nancy in residents with less than three-generations
culations. At altitude, it has consistently been observed exposure. This suggests that developmental effects
that placentas are more vascularized, i.e., a higher accumulate across generations (i.e., maternal effects)
density of blood vessels, perhaps to compensate for affecting O2 delivery to the fetus.
lower uteroplacental blood flow at altitude. There are To emphasize the importance CaO2 on birthweight,
other structural changes in the high-altitude placenta, consider the studies of Moore and colleagues con-
but without going into detail, these generally operate ducted in Colorado, Peru, and the Himalayas (reviewed
to increase the diffusion capacity of this tissue. These in Moore, 2003). These researchers have shown that
changes are evident to some degree in both recent larger birthweight babies are born to mothers who
migrant- and native-altitude populations, and so it is show higher VE, greater increases in hypoxic ventila-
not clear whether changes in placental architecture tory sensitivity during pregnancy, and higher CaO2
per se can account for the larger birthweight babies during pregnancy. However, these are within group
of Tibetans and Andeans. Indeed, only a few studies effects only, and CaO2 differences per se probably do
have directly compared placental morphology between not explain the birthweight differences between
highland native and lowland groups, and these have groups. For example, in one study, Tibetan women
offered conflicting results (Zamudio, 2003). had lower pregnancy [Hb] than Han Chinese, and thus
lower pregnancy CaO2. Despite lower CaO2, Tibetan
women produced babies nearly 0.5 kg heavier than
Maternal O2 transport
Chinese residents at ~3600 m. This paradox led Moore
Another possibility to increase birthweight is enhanced and colleagues to consider the role of uteroplacental
maternal O2 transport to the uteroplacental circula- blood flow in determining birthweight, recalling that
tion. Under normal conditions, maternal VE increases O2 delivery (not CaO2) is the important functional par-
during pregnancy as mediated by several reproductive ameter depending on both CaO2 and blood flow (Moore
hormones, but principally progesterone. Increased VE et al., 2001). Uterine artery blood flow velocity was
serves to increase SaO2, and this process could be higher in Tibetans, presumably increasing O2 delivery
especially important at altitude considering that CaO2 to the uteroplacental circulation. The latter may be the
may actually fall due to an expansion of blood volume simple result of structural adaptation, i.e., an enlarge-
during pregnancy without a concomitant expansion of ment in the diameter of the uterine artery permitting
the red blood cell mass, i.e., a kind of “anemia of higher blood flow. Additional data consistent with this
pregnancy.” Interestingly, McAuliffe et al. (2001) have hypothesis are now emerging from the Andes. Com-
shown that CaO2 is stable during pregnancy in resi- pared to women of European ancestry resident at
dents of Cerro de Pasco, Peru, with three or more 3600 m, Andean women have greater uterine artery
enlargement during pregnancy, increased uterine Secondly, some traits differ in interesting ways
artery blood flow at week 36 of pregnancy, and thus a between highland native groups in the Andes, the
1.6-fold greater uteroplacental O2 delivery near term Himalayas, and other regions. This means that there
(Wilson et al., 2007). Unfortunately, comparisons have may be different patterns of adaptation in each region,
not yet been made with women of either Han Chinese offering different solutions to the same environmental
or European ancestry who were born and raised at problem of hypobaric hypoxia (Moore et al., 1992;
altitude. Thus, at present, little is known regarding Beall, 2000).
the developmental and/or evolutionary origins of this
structural change. Further, there are other poorly
Resting ventilation
understood differences between highland populations
in the physiological response to pregnancy. For A study by Chiodi et al. (1957) in the Andes was the
example, Andean women have relatively high [Hb] first to measure the relative resting VA in a high-
and CaO2 during pregnancy compared to Tibetan altitude native group. Compared to acclimatized
women. Andean women also have a different pattern lowland controls, lifelong residents of the Andean alti-
of breathing during pregnancy to increase VE com- plano at 3990–4515 m showed lower “effective VA” at
pared to European women (Vargas et al., 2007). rest. A full description of the concept of effective VA is
beyond the scope of this chapter, but functionally, low
effective VA implies lower ventilation (hypoventilation)
Summary of reproductive performance studies
to maintain a given value of the PaO2. The basic find-
Most of the evidence in support of a fertility and/or ing of a relative hypoventilation in Andeans has been
mortality advantage among indigenous altitude groups repeatedly confirmed (Hurtado, 1964; Severinghaus
is anecdotal. However, indigenous highland women et al., 1966; Lahiri, 1968; Cudkowicz et al., 1972; Beall
clearly give birth to larger babies at altitude compared et al., 1997a; Moore, 2000), but has not generally been
to lowland women. Generally, this is related to one or replicated in Tibetans or described in populations with
more mechanisms that operate to increase nutrient lifelong developmental exposure to hypoxia (Weil et al.,
and oxygen flow across the placenta. Like the high 1971; Moore, 2000). Thus, Andeans may be unique in
exercise capacity of the indigenous altitude native, the showing a relative hypoventilation at rest in hypoxia,
developmental versus genetic origins of this difference while Tibetans and developmentally exposed popu-
are obscure. However, recent studies do provide some lations may have a “normal” resting VA not different
evidence that genetic factors are at work affecting from the VA of lowlanders after ventilatory acclimatiza-
various aspects of reproductive performance, both in tion to hypoxia (Zhuang et al., 1993). The functional
Andean and Tibetan women (Beall et al., 2004; Bennet significance of differences in alveolar ventilation
et al., 2008). between populations is not known. One possibility
for the Andean–Tibetan difference is that it relates to
or explains the higher prevalence of chronic mountain
SECTION VI: SPECIFIC STRUCTURAL AND sickness in the Andes, as suggested by Moore et al.
FUNCTIONAL TRAITS OF THE O 2 TRANSPORT (1998).
SYSTEM
Ventilatory control and chemosensitivity

The focus of this section is on specific traits related to
the O2 transport system, rather than on broader adap- The low VE and VA in Andeans may have something
tive domains like exercise or reproductive capacity. to do with the ventilatory control system, which (as
Following the organization of the O2 transport system described previously) is both centrally and peripherally
itself, the section begins at the lung with a consider- mediated by the brain respiratory center and carotid/
ation of VE and then moves down the O2 transport aortic chemoreceptors, respectively. The earliest stud-
chain terminating at the muscle-metabolic level. ies of ventilatory control were conducted at about
A priori, two points are worth considering. Firstly, the same time in the Andes, Colorado, and the
not all of the specific trait differences that are dis- Himalayas beginning in the late 1960s. In the Andes,
cussed below have obvious adaptive benefits. For a number of studies showed lower sensitivity of che-
example, high average [Hb] characterizes many popu- moreceptors (i.e., lower chemosensitivity) to hypoxia
lations at high altitude. While increased [Hb] certainly or a lower ventilatory response to hypoxia, with the
increases CaO2, elevated red blood cell levels also latter termed the HVR, or the hypoxic ventilatory
increases blood viscosity which increases the work response (Severinghaus et al., 1966; Sorensen and
(afterload) on the heart. Thus, some investigators have Severinghaus, 1968b; Cudkowicz et al., 1972). In the
argued that increases in [Hb] at altitude constitute a Himalayas, early studies also suggested a lower HVR in
maladaptive response (Winslow et al., 1985, 1989). Sherpas (Lahiri et al., 1967; Lahiri, 1968). Meanwhile,
in Colorado, studies of Leadville residents also showed of gas-exchange limitation, including diffusion limi-
“blunted” chemosensitivity, with the implication being tation (Dempsey et al., 1995). Against this background,
that blunting was acquired from lifelong exposure to it is noteworthy that many exercise studies conducted
hypobaric hypoxia (Forster et al., 1971; Weil et al., at altitude report lower absolute VE (L/min) and/or
1971; Byrne-Quinn et al., 1972). Thus, for a time there lower VE relative to metabolic oxygen consumption
was apparent consensus in the literature that long- (VE/VO2) in highland natives compared to lowland
term hypoxic exposure resulted in desensitization of controls. These include one study of exercise in a
the ventilatory control system, and also that this was Colorado group born and raised at altitude (Dempsey
a universal human phenomenon that could explain et al., 1971), nearly all studies in the Andes (Kollias
the blunted chemosensitivity of disparate high-altitude et al., 1968; Schoene et al., 1990; Brutsaert et al.,
groups worldwide. However, since the 1970s, additi- 2000; Wagner et al., 2002), and most (Lahiri and
onal studies have complicated this view somewhat. Milledge, 1966; Lahiri et al., 1967; Dua and Sen Gupta,
While Andean studies are nearly uniform in 1980; Ge et al., 1994b; Zhuang et al., 1996) but not all
showing a blunted chemosensitivity among Aymara/ (Sun et al., 1990a) studies in the Himalayas. It is not
Quechua (Chiodi, 1957; Severinghaus et al., 1966; clear whether these are developmental or genetic
Sorensen and Severinghaus, 1968a; Lahiri et al., 1969; effects. However, in support of the genetic hypothesis,
Cudkowicz et al., 1972; Leon-Velarde et al., 1996; Beall one study by Brutsaert et al. (2005) shows a strong
et al., 1997a; Moore, 2000; Gamboa et al., 2003; negative association of Quechua ancestry proportion
Brutsaert et al., 2005), in the Himalayas a different with VE and VE/VO2 in lowland-born subjects tested at
pattern seems evident. Most (Hackett et al., 1980; 4338 m. This finding is consistent with better gas
Huang et al., 1984; Zhuang et al., 1993; Ge et al., exchange in Quechua. For example, higher diffusion
1994a; Beall et al., 1997a) but not all (Santolaya et al., capacity or gas exchange efficiency could in theory
1989) studies of Tibetans and Sherpa since the late allow more O2 to enter the blood for the same or lower
1960s have shown a normal HVR and high or normal level of VE. Indirectly, measures of increased pulmon-
resting VE despite lifelong exposure to hypoxia. There ary volume and/or increased diffusion capacity in
is indirect evidence to support the idea that these highland natives (see below) also supports the idea
traits are genetically determined in both Andean and that lower exercise VE is made possible by better gas
Himalayan populations. For example, a study by exchange. However, lower exercise VE could also
Curran et al. (1997) showed lower HVR in admixed reflect a difference in ventilatory control that is inde-
Chinese-Tibetans (Chinese fathers and Tibetan mothers) pendent of gas exchange.
compared to nonadmixed Tibetans despite similar
resting VE between groups. In the Chinese admixed group
Pulmonary volumes
only, HVR decreased with duration of altitude residence,
suggesting that full Tibetan ancestry protected against Nearly all highland populations studied thus far have
hypoxic desensitization. In the Andes, Brutsaert et al. larger mean pulmonary volumes compared to sea-level
(2005) showed a strong negative association of HVR with controls, including total lung volume, vital capacity,
the proportion of Native American ancestry, the latter and the residual volume. This includes both develop-
assessed using a panel of 81 ancestry informative mole- mentally exposed populations and indigenous groups
cular markers. Finally, a study by Beall et al. (1997a) (Sun et al., 1990a; Frisancho et al., 1997; Brutsaert
conducted at the same time in both the Andes and the et al., 1999a). From studies of developmentally exposed
Himalayas, could find no evidence of acquired blunting populations, as well as from numerous animal studies
in either indigenous population, i.e., HVR did not (Johnson et al., 1985), it is clear that much of this effect
decrease with age over time, at least from adolescence is explained by lung growth during infant/child devel-
onward. However, in this study Andean HVR was clearly opment in response to lifelong hypoxia. For example,
lower than Tibetan HVR. Figure 11.8 is a comparison of lung volumes between
two groups of Peruvian women who were matched for
ancestry (i.e., genetics) but who differed by where they
VE during exercise
were born and raised (Lima, at sea-level, versus Cerro
At the onset of exercise, VE increases commensurate de Pasco at 4338 m). Cerro de Pasco women had ~15%
to meet gas exchange requirements and metabolic larger total lung volume compared to Lima women.
demand. At altitude compared to sea-level, VE (L/min) Whether “bigger is better” remains controversial, but
is higher for a given level of fixed work, depending on at least one study in the Himalayas reported a positive
:
the specific altitude, and this is true for nonnatives and correlation between forced vital capacity and V O2max
natives alike (Brutsaert et al., 2003; Marconi et al., (Sun et al., 1990a). A similar study in the Andes failed
2004). Further, in lowland natives, depending on the to find this association within study groups (Brutsaert
severity of exercise and altitude, there is clear evidence et al., 1999b, 2000).
Pulmonary volumes
Born and raised at sea-level Born and raised >4000 m
6000
P<0.01
5000
P<0.01
4000
ml-BTPS
3000
2000
P<0.01
1000
0
Residual volume Forced vital capacity Total lung volume
11.8. Pulmonary volumes are larger in Peruvian women who were born and raised above 4000
meters, compared to women born and raised at sea-level. Note: women in each group were matched
on genetic background using a panel of ancestry informative molecular markers (see Brutsaert et al.,
2003). BTPS refers to body temperature, pressure, and saturation.
Arterial O2 saturation (SaO2) et al., 1995). Secondly, the quantitative genetic studies
already described in detail (see Section V), suggest a
Numerous comparative studies show higher SaO2s at
major gene with a substantial phenotypic effect on
rest and during submaximal and/or maximal exercise
resting SaO2 (Beall et al., 1997a, 1997b). Finally, there
in indigenous high-altitude native populations (Sun
is little evidence that SaO2 is higher with developme-
et al., 1990a; Ge et al., 1994b, 1995; Favier et al., 1995;
ntal adaptation to altitude. In the few studies of deve-
Zhuang et al., 1996; Chen et al., 1997; Brutsaert et al.,
lopmentally exposed groups, SaO2s were similar
2000). It is important to note that these studies meas-
between acclimatized lowlanders and Europeans born
ured SaO2 via pulse oximetry. Pulse oximetry is a non-
and raised at altitude during submaximal exercise
invasive technique that correlates well with direct
(Dempsey et al., 1971; Brutsaert et al., 2000) and at
measures on whole blood, but there may be problems :
V O2max (Frisancho et al., 1995). A recent study from
with bias particularly during intense exercise (Yamaya
Qinghai China reports no differences in resting SaO2
et al., 2002). In the Andes, there is some conflict in the
between large cohorts of Tibetans and Han Chinese
literature. Compared to fully acclimatized lowlanders,
who were both born and raised at altitude (Weitz and
two studies show no difference in Aymara submaximal
Garruto, 2007), although whether this is also the case
and maximal exercise SaO2, one study shows compar-
for exercise SaO2 cannot be determined from the
able SaO2s despite lower VE in Aymara (Schoene et al.,
resting data alone.
1990), and three studies show higher SaO2s during
submaximal (Favier et al., 1995; Brutsaert et al.,
2000) and/or maximal exercise (Frisancho et al.,
Blood gases and direct measures of pulmonary
1995). Two of these studies showed higher exercise
gas exchange
SaO2s in Aymara even when compared to Europeans
who had been born and raised at 3600 m, suggesting a A handful of studies have measured arterial gas partial
genetic effect (Favier et al., 1995; Brutsaert et al., pressures at rest or during exercise in highland natives,
2000). In the Himalayas, nearly all studies show higher and these have been very informative. In particular,
exercise SaO2s at altitude in Tibetans or Sherpas com- evaluation of blood gases during exercise is useful
pared to acclimatized lowland controls (Sun et al., given the additional demands placed on the pulmonary
1990a; Ge et al., 1994b, 1995; Zhuang et al., 1996; Chen gas exchange system compared to rest. An early classic
et al., 1997). Studies of resting SaO2 in Tibetans indir- study by Dempsey et al. (1971) compared sojourners
ectly support a genetic basis for the high exercise with residents of Leadville, Colorado at 3094 m.
SaO2s. Firstly, Tibetan-native neonates born at altitude Colorado natives had smaller (A-a)DO2 especially as
have higher resting SaO2s compared to neonates exercise intensity increased. Recall that smaller (A-a)
born to acclimatized lowland mothers (Niermeyer DO2 can mean a better efficiency of gas exchange.
Thus, from the Colorado work, it may be inferred that resistance of local capillary networks and the venous
differences in (A-a)DO2 between altitude natives and return of blood to the heart. Notwithstanding the sig-
lowland controls are due at least in part to developmen- nificant hemodynamic changes that occur with alti-
tal adaptation to high altitude. However, this does not tude exposure and acclimatization (not discussed
preclude the possibility of genetic effects. Zhuang et al. here), there is little to suggest that altitude natives
(1996) showed that Tibetans had lower VE and about differ with respect to cardiac output, although data
half the (A-a)DO2 compared with acclimatized Han Chi- are limited. One report suggests the possibility of
nese at 3658 m, again with the (A-a)DO2 increasing higher stroke volume and lower peripheral resistance
between groups as VO2 or power output increased. in Tibetans (Groves et al., 1993), but most reports from
A recent study by Lundby et al. (2004) at 4100 m showed the Andes indicate normal Q at rest and during exer-
remarkably low (A-a)DO2 (1–2 mmHg) at rest and cise (Banchero and Cruz, 1970; McKenzie et al., 1991),
during exercise to maximum in Aymara compared to or indeed lower Q in residents of Cerro de Pasco, Peru
Europeans with 8 weeks of acclimatization. A study by (Vogel et al., 1974). In the terminal step of O2 trans-
Wagner et al. (2002), at the relatively extreme altitude of port, oxygen must diffuse into working muscle, and a
5260 m, also showed that Aymara natives have mark- greater O2 extraction at this level could obviate any
edly lower VE and lower (A-a)DO2, especially as exercise need to increase Q. From limited data, Niermeyer and
intensity increased. Improved gas exchange efficiency colleagues (2001) reported no differences in O2 extrac-
may have a simple structural basis in larger pulmonary tion between Andeans, Tibetans, and Colorado altitude
volumes. Wagner et al. (2002) calculated that the O2 natives, but at least one recent report showed parado-
:
diffusing capacity during maximal exercise was 40% xically lower O2 extraction at V O2max in Andeans com-
higher in Aymara compared to acclimatized pared to acclimatized lowland controls (Lundby et al.,
Europeans, and many other studies document higher 2006). The few studies in this area are potentially con-
diffusion capacities of highland natives at rest founded by subject fitness status, which greatly affects
(Remmers and Mithoefer, 1969; Vincent et al., 1978). stroke volume and other aspects of the hemodynamic
response to exercise. Thus, more work is necessary
before firm conclusions may be drawn.
The cardiovascular system
One final trait considered in this section is exhaled
At the heart structural level, a small number of studies pulmonary nitric oxide (NO), which may have some
suggest changes in cardiovascular growth patterns relevance to blood flow, both in the lung and at the
at altitude, but there is no convincing evidence of systemic level. Beall and colleagues reported high
meaningful population differences (Penaloza et al., values of exhaled NO in both Andean and Tibetan
1963; Hulme et al., 2003). In persons born and raised populations compared to sea-level standards (Beall
at altitude, there tends to be a relative enlargement of et al., 2001; Hoit et al., 2005). Nitric oxide is a power
the right ventricle, i.e., predominance. This is expected vasodilator that regulates blood vessel diameter and
as hypoxia provokes a vasoconstriction of the pul- local blood flow. Interestingly, Tibetans had nearly
monary vasculature with a concomitant increase in twice the mean exhaled NO of Andeans. Also, in
pulmonary artery pressure (PAP). Presumably Tibetans higher exhaled NO was associated with
increased PAP is an adaptive response, perhaps serving higher pulmonary blood flow. These authors suggest
to deliver a more uniform blood flow to the upper lung. a beneficial role of NO in Tibetans allowing for higher
On the other hand, persistent pulmonary hypertension pulmonary blood flow and O2 delivery without the
is also associated with some of the acute and chronic consequences of higher PAP.
problems of hypoxic exposure, including pulmonary
edema and chronic mountain sickness. In this context,
Hemoglobin-O2 affinity
what is most interesting is the absence of pulmonary
hypertension in many altitude-adapted species like the Certain altitude-adapted species have high Hb-O2
llama (Heath et al., 1974), and the very low prevalence affinity, attributable to amino acid sequence variation
of pulmonary hypertension in Tibetans (Groves et al., in the hemoglobin molecule itself (Black and Tenney,
1993). This is in some contrast with Andean groups 1980). However, this does not appear to be the case for
and Han Chinese migrants to the Tibetan plateau human groups adapted to altitude. For both Andeans
who have higher prevalence of pulmonary hyperten- and Tibetans, Hb-O2 affinity is similar to that of low-
sion and chronic mountain sickness (Sun et al., land groups as assessed on whole blood by the position
1990b; Niermeyer et al., 2001). of the Hb-O2 dissociation curve (Samaja et al., 1979;
At the heart functional level, cardiac output (Q) Winslow et al., 1981). Further, at this time, there are
increases to match O2 delivery to metabolic demand. no reports of hemoglobin genetic variants unique to
Q is regulated by increases in the heart rate or stroke altitude native populations. Similarly, for myoglobin,
volume, and is also affected by the peripheral the muscle analog of hemoglobin, analysis of one
exon in Tibetans does not show any novel polymorph- more work is needed in this area to replicate previous
ism or selection for specific myoglobin alleles (Moore findings and special attention should be given to
et al., 2002). matching comparison groups on physical activity
levels. Finally, there is no evidence that muscle fiber-
type distributions are different in altitude natives,
Hemoglobin concentration [Hb]
although again only two studies have addressed this
A number of large-scale surveys now make it clear that question, one each in the Andes and in the Himalayas
Tibetan populations have lower [Hb] compared to (Desplanches et al., 1996; Kayser et al., 1996).
Andean, European, or Han Chinese populations resi- At the muscle metabolic level, Hochachka et al.
dent at altitude (Beall et al., 1998; Moore et al., 2002; (1991) reported a persistent “lactate paradox” in
Garruto et al., 2003; Wu et al., 2005). Indeed, Tibetan Andeans transported and tested at sea-level. The lactate
values at moderate altitude are not largely different paradox refers to the observation that arterial lactate
from sea-level values, a paradoxical finding given the levels at a given level of work tend to be higher during
expected [Hb] increase with acclimatization. Hemo- exercise on acute exposure to hypoxia, but then return
globin production is regulated by the hormone to near sea-level values after acclimatization time,
erythropoietin, which is upregulated by hypoxemia. despite continued hypoxia. Hochachka et al. (1991)
The low [Hb] in Tibetans suggests the absence of an reported persistently low lactate levels in Andeans even
hypoxic stimulus to increase erythropoietin, but how after six weeks at sea-level, and suggested this was part
exactly this comes about is unknown. Also interesting of a fundamental metabolic reorganization (i.e., adap-
is the emergent evidence from Ethiopia. A recent study tation) on the part of the altitude native subjects.
of 236 Ethiopian native altitude residents by Beall et al. According to Hochachka and colleagues, Andeans favor
(2002) shows low [Hb], also within the ranges of sea- carbohydrate oxidation because glucose (glycogen)
level populations. For myoglobin, one study by Gelfi metabolism uses O2 efficiently. The low lactate levels
et al. (2004) shows an upregulation of the myoglobin may be a reflection of a tight coupling between carbo-
protein in Tibetans compared to lowland Nepali control hydrate-based ATP synthesis and efficient pathways for
subjects. However, the genetic, developmental, and/or ATP utilization. This hypothesis has yet to be confirmed
environmental basis of this trait difference is unknown. and is at some variance with the recent study of Wagner
et al. (2002) who showed similar lactate levels in
Andeans and lowland controls at altitude. However,
Muscle structure and metabolism
these authors did report an increased lactate acid buf-
An early study in the Andes reported increased muscle fering capacity in Andeans compared to acclimatized
myoglobin and oxidative enzyme concentration in lowlanders on the basis of measured bicarbonate
Quechua compared to lowland controls (Reynafarje, levels during exercise. In the Himalayas only a few stud-
1962). However, this study has been criticized on the ies have measured lactate levels. During exercise at
basis of training differences between the two compari- 4700 m, Ge et al. (1994b) showed lower lactate levels,
son groups (Saltin et al., 1980), and subsequent studies before and at the end of exercise, in Tibetans-versus-
have not replicated the findings. Indeed, prolonged acclimatized Han Chinese. Two studies conducted
exposure to hypoxia in lowlanders tends to decrease in Kathmandu, Nepal (1300 m), show similar (Kayser
muscle oxidative capacity in both relative and absolute et al., 1994) or lower (Marconi et al., 2005) lactate levels
terms, i.e., decreased mitochondrial volume density in Tibetans-versus-Nepali control populations. Unfor-
and muscle mass. Hypoxia also decreases the activity tunately, the lactate response is highly dependent on
of several key oxidative enzymes (Green et al., 1989; subject fitness status and acclimatization state, and so
Hoppeler et al., 1990; Howald et al., 1990). Altitude studies conducted thus far are difficult to interpret
natives from both the Andes and the Himalayas appear regarding adaptive metabolic differences in lactate
similar in this regard showing lower mitochondrial production/elimination in high-altitude natives.
volume densities and/or oxidative enzyme activities
(Kayser et al., 1991, 1996; Desplanches et al., 1996;
Hoppeler et al., 2003). Further, in Andeans the SECTION VII: GENES AND ALTITUDE
muscle-training response is similar to that seen in low- ADAPTATION
landers, including increases in capillary-to-fiber ratio,
capillary density, the volume density of total mitochon- At the beginning of this chapter it was stated that no
dria, and the activity of citrate synthase (Desplanches direct (genetic) evidence exists to support the hypoth-
et al., 1996). Interestingly, Kayser et al. (1996) report esis of natural selection in response to hypobaric hyp-
lower mitochondrial volume density even in Tibetan oxia in a human population. What support exists for
migrants born at moderate altitude (1300 m), suggest- this hypothesis is by inference from trait differences
ing that this may be a fixed genetic trait. However, between populations. Even the most directly
comparative studies fall short of providing specific Bigham et al., 2008). In most European populations,
information on a genetic system that may have been I-allele frequency is decidedly lower, ranging from
modified by natural selection in an altitude native ~0.15–0.55. Does this mean that the ACE I allele is an
group. However, there is a growing library of candidate “altitude gene” that was driven to relatively high
genes that are associated with the altitude response, frequency by natural selection? The problem with this
and these may have relevance to the larger question of conclusion, as Rupert et al. (1999) first noted for
human adaptation. Quechua, is that many other populations worldwide
Rupert and Koehle (2006) recently reviewed the show comparable or higher I-allele frequency without
literature on genetic associations with altitude disease, a history of altitude exposure. For example, I-allele
and much of it was centered on just a few candidate frequency is greater than 0.80 in a number of Native
biochemical systems including polymorphisms in the American and Asian groups. Also, at a minimum, the
pathway synthesizing nitric oxide, polymorphisms in evolutionary inference would require some demons-
the renin-angiotensin system that regulates cardiovas- tration of I-allele benefit on fertility/mortality in the
cular homeostasis, and polymorphisms in the hypoxia population under consideration. A phenotypic effect,
inducible factor-1 (HIF-1) and erythropoiesis path- per se, is not always sufficient to make a compelling
ways. In a literature that currently numbers less than case for phenotypic benefit on population demography.
20 independent studies, about half of the candidate Indeed, Bigam et al. (2008) have shown a strong I-allele
genes tested against various altitude pathologies were effect determining higher resting and exercise SaO2 in
statistically significant, and some of these are the focus Peruvian Quechua (P ¼ 0.008). However, it is unclear
of on-going current research. whether this is a common (within group) phenotypic
One such genetic system, the insertion/deletion effect of the ACE I allele, or whether the ACE gene
polymorphism of the angiotensin-converting enzyme has significance between groups as a locus of past
(ACE), is considered here in some detail because it natural selection.
may prove to be paradigmatic of how gene-association
studies are incorporated into our understanding of
human adaptation to high altitude. The insertion (I) SECTION VIII: FUTURE RESEARCH
allele of the ACE gene is associated with lower tissue
ACE activity, whereas the deletion (D) allele is asso- There are certainly compelling physiological differ-
ciated with elevated serum ACE activity. In studies of ences between highland and lowland populations.
altitude performance, the major focus has been on the But, despite these differences, the hypothesis of natural
possible benefit of the I allele as lower circulating ACE selection cannot be adequately tested for a given trait
may attenuate the hypoxic pulmonary vasconstrictor until the genetic architecture of that trait is under-
response, attenuate pulmonary hypertension, and thus stood. Fortunately, the genomic information revolu-
protect against AMS and high altitude pulmonary tion has made it possible to interrogate the genetic
edema. There is some evidence in support of this basis of complex traits in new and powerful ways.
hypothesis. In case control studies, the I allele was Several approaches are currently being applied, includ-
over-represented in a cohort of elite British climbers, ing molecular studies of gene expression and genomic
and it has been associated with success in reaching approaches that seek to identify the association of spe-
the summit of Mt. Blanc (4807 m) (Woods and cific genes or genomic regions with traits of interest.
Montgomery, 2001; Tsianos et al., 2005). The I allele Genome-wide association (GWA) strategies have
has also been associated with higher SaO2 in relatively emerged as perhaps the most powerful and efficient
rapid but not slower ascents to 5000 m, and with a means to dissect the genetic basis of complex traits
greater ventilatory response to exercise in hypoxia (Risch and Merikangas, 1996; McCarthy et al., 2008),
(Woods et al., 2002; Patel et al., 2003). In contrast, at and the advent of high-density genotyping arrays has
least one study suggests an I-allele disadvantage at allowed a shift away from candidate gene studies.
altitude. A study of Kyrgyz highlanders revealed a Using GWA, there have been many recent successes
three-fold higher frequency of the I/I genotype in in the elucidation of genes involved in disease pro-
subjects with high altitude pulmonary hypertension cesses such as type II diabetes (Saxena et al., 2007;
(Aldashev et al., 2002). In addition, the highland Scott et al., 2007; Sladek et al., 2007; Unoki et al., 2008;
Kyrgyz had lower I-allele frequency (0.56, n ¼ 87) Yasuda et al., 2008), breast cancer (Easton et al.,
compared to a Bishkek lowland control group where 2007; Hunter et al., 2007; Stacey et al., 2007, 2008; ; Gold
the I-allele frequency was 0.65 (n ¼ 276). et al., 2008), and prostate cancer (Yeager et al., 2007;
In any case, at the population level Andean Gudmundsson et al., 2007, 2008; Eeles et al., 2008;
Quechua have relatively high I-allele frequency (~0.72), Thomas et al., 2008). Two key elements of these succe-
with Tibetans showing slightly lower frequency sses have been the collection of large sample sizes (i.e.,
(0.51–0.64) (Rupert et al., 1999; Gesang et al., 2002; thousands of individuals) with the consequent increase
in study power to detect loci of modest effect, and the differences support the idea of “different, but
exponential advances in genotyping technologies that equally effective patterns of adaptation to
have dramatically improved genome coverage. altitude”?
Genome-wide association has not yet been applied to 4. Why has birthweight been used so extensively to
the study of the physiology of a highland native group, gauge population adaptation to hypoxia? Is birth-
or to investigate any of the pathologies of high altitude, weight a better outcome variable in this regard
:
but several recent papers describe the potential utility of than V O2max?
whole-genome approaches in this regard (Moore et al., 5. Of all the complex traits discussed in this chapter,
2004; Shriver et al., 2006). which, in your opinion, provides the best evidence of
At the molecular level, there has been intensive genetic adaptation to high altitude in a native group?
focus on the aforementioned HIF system. When intra- 6. How important is developmental adaptation?
cellular O2 levels fall, the HIF system is activated and
HIF-1a works as a transcription factor to regulate cel-
lular oxygen homeostasis via down-stream effects on
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12 Skin Coloration
Nina G.Jablonski
Human skin is functionally hairless and exhibits a wide pigments because they have a great capacity to absorb
range of natural colors from the most deeply saturated visible light. Much of their evolutionary value derives
dark brown to pinkish off-white. Differences between from their abilities to absorb more high-energy forms of
people in skin color are readily perceived and have electromagnetic radiation including UVR and ionizing
been used as the basis for classifying people into radiation, and to neutralize the chemical by-products
groups referred to as races or race-color identities created when cells interact with these agents.
(Harris et al., 1993). The array of colors observed in Eumelanin is the dominant form of melanin found
the skin of modern humans is greater than that of any in human skin. In its concentrated form, eumelanin is
other single mammalian species, and is the product of intensely dark because it absorbs broadly in the spec-
natural selection (Jablonski and Chaplin, 2000), des- trum of visible light, but its protective effects on the
pite some arguments to the contrary (Blum, 1961; body are due to its abilities to absorb more energetic
Frost, 1988; Robins, 1991; Aoki, 2002). Skin pigmen- and potentially damaging UVR. Eumelanin is a highly
tation in humans evolved primarily to regulate the heterogeneous polymer consisting of 5,6-dihydroxyin-
amount of ultraviolet radiation (UVR) penetrating the dole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid
skin and, thus, modify its bioactive effects. (DHICA)-derived units bound to proteins (Prota,
Color is imparted to skin by a variety of different 1992b; Ito, 2003). Eumelanin polymers take on differ-
substances, which are visible to varying degrees in ent physical conformations and are intractably stable,
different people. The most important of these sub- even when bombarded by high-energy radiation or
stances is the pigment, melanin, which is produced in reactive oxygen species (free radicals) (Fox and Vevers,
specialized cells called melanocytes within the skin. In 1960; Chedekel, 1995; Kollias, 1995a; Pathak, 1995;
people with very pale skin, the skin gets most of its Sarna and Swartz, 1998; Meredith and Sarna, 2006).
color from the bluish-white connective tissue of the Ultraviolet radiation can break the chemical bonds that
dermis and from oxyhemoglobin and deoxyhemoglo- maintain the integrity of important molecules such as
bin associated with red blood cells circulating in the DNA and the constituents of cell membranes, causing a
capillaries of the dermis. The red color produced by toxic cascade of events that produces reactive oxygen
circulating hemoglobin becomes more obvious, espe- species (free radicals), which disrupt normal chemical
cially on the face, when the arterioles dilate and reactions in cells (Caldwell et al., 1998; Hitchcock,
become engorged with blood as a result of prolonged 2001; Cleaver and Crowley, 2002). Eumelanin absorbs
exercise or sympathetic nervous stimulation caused by and scatters ultraviolet and visible light, and works
embarrassment or anger (Jablonski, 2006). Variation chemically to prevent free radical formation and neu-
in human skin color is due primarily to its melanin tralize free radicals if they are formed (Mason et al.,
content, and so this chapter deals exclusively with the 1960; Meredith and Sarna, 2006). Eumelanin’s super-
properties and evolutionary significance of melanin. ior antioxidant properties work to great advantage
both in the skin and in the retina of the eye, where they
prevent and quench free radical damage caused by
MELANIN AND MELANIN PRODUCTION incoming radiation (Zareba et al., 2006). Many forms
of eumelanin with slightly different structures and
The remarkable range of brown hues seen in human colors exist, and the sheer heterogeneity of natural
skin is produced by melanin. “Melanin” is the collective eumelanin contributes to its wide array of physical
term for a large family of molecules that are found and chemical properties.
in many types of organisms, including fungi, inverte- Eumelanin owes many of its physiological proper-
brates, and vertebrates. Melanins are classified as ties to the way in which it is packaged in cells.
192
Skin Coloration 193
Melanins are produced in specialized cells called Tadokoro et al., 2005). Those with naturally light skin
melanocytes, which are found at the lowest level of have smaller and more sparsely distributed melano-
the epidermis at the junction with the dermis. Melano- somes, which contain varying amounts and kinds of
cytes are considered one of the types of “immigrant eumelanin and smaller amounts of its lighter-colored
cells” in the skin because their precursor cells migrate cousin, pheomelanin (Ancans et al., 2001; Thong et al.,
into the skin from the neural crest during early embry- 2003; Lamason et al., 2005). Like eumelanin, pheome-
onic development. These cells establish connections lanin is variable in its structure and its different forms
with neighboring keratinocytes in a carefully orches- vary in color from yellow to red (Ito, 2003). In humans,
trated process of signaling and adhesion (Haass et al., pheomelanin is most obvious in the hair of people from
2005). Melanocytes produce melanin in the skin while northernmost Europe (including the British Isles),
the developing embryo is still very young, but the pro- but is present in small quantities in the skin of most
cess ramps up slowly. Babies are born pale and their people (Thody et al., 1991; Alaluf et al., 2002; Ito, 2003;
melanocytes do not produce melanin at full capacity Meredith and Sarna, 2006). Subtle variations in skin
until puberty (Robins, 1991). color between people that we easily detect with the
Melanin is produced within melanocytes in small eye – the reddish, yellowish, bluish, and other hues
membrane-bound packages units called melanosomes. that are often remarked on in artistic descriptions of
As melanosomes mature and become full of melanin human skin – are due to different proportions of the
they move into the dendrites of the melanocyte, and different forms of eumelanin and pheomelanin in the
are from there transferred into adjacent keratinocytes. skin (Thody et al., 1991; Alaluf et al., 2002; Hennessy
This process is precisely controlled by genetic and et al., 2005; Kongshoj et al., 2006).
hormonal factors, but it can be accelerated in most The complexity of the pigment production system
people by exposure to UVR (Fitzpatrick et al., 1961; is such that loss of pigmentation can occur in many
Prota, 1992a, 1992b; Aroca et al., 1993; Kollias, different ways. Different types of albinism in humans
1995b; Nordlund, 1995; Kollias et al., 1996; Li et al., are due to genetic mutations affecting different parts
2001; Thong et al., 2003; Brenner and Hearing, 2008). of the pigment production pathway or melanocytes in
One melanocyte supplies melanin to about 36 kerati- different parts of the body (Robins, 1991; Sulaimon
nocytes in a precisely and intricately choreographed and Kitchell, 2003; Hornyak, 2006; Sturm, 2006; Duffy
process that is controlled by keratinocytes (Jimbow et al., 2007). Melanocytes can be entirely absent or
et al., 1976; Schallreuter, 2007). Loss of contact fail to produce melanin, or melanosomes can fail
between melanocytes and keratinocytes allows the to mature and be transferred into keratinocytes
former to break free of their positions in the epidermis, (Bahadoran et al., 2003). The affliction vitiligo occurs
start dividing rapidly, and leave the normal confines of when the ability to produce pigment in the skin is
the skin. This marks the beginning of the most serious lost only in patches on the body. The absence of
type of skin cancer, melanoma (Haass and Herlyn, normal skin color on part or all of the body can have
2005; Haass et al., 2005). Within keratinocytes, mel- serious consequences for health and self-image, and
anin tends to be distributed in supranuclear caps that so considerable research has been devoted to these
protect the cell nuclei from incoming UVR photons afflictions. Individuals with albinism and vitiligo are
(Kobayashi et al., 1998; Gibbs et al., 2000). Cells with at greater risk for skin cancer because of the absence
supranuclear melanin caps contained significantly less of protective melanin in some or all of the skin
DNA photoproducts (cyclobutane pyrimidine dimers (Johnson, 1998). Levels of serum folate and vitamin
and 6–4 photoproducts) than those without. B12 are lower in vitiligo patients (Montes et al., 1992;
People of different skin colors differ in the amounts Kim et al., 1999).
and types of melanin they produce, and in the ways in The distribution of pigment over the surface of the
which the melanins are packaged and distributed in body is not always even, as in the case of freckles
the skin. The mechanisms controlling melanin produc- (ephelides or solar lentigines), which are small, flat
tion are genetically determined and involve the regula- spots of melanin that occur mostly in people with very
tion of a series of chemical pathways in which enzyme lightly pigmented skin. They vary in color from yellow
tyrosinase plays a major part (Sturm et al., 2001; Alaluf (predominantly pheomelanin-containing) to very dark
et al., 2002; Sulaimon and Kitchell, 2003; Brenner and brown (predominantly eumelanin-containing) and
Hearing, 2008). The color and physical properties of develop in a random pattern on the skin in response
skin are also caused by differences in the size and to repeated sun exposure. Ephelides are freckles which
distribution of melanosomes in the skin, and in the most commonly appear on the faces of children after
types of melanin they contain. People with naturally sun exposure (Rhodes et al., 1991). The other type of
darkly pigmented skin have melanosomes that are freckle, solar lentigines (“liver spots”), populates the
large, clumped, and filled with eumelanin (Szabo hands and faces of older people. These freckles tend
et al., 1969; Alaluf et al., 2002; Thong et al., 2003; to be darker than childhood freckles, and occur in
194 Nina G. Jablonski
people with wide range of skin colors as the result of low UVR exposures cause measurable damage to DNA
sun damage. in all people regardless of color, so there is no such
A person’s genetically determined or baseline pig- thing as completely UVR-proof skin (Brenner and
mentation is referred to as their constitutive pigmenta- Hearing, 2008).
tion, in contrast to their facultative pigmentation, People with light constitutive pigmentation (Types
which is developed as the result of exposure to UVR. I and II) make very little melanin in their melanocytes,
Over the last two centuries, the description of skin and have no or negligible ability to produce melanin
colors has developed from verbal portrayals of skin when exposed to UVR (Fitzpatrick and Ortonne, 2003).
colors (“white,” “yellow,” “black,” “brown,” and “red”) When exposed to UVB (290–320 nm), in particular,
to color-matching methods such the von Luschan people with Types I or II skin react by mounting a
scale (von Luschan, 1897; Olivier, 1960) to reflectance strong inflammatory reaction resulting in sunburn.
spectrophotometry (Lasker, 1954a; Wassermann, Erythema and pain are obvious and uncomfortable
1974) as reviewed elsewhere (Jablonski, 2004; Parra, symptoms of sunburn, but the hidden damage done to
2007). Reflectance spectrophotometry is the preferred the connective tissues and DNA of the skin is more
method for the objective study of skin pigmentation serious because of the connection with premature aging
because the incident light used and the distance and skin cancer, including melanoma (Cleaver and
between the light source and the subject are invariable Crowley, 2002; Matsumura and Ananthawamy, 2004).
(Wassermann, 1974). Constitutive skin pigmentation is People with moderately or darkly pigmented skin
measured on parts of the body not routinely exposed to (Types III–VI) produce melanin in their skin when they
sun, with the inner (medial) surface of the upper arm are exposed to UVR. The tanning reaction is complex
being preferred. Comparability of measurements and fully develops over the course of days and weeks, if
made by color-matching techniques and reflectance exposure to the sun persists. In many people, the initial
spectrometry, and between skin reflectance measure- response of the skin to strong sunlight is the rapid
ments made by different types of reflectance spectro- development of blotchy grey-brown looking skin
photometers has been a problem in anthropology known as immediate pigment darkening (IPD). This
(Jablonski, 2004; Parra, 2007) that has still not been mechanism appears to involve the redistribution and
completely solved. Many human populations that were photo-oxidation of existing melanin in keratinocytes of
studied using color-matching methods or older types of the epidermis (Ortonne, 1990; Young, 2006). Normal
reflectance spectrophotometers cannot be restudied tanning is also known as delayed tanning to distinguish
because they are extinct or have become thoroughly it from IPD. Delayed tanning involves the stimulation
admixed with neighboring populations. of melanocytes into a program of long-term activity.
Melanin is produced in the skin of most people The visible darkening that occurs within a week of sun
following exposure to UVR through the tanning exposure is as a result of upward movement of melanin
response. Nearly everyone can develop a “tan” when in the epidermis, not because of the making of new
exposed to strong, UVR-containing sunlight, but some pigment (Tadokoro et al., 2005; Nielsen et al., 2006b).
people can produce more melanin than others (Lasker, Increases in melanin production occur later, and
1954b; Lee and Lasker, 1959; Agar and Young, involve slower responses of melanocytes to modifica-
2005; Tadokoro et al., 2005). Dermatologists classify tions in the regulation of tyrosinase activity (Ortonne,
human skin by “phototype” or “sun reactive type” from 1990; Alaluf et al., 2002). Chronic exposure to UVR can
Phototype (or Type) I (always burns, does not tan) to result in a near doubling of melanin content in the skin
Type VI (never burns, always tans darkly) (Fitzpatrick relative to baseline amounts. The degree to which tans
et al., 1961; Fitzpatrick, 1988; Rubegni et al., 1999; are protective against the harmful effects of UVR has
Fitzpatrick and Ortonne, 2003). All people have similar been the subject of considerable debate. Heavy tans
numbers of melanocytes, but people with Types V or VI afford little protection against UVR-induced damage
have about four times as much melanin in their skin as to DNA relative to the amount provided by naturally
those with Type I skin, and will produce much more dark skin (Tadokoro et al., 2005; Nielsen et al., 2006a).
melanin and so develop deeper facultative pigmenta- For moderately pigmented skin, however, tanning
tion when exposed to UVR (Tadokoro et al., 2005). affords some protection against seasonally varying
Higher melanin content affords more protection intensities of UVR because melanin production
against damage to DNA and other biologically import- increases slowly in relation to gradually rising UVR
ant molecules (Ortonne, 2002; Meredith and Sarna, levels in the spring and so prevents bad sunburns from
2006). The four-fold difference in melanin content in being experienced during the height of summer levels
naturally dark people translates into a seven- to eight- of UVB. This almost certainly accounts for the evolu-
fold difference in protection against damage to DNA tion of tanning abilities. Naturally dark skin affords
(Tadokoro et al., 2005), but even the darkest skin does great protection against UVR because of its higher
not protect completely against damage to DNA. Very eumelanin content, the superior UVR-absorbing
Skin Coloration 195
abilities of large clumped melanosomes, and because including UVR (Walsberg, 1988). Compensation for the
the eumelanin can be mobilized faster from deep in the loss of this protection came from evolution of increased
epidermis and brought to a position closer to the thickness of the epidermis, especially of the most super-
surface of the skin more quickly (Nielsen et al., 2006a). ficial layer, the stratum corneum (Montagna, 1971;
Constitutive skin pigmentation gradually fades Madison, 2003) and from evolution of permanent pro-
after early adulthood as part of the process called tective pigmentation in the skin to prevent the most
chronological aging. In people older than around 30 energetic and damaging wavelengths of radiation from
years, the number of active melanin-producing cells penetrating into the body.
decreases on average by about 10–20% per decade Among modern humans, skin pigmentation as meas-
(Quevedo, 1969; Ortonne, 1990; Fisher et al., 2002) ured by reflectance spectrometry is highly correlated
in a pattern that is strongly correlated with the human with latitude (Roberts and Kahlon, 1976, Tasa et al.,
reproductive career. 1985), but is even more highly correlated (r2 ¼ 0.93)
with the annual average erythemal dose of UVR (the
UVMED, or ultraviolet minimal erythemal dose, is the
THE EVOLUTION OF HUMAN SKIN minimum dose of UVR, mostly UVB, necessary to pro-
PIGMENTATION duce a noticeable reddening of lightly pigmented skin)
(Roberts, 1977; Jablonski and Chaplin, 2000; Chaplin,
The evolution of skin pigmentation in humans is inex- 2001, 2004). The strength of the correlation between
tricably connected to the evolution of hairlessness and UVMED and skin reflectance at all wavelengths is greater
enhanced sweating abilities (Jablonski, 2006). The than with any other single environmental factor
probable ancestral condition of skin in the human (Chaplin, 2001, 2004). The strength of this correlation
lineage was pale skin covered by dark hair (Jablonski strongly suggests the action of natural selection acting
and Chaplin, 2000), and loss of functional body hair northward and southward to produce two reciprocal
was associated with the evolution of an efficient whole- clines of skin pigmentation (Relethford, 1997).
body cooling system based on sweating (Wheeler, Significant insight into the evolution of human skin
1985; Amaral, 1996; Jablonski and Chaplin, 2000; pigmentation has come from studies of the MC1R
Jablonski, 2006). Modern humans have eccrine sweat (melanocortin 1 receptor) locus, one of several genes
glands distributed all over their bodies, and those on that contributes to skin, hair, and eye pigmentation in
the forehead, back, and chest are especially quick to humans. In modern Africans, this gene exhibits no
respond to heat and exertion (Sato and Dobson, 1970, variation, but outside of Africa it is highly variable.
Cotter et al., 1995, Shibasaki et al., 2006). Evaporation The absence of variation in African forms of the gene
of sweat slightly reduces the temperature of the surface provides evidence of strong positive selection or select-
of the body, thereby cooling the blood flowing in the ive sweep occurring around 1.2 million years ago
capillaries of the skin, including the scalp (Adams et al., (Rogers et al., 2004) and the maintenance of a func-
1975, 1992, Cabanac and Brinnel, 1985). The slightly tional constraint on variation (purifying selection) in
cooled venous blood returning to the heart is oxygen- Africa thereafter (Rana et al., 1999; Rees, 2000; Makova
ated and then recirculated to the periphery, including and Norton, 2005). The ancestral form of MC1R, along
the temperature-sensitive brain (Cabanac and Masson- with probable contributions from other pigmentation
net, 1977; Brinnel et al., 1987; Falk, 1990; Jablonski, genes (Shriver et al., 2003; Norton et al., 2007), makes
1993). Sweating is most effective in cooling the body possible the production of large amounts of eumelanin
when there is less hair on the surface to slow evapor- in the melanocytes of the skin and appears to have
ation, hence the connection between an increased been so effective in improving health and reproductive
number of eccrine sweat glands and functionally naked success that people carrying it quickly outnumbered
skin. Naked skin is more vulnerable to environmental and replaced those who did not. This evidence indi-
influences, and the naked skin of humans differs from cates that permanent, heavily melanized skin evolved
that of close but hairier primate relatives in its greater pari passu with functionally hairless skin richly
water resistance and resistance to abrasion (Montagna, endowed with eccrine sweat glands, and was the ances-
1981). The genetic basis of these differences is just tral condition for the genus Homo (Jablonski and
beginning to be understood (Chimpanzee Sequencing Chaplin, 2000; Jablonski, 2006).
and Analysis Consortium, 2005), but genes related to
the epidermal proteins that contribute to the barrier
Natural selection and the evolution
functions of the skin, the integrity of sweat glands, and
of dark skin pigmentation
the delicate nature of our body hair (Langbein et al.,
2005) appear to be of particular importance. Lacking What selective factors led to dark pigmentation being
protective fur or hair also renders naked body skin established by a selective sweep and being maintained
much more vulnerable to damage from solar radiation, by purifying selection in regions of high UVR? The
main hypotheses that have been advanced to account incidence of melanoma in the last 50 years are the
for this have been lowered mortality due to skin cancer, result of lightly pigmented people being exposed to
enhanced fitness because of protection against the more intense or longer periods of sunlight and UVR
harmful effects of sunburn, the benefits of dark pig- (Jemal et al., 2001) and experiencing more painful
mentation with respect to predation avoidance or sunburns (Kennedy et al., 2003; Veierod et al., 2003)
while hunting in poorly lit forested environments, because of migration to sunny places or involvement in
enhanced fitness because of the antimicrobial proper- recreational sun-tanning (Leiter and Garbe, 2008), and
ties of eumelanin, and enhanced fitness due to the cannot be considered typical of our species prior to the
protection of folate against its breakdown by UVR. twentieth century.
These hypotheses will be discussed in turn. The protection conferred by eumelanin-rich skin
Darkly pigmented, eumelanin-rich skin protects against sunburn is raised (but rarely elaborated in
against considerable damage to DNA caused by UVR writing) as a possible factor responsible for the selec-
(Miyamura et al., 2007), and is associated with much tion of dark pigmentation in regions of high UVR. The
lower rates of skin cancer than lightly pigmented skin prevalence and effects of serious sunburns have been
(Barker et al., 1995; Armstrong and Kricker, 2001; studied mostly in relation to skin cancer, and strong
Diepgen and Mahler, 2002; Soininen et al., 2002; links between repeated painful sunburns before the age
Tadokoro et al., 2003; Saraiya et al., 2004; Agar and of 20 years and cutaneous melanoma have been estab-
Young, 2005; Pfeifer et al., 2005; Rouzaud et al., 2005; lished (Kennedy et al., 2003). Serious sunburns alone
Brenner and Hearing, 2008). The protective effects of are rarely linked to harmful immediate side-effects,
eumelanin on DNA structure were established by an however, despite the pain and discomfort they cause.
experimental study showing that heavily pigmented There are no data to support the claim that sunburns
melanocytes resumed proliferation faster after UVB cause damage sufficient to affect reproductive success.
irradiation than can lightly pigmented ones, and that Only one study was found in the literature that
DNA from lightly pigmented melanocytes contained examined the incidence of serious sunburns. This was
significantly higher numbers of cyclobutane pyrimi- a 1-year prospective study from an Irish hospital in
dine dimers than did DNA from heavily pigmented which it was reported 4.7% of all burns (16 cases)
melanocytes after irradiation with increasing doses of treated in the hospital were caused by serious sunburn
UVB (Barker et al., 1995; Cleaver, 2000; Cleaver and (Cronin et al., 1996). Two cases only required inpatient
Crowley, 2002). In contrast, the production and pres- intravenous fluid replacement, and no deaths were
ence of pheomelanin in lightly pigmented skin appears reported. The absence of other reports in the medical
to increase the risk of oxidation stress in melanocytes. literature on serious immediate consequences of sun-
This, combined with the limited ability of pheomelanin burn suggests that the sunburn is not in itself a serious
to absorb UVR, may lead to an elevated skin cancer risk cause of morbidity and mortality and would have had
among light-skinned individuals (van Nieuwpoort only minor evolutionary potency. The malign effects of
et al., 2004). The damaging effects of UVR on DNA serious sunburns on the activity of eccrine sweat
structure, especially those relating to the generation glands and thermoregulation have also been mooted
of carcinogenic cyclobutane pyrimidine dimers, are in connection with the evolution of dark-skin pigmen-
now widely recognized (Barker et al., 1995; Pflaum tation. To date, only one study has carefully evaluated
et al., 1998; Epel et al., 1999; Kielbassa and Epe, the effect of sunburn on sweat rates and thermoregula-
2000; Cleaver and Crowley, 2002; Sinha and Hader, tion in humans (Pandolf et al., 1992). In this study,
2002; Pfeifer et al., 2005; Schreier et al., 2007). These lightly pigmented subjects receiving artificially
are, however, mostly associated with the initiation of induced sunburns were able to maintain thermal
squamous and basal cell carcinomas (Dwyer et al., homeostasis during vigorous exercise despite reduc-
2002; Christenson et al., 2005), which are skin cancers tion of sweat rates 24 hours after UVB exposure
that mostly affect people toward the end or after their (Pandolf et al., 1992). These results suggest that sun-
reproductive careers (Blum, 1961; Jablonski and burn-induced damage to sweat glands does not
Chaplin, 2000; Rigel, 2008). Of all the major types of adversely affect thermoregulation to the extent that
skin cancer, cutaneous malignant melanoma is the was envisioned by some, and that damage to sweat
only type with a high incidence rate among people of glands was not a major selective force in the evolution
reproductive age, but overall incidence and mortality of dark pigmentation in regions of high UVR.
rates for melanoma prior to the mid-twentieth century Theories brought forth to account for the evolution
were very low (<5 per 100 000) (Diepgen and Mahler, of dark pigmentation based on the benefits of eumela-
2002). The low rates of mortality due to melanoma nin other than those related to protection against solar
prior to 1970 (Jemal et al., 2001) argue that it was radiation have not gained empirical support. The pro-
unlikely that melanoma was a significant driver of posal that dark skin evolved because it provided super-
selection for darkly pigmented skin. Increases in the ior concealment against visual detection in dark forest
Skin Coloration 197
environments (Cowles, 1959) was not unreasonable Folate is a water-soluble B vitamin that occurs
when it was thought that much of human evolution naturally in food. Folate deficiency was long ago
took place in forests and not more open, well-lit envir- recognized as the primary cause of megaloblastic
onments. But this proposition is now untenable in light anemia but, by the late 1980s, folate’s importance was
of the more than 40 years of paleoanthropological enhanced by discovery of its role in role in nucleic acid
research demonstrating that most of the evolution of synthesis (Green and Miller, 1999). Since then, studies
the human lineage took place in well- or brightly lit of the interdiction of cell proliferation as consequence
woodland or woodland–grassland environments. of folate deficiency have had wide ramifications for
Another group of hypotheses have suggested that dark understanding of normal development and birth
pigmentation evolved primarily because eumelanin- defects, and normal cell division and neoplasia. Folate
rich melanosomes and melanocytes confer strength to also participates in the formation of myelin and is
immune systems that are challenged by tropical infec- important in the production of many neurotransmit-
tious diseases and parasites (Wassermann, 1965, 1974; ters including serotonin (Djukic, 2007). Because the
Mackintosh, 2001). Although eumelanin-rich melano- compound cannot be made by the body, humans get
somes exhibit antimicrobial properties and may bol- folate only from food or from supplements of folic acid,
ster the innate immune system, these benefits are of the synthetic form of folate. The best sources of natural
secondary importance compared to those they confer food folates are green leafy vegetables (the word folate
in direct connection with UVR protection. The ubiquity comes from the Latin “folium” for leaf), fruits, and
of eumelanin in nature appears to be due primarily it dried beans and peas. Healthy levels of folate are diffi-
its role as a physical absorber of UVR and chemical cult to maintain in the body because natural food
neutralizer of the noxious by-products produced by folates are unstable, suffer from low bioavailability,
UVR bombardment or, in other words, as a built-in and tend to break down when foods are boiled or
sunscreen (Epel et al., 1999) not as an antimicrobial stored (Gregory, 1995; McNulty and Scott, 2008). Nat-
agent. The antimicrobial hypothesis also does not ural folates are converted into various forms that are
explain the evolution of deep-tanning abilities in used immediately or stored in the liver. Folate deficien-
human populations living remote from the tropics cies can be caused by insufficient intake of folate,
and tropical diseases (e.g., Inuit and native Tibetans), improper absorption of the vitamin from the gut, or
but exposed to high levels of environmental UVR. when serum folate is broken down by alcohol or
If reduced fitness or mortality due to UVR-induced UVR (Anonymous, 1983; Tamura and Halsted, 1983;
skin cancers, sunburns, a weakened immune system, Mastropaolo and Wilson, 1993; Komaromy-Hiller
or an absence of appropriate camouflage were not the et al., 1997; Suh et al., 2001; Off et al., 2005; Steindal
main selective pressures driving the evolution of dark et al., 2006; Der-Petrossian et al., 2007). They are also
skin pigmentation in high UVR environments, then influenced by genetic factors, notably by variations
other agents capable of exerting these effects must be in the methylenetetrahydrofolate reductase locus
identified. (MTHFR) that affect DNA methylation and synthesis
The effects of UVR on biological systems are and homocysteine metabolism (Blom et al., 2006).
wide-ranging, multifarious, and mostly destructive The essential connections between folate metabol-
(Caldwell et al., 1998; Madronich et al., 1998; Roths- ism and the evolution of skin pigmentation are, firstly,
child, 1999). The deleterious effects of UVR on DNA the relationship between UVR exposure and folate
have been emphasized because of the direct relation- breakdown and, secondly, the relationship between
ship between mutations of DNA in the skin and skin UVR-induced folate deficiency and reduced fitness
cancer. Ultraviolet radiation also breaks down other due to failures of normal embryogenesis and sperm-
molecules of great biological importance, including atogenesis (Jablonski, 1992; Jablonski and Chaplin,
the B vitamin, folate. The possibility that UVR might 2000). Numerous epidemiological studies and metas-
be implicated in the breakdown of folate in human tudies from the late 1980s onward have indicted folate
blood was first mooted 30 years ago when it was recog- deficiencies during pregnancy in the etiology of neural
nized that folate levels in a small number of human tube defects (NTDs) (Bower and Stanley, 1989, 1992;
patients were lowered significantly 1 hour after sub- Minns, 1996; Copp et al., 1998; Fleming and Copp,
jects were exposed to simulated strong sunlight 1998; Molloy et al., 1999; Lucock, 2000; Williams
(Branda and Eaton, 1978). The authors of the paper et al., 2005). These and other studies demonstrating
proposed that the light-induced breakdown of folate the many important roles of folate were influential
might be related to the evolution of skin color, but in the introduction in 1998 in the fortification with
did not pursue research along this avenue probably folic acid of the enriched flour used to make most
because the importance of folate in normal develop- breads and breakfast cereals in the United States and
ment and cell proliferation was not then fully Canada. In the last 20 years, the relationship between
appreciated. folate deficiencies and NTDs has been thoroughly
documented, and the importance of folate status is epidemiological studies, in which the prevalence
stressed for all women of reproductive age (Bailey, of NTDs relative to skin color has been examined
1995; de Bree et al., 1997; Neuhouser et al., 1998; (Buccimazza et al., 1994; Williams et al., 2005; Besser
Caudill et al., 2001; Scott, 2007). Plentiful supplies of et al., 2007). Although these studies did not establish a
folate are essential to maintain the high rates of cell definitive cause-and-effect relationship between skin
proliferation in the embryo, particularly in the develop- color and NTDs, they indicated trends warranting
ing central nervous system where high levels of folate- further investigation. Darkly pigmented skin appears
carrier protein are expressed (Djukic, 2007). Neural to contribute to the maintenance of healthy folate
tube defects occur when the normal processes of cell status by actively protecting circulating folate from
division in the early nervous system are disrupted. In UVR photolysis, resulting in fewer NTDs being
the fourth week of human intrauterine development, observed in more darkly pigmented groups. Many
the neural tube closes like a two-ended zipper from the factors probably account for the fact that the most
middle simultaneously toward the head and tail ends. darkly pigmented women suffer the lowest rates of
At this time the embryo and its nervous system are NTDs, but the data suggest that high melanin concen-
particularly sensitive to low folate levels because rates trations in the skin have a protective effect and this
of cell proliferation are high. Failure of the two edges warrants more explicit epidemiological investigation.
of the tube to fuse securely can cause holes at the head The existence of a causal relationship between photo-
end – leading to the fatal defect of anencephaly – or degradation of folate and increased incidence of NTDs
more distally, leading to the various forms and attend- in humans is also strengthened by the observation of a
ant disabilities of spina bifida. Folate is also important conception peak of May–June among NTD births in the
for normal sperm production, and folate status is Northern Hemisphere (Marzullo and Fraser, 2005).
increasingly being investigated as a reason for male
infertility (Mathur et al., 1977; Ebisch et al., 2006).
The evolution of light skin pigmentation
The emerging view is that folate status is crucial to
reproductive success primarily because of its dual The evidence that permanent dark skin pigmentation
importance in embryonic differentiation and sperm evolved as protection against the deleterious effects of
production, but that it is unstable and subject to many UVR is overwhelming, and research is mounting that
environmental and genetic factors. eumelanin confers photoprotection against both folate
Evidence-based in vivo experiments for a causal photolysis and indirect and direct damage to DNA.
relationship between UVR exposure and folate degrad- This accounts for the concentration of darkly pig-
ation in the human body has been slow to accumulate mented indigenous peoples in areas of high UVR,
because the problem does not lend itself easily to mostly within the tropics (Jablonski and Chaplin,
experimental testing on human subjects. As a result, 2000; Jablonski, 2004), but it does not explain the clinal
much of the research has involved exposure of human distribution of increasingly lightly pigmented skin out-
blood plasma outside of the body to UVR and the use of side of the tropics. As was the case with dark skin
model systems in which folic acid was subjected to pigmentation, numerous hypotheses have been put
different wavelengths of UVR (Off et al., 2005; Nielsen forward to account for the evolution of light skin pig-
et al., 2006b; Vorobey et al., 2006; Der-Petrossian et al., mentation. The three major hypotheses that have been
2007). This research has shown that folate breaks put forward and that are discussed below in turn are:
down in the presence of UVR, and that the longer, resistance against cold injury; loss of pigmentation
more deeply penetrating UVA rays are particularly through the probable mutation effect; and enhanced
damaging. Ultraviolet A causes folate to degrade in potential for production of vitamin D in the skin under
three phases into a series of chemical intermediates, conditions of reduced sunlight intensity.
and some of these in turn act to sensitize folate to According to the cold-injury hypothesis, darkly pig-
further degradation and also damage DNA. Photode- mented skin was actively selected against in colder and
gradation of the main form of folate in human plasma, generally higher latitude environments because it was
5-methyltetrahydrofolate (5-MTHF), involve reactive more susceptible to frostbite (Post et al., 1975). People
oxygen species generated by UVA and blue visible light afflicted with frostbite would be less able-bodied, less
and accelerated in the presence of riboflavin (Steindal able to forage and hunt successfully, and more suscep-
et al., 2006). High concentrations of melanin signifi- tible to possibly fatal secondary infections such as gan-
cantly reduced folate destruction in vitro through grene (Post et al., 1975). This hypothesis was based on
absorption and scattering of UVA (Nielsen et al., observations of a slightly higher incidence of frostbite
2006b). These studies support the theory that the in twentieth-century US combat troops of African
major factor contributing to the evolution of dark skin descent than those of European descent. The reasons
pigmentation was breakdown of folate caused by for the slight difference in frostbite incidence revealed
UVR. This theory is also supported by the results of by the study are still not well understood, and there is
Skin Coloration 199
good reason to suspect that variables relating to The strength of UVR, and of UVB in particular,
the equipment issued to soldiers were not adequately declines greatly north of the Tropic of Cancer
taken into account (Kittles, 1995). The difference and south of the Tropic of Capricorn (Johnson et al.,
in response to extreme cold probably has less to do 1976, Relethford, 1997; Chaplin, 2001, 2004; Hitch-
with pigmentation than with other aspects of skin cock, 2001; World Health Organization, 2002; Lucas
structure such as the distribution of fat and connective et al., 2006). Humans living outside of the tropics face
tissue (Steegmann, 1967, Kittles, 1995), or differences high UVR levels in the summer months, but extremely
in the temperature responsiveness of peripheral low levels, especially of UVB, in the fall and winter.
capillaries. In light of the many deleterious effects of UVR on
The theory that lightly pigmented human skin biological systems, low levels of UVR might be
evolved in the absence of selective pressure was first regarded as universally beneficial, but they are not.
advanced within the framework of the probable muta- The single overwhelmingly positive action of UVR is
tion effect (Brace, 1963). The resulting “structural photosynthesis of vitamin D3 (cholecalciferol) in the
reduction” was seen as the main factor initiating the skin of land-living vertebrates (Coburn et al., 1974;
evolution of lightly pigmented skin outside of the trop- Henry and Norman, 1984; Webb and Holick, 1988;
ical regions under the highest selective pressure for Holick, 1997, 2003). Without the biologically active
dark pigmentation (Brace, 1963). The subsequent form of vitamin D, normal life and reproduction are
spread of light pigmentation was then said to be pro- not possible. The global disease burden linked to the
moted by assortative mating (Kittles, 1995), with vitamin D deficiencies caused by low UVR exposure
sexual selection leading to even lighter pigmentation now exceeds that connected with high UVR exposure
in females (Frost, 1988; Aoki, 2002). Doubt has been (Lucas et al., 2008a).
cast on the structural reduction hypothesis mainly Vitamin D3 is made in the skin when UVR pene-
because relaxation of selection on dark pigmentation trates the skin and is absorbed by 7-dehydrocholesterol
would be expected to produce a more random pattern (7-DHC) in the epidermis and dermis to form previta-
of skin pigmentation outside of high UVR regions, min D3. This reaction only occurs at the Earth’s surface
rather than the structured pattern characteristic in the presence of wavelengths of 290–315 nm in the
of the action of purifying selection that is observed UVB range, with peak conversion occurring at 295–297
(Norton et al., 2007). The clinal distribution of skin nm. Photosynthesis of vitamin D3 in the skin depends
pigmentation that is seen in the Eastern Hemisphere upon season and latitude, time of day, and on the
and, with lesser intensity, in the Western Hemisphere amount pigment and thickness of the skin (Mawer
is one of the most significant characteristics of human and Davies, 2001; Lips, 2006). This reaction also
skin and strongly suggests the operation of natural becomes less efficient with advancing adult age
selection. A large proportion of global landmass is con- because of an age-dependent decrease in 7-DHC in
centrated in regions that receive low UVR on an annual the skin (Maclaughlin and Holick, 1985; Cerimele
basis, and the distribution of skin pigmentation in et al., 1990; Holick, 1995). Inherent limits on circulat-
modern humans is arranged such that increasingly ing levels of previtamin D3 exist because continued
lighter-skinned populations are distributed are in areas sunlight exposure causes the photoisomerization of
of incrementally lower UVR (Relethford, 1997; Chaplin previtamin D3 to lumisterol and tachysterol (Holick
and Jablonski, 1998). et al., 1981) regardless of skin color. In order to become
Mechanisms to account for the clinal distribution biologically active, vitamin D3 must undergo a two
of light skin pigmentation in regions of increasingly successive hydroxylation steps, first in the liver to 25
low UVR must explain how this distribution was (OH)D3 (calcidiol) (also known as 25-hydroxyvitamin
achieved during the process of hominid dispersal and D (25(OH)D)) and then in the kidney under the influ-
maintained in the face of migration (gene flow) ence of parathyroid hormone (PTH) into the active
(Barton, 1999). The stable clinal arrangement of metabolite, 1,25(OH)2D3 (calcitriol) (also known as
human skin pigmentation among indigenous peoples 1,25-dihydroxyvitamin D3 (1,25(OH)2D)). Extrarenal
indicates the action of stabilizing selection over a production of calcitriol occurs in several other tissues
spatially varying optimum condition. If dark pigmen- in humans, including breast, placenta, colon, and pro-
tation was the original condition for the genus Homo state, where it is used locally and does not enter the
and has been maintained as an adaptation to high systemic circulation (Norman, 2008). (The naming
levels of UVR, then what must be elucidated is the conventions for vitamin D used here are those of the
selective pressure responsible for establishing and Joint Commission of Biochemical Nomenclature of the
maintaining light pigmentation in regions of low International Union of Pure and Applied Chemistry
UVR. Put another way, the question to be addressed and International Union of Biochemistry [IUPAC-IUB
surrounds the selective advantage of a continuously Joint Commission on Biochemical Nomenclature,
varying cline of UVR-attenuating pigment in the skin. 1982].) It is calcitriol that acts as a steroid hormone
through binding to its specific intranuclear receptor, status is also linked to impaired immune system activ-
the vitamin D-receptor (VDR), and subsequently ity, specifically Th1-mediated (T-helper-cell-type-1-
modulates the transcription of responsive genes such mediated) autoimmunity and infectious immunity
as that of calcium binding protein, which regulates (Cantorna and Mahon, 2005; Cantorna et al., 2008).
mineral ion homeostasis (Lips, 2006; Norman, 2008; Hypovitamosis D is correlated with a weakened
St-Arnaud, 2008). Vitamin D is also available in low immune response to influenza virus, and appears to
quantities in some foods, specifically vitamin D3 in oily be predispose children to respiratory infections in gen-
fish and liver, and vitamin D2 in some plants including eral (Cannell et al., 2008). Developmental vitamin
many fungi (Bjorn and Wang, 2000; Chen et al., 2007; D deficiency in animal models has been linked to
van der Meer et al., 2008). Egg yolks contain vitamin D3 impairment of numerous activities of the brain
only if the egg-producing chickens have been given (McGrath et al., 2004; Harms et al., 2008). Thus, the
vitamin-D-rich feed, and cow’s milk contains it only if connection between adequate vitamin D status and
it has been specifically fortified at the time of process- fitness is not limited to development and maintenance
ing (Lamberg-Allardt, 2006). Dietary sources of vita- of the strength of the musculoskeletal system, but to
min D must be converted into the biologically active normal development and functioning of the immune
form via the same hydroxylation steps undergone by system and brain.
cutaneously produced vitamin D3. The most common The fact that UVA cannot initiate vitamin D photo-
clinical assays used to assess vitamin D status measure synthesis is significant for understanding the evolution
levels of calcidiol or 25(OH)D in the serum, hence the of human skin pigmentation. Most of the Earth is
commonly used shorthand “serum 25(OH)D.” Expos- bathed in UVA and visible light for most of the year
ure to UVB does not automatically result in elevation of because their longer wavelengths can pass easily
serum 25(OH)D or of serum 1,25(OH)2D levels through the atmosphere. Shorter UVB wavelengths
because the hydroxylation steps occurring in the liver are more easily destroyed by atmospheric ozone or
and kidney are under multiple hormonal influences. reflected by other molecules and dust in their path.
The most obvious function of vitamin D in humans The Earth’s surface receives relatively little UVB (and
is in the building and maintenance of the bony none of the even more energetic and uniformly harm-
skeleton. The essential connection between vitamin D ful UVC) because oxygen and ozone in the atmosphere
status and bone health was established because serious are excellent filters of these kinds or radiation
vitamin D deficiency was linked to the highly visible (Caldwell et al., 1998; Hitchcock, 2001; World Health
and disfiguring bone disease, nutritional rickets. The Organization, 2002; Kimlin, 2004). The amount of UVB
classical view of vitamin D action has been that it reaching the Earth’s surface depends on the solar
exerts its effects on bone only indirectly, as a hormone, zenith angle. Ultraviolet B falls on the equator and
through regulation of absorption of calcium and phos- within the tropics throughout the year because its path
phorus from the gut. This view is now being supple- from the Sun through the atmosphere is short. Outside
mented by the recognition that vitamin D directly of the tropics the angular path taken by the sun’s rays
modifies the activity of osteoblasts and chondrocytes, require that UVR pass through a thicker layer of
and many other nonclassical target tissues (Henry and atmosphere to reach the Earth’s surface, resulting in
Norman, 1984; Norman, 2008; St-Arnaud, 2008; Wolff the destruction or reflection of most UVB en route.
et al., 2008). The discovery of VDRs in tissues of the Locations farther away from the equator receive less
brain, heart, stomach, pancreas, skin, gonads, in the UVB on an annual basis and demonstrate less potential
activated T and B lymphocytes of the immune system, for cutaneous vitamin D biosynthesis (Jablonski and
and in 28 other tissues has led to a growing appreci- Chaplin, 2000; Chaplin, 2004; Chen et al., 2007). The
ation of the varied and important roles vitamin D plays major exception to this is the Tibetan Plateau, which
in the body (Henry and Norman, 1984; Norman, 2008). receives higher UVB than other locations at its latitude
The active form, 1,25(OH)2D3 (calcitriol), influences (~34 N) because of the thinness of the atmosphere
cell biology relevant to cancer through VDR-mediated at its high altitude (average elevation 4500 m).
gene transcription and inhibition of abnormal cell div- Once produced in the skin, vitamin D3 can be
ision (hyperproliferation) in several organs. For this broken down by UVA wavelengths (315–335 nm), even
reason, chronic deficiencies in vitamin D may be asso- after exposures as short as 10 minutes in nontropical
ciated with breast, prostate, colon, ovarian, and pos- sunshine (Webb and Holick, 1988; Webb et al., 1989).
sibly other cancers (Garland et al., 2006; Fleet, 2008; The vitamin D3 content of samples of lightly pigmented
Grant, 2008). Strong correlations between hypovitami- skin declined by 80% when exposed to 3 hours of sun-
nosis D and a range of cardiovascular diseases also light in June in Boston (42.2 N) (Webb et al., 1989),
suggest a causal relationship between vitamin and photolysis of vitamin D3 was observed at lower
D status and the health of cardiac and smooth muscle rates during the nonsummer months. This mechanism
(Chen et al., 2008, Kim et al., 2008). Low vitamin D is significant for two reasons. Firstly, it works – along
Skin Coloration 201
with previtamin D3 photoisomerization – to prevent primarily by the skeletal deformities of nutritional

vitamin D toxicity, which was considered in the past a rickets, including those affecting the pelvic shape and
causal explanation for the evolution of dark skin childbirth in females (Neer, 1975; Holick et al., 1981;
pigmentation (Loomis, 1967). Secondly, it means that Clemens et al., 1982; Clements et al., 1987; Webb and
UVA breaks down vitamin D3 even during parts of the Holick, 1988; Littleton, 1991’ Matsuoka et al., 1991;
year when no UVB is present in the sunlight to catalyze Fogelman et al., 1995; Goor and Rubinstein, 1995;
previtamin D3 photosynthesis (Webb and Holick, 1988). Brunvand et al., 1996; Mitra and Bell, 1997; Jablonski
The hypothesis that light skin pigmentation evolved and Chaplin, 2000; Kreiter et al., 2000; Malvy et al.,
outside of the tropics as an adaptation to lower levels of 2000; Holick, 2003; Shaw, 2003; Vieth, 2003; Calvo
sunlight and diminished ability to produce vitamin et al., 2005; Bouillon et al., 2006; Lips, 2006; Chen
D in the skin has been put forward with successive et al., 2007; Parra, 2007; Tran et al., 2008). The hypoth-
refinements for many years (Murray, 1934; Loomis, esis that the light skin pigmentation is due to positive
1967; Jablonski and Chaplin, 2000). Today, it is the selection for depigmentation, that is, pigmentation
hypothesis that is supported by the largest and most lighter than the ancestral highly pigmented condition
convincing body of experimental and observational for the genus Homo, has been strengthened in the
evidence. The many functions described above for last decade by two further lines of evidence. The
vitamin D denote that hypovitamosis D – comprising first connects hypovitamosis vitamin D to the possible
vitamin D deficiency and the less clearly defined increased prevalence of certain cancers and comprom-
vitamin D insufficiency – is a serious public health ised immune status, as described above. The evidence
problem (Vieth, 1999, 2003; Hathcock et al., 2007; for these phenomena is strong, as judged by prodigious
Kimball et al., 2008). Nutritional rickets in infants daily increases in the number of published studies
and children is the most obvious manifestation of the available through major internet search engines. The
condition because the attendant problems of bone second line of evidence comes from molecular genetic
calcification in the developing skeleton lead to studies and points to lightly pigmented phenotypes in
visible skeletal deformities such as bowing of the humans having been selected for multiple times
weight-bearing long bones. Deformities of the female (Lamason et al., 2005; Lalueza-Fox et al., 2007; Norton
pelvis associated with severe nutritional rickets impair et al., 2007) and having been maintained by purifying
and sometimes preclude normal childbirth, leading to selection (Makova and Norton, 2005; Norton and
mortality of the infant, the mother, or both (Vieth, Hammer, 2007; Norton et al., 2007). In order to under-
2003). In children and juveniles, the disease can also stand why positive selection for depigmentation
involve the less visible symptoms of dental agenesis occurred, it is useful to look in greater detail at the
and muscle weakness (sarcopenia or myopathy). New properties of eumelanin in human skin.
evidence suggests that depressed bone mineral accrual Eumelanin is such a good natural sunscreen that it
due to rickets in fetal development may affect prepu- competes with 7-DHC for UVB photons in darkly pig-
bertal bone mass accumulation (Kimball et al., 2008). mented skin (Types V and VI) to greatly slow produc-
In adults, hypovitaminosis D is sinister because it usu- tion of previtamin D3 (Clemens et al., 1982; Holick,
ally betrays few or no obvious physical manifestations 1987; Matsuoka et al., 1991; Goor and Rubinstein,
or acute symptoms. In the musculoskeletal system, the 1995; Mitra and Bell, 1997; Jablonski and Chaplin,
osteomalacia and sarcopenia associated with hypovi- 2000; Kreiter et al., 2000; Malvy et al., 2000; Skull
taminosis D are silent problems that can lead to et al., 2003; Vieth, 2003; Webb, 2006; Chen et al.,
increased morbidity from accidental falls (Wolff et al., 2007; Cosman et al., 2007; Hathcock et al., 2007; Tran
2008). In other systems, vitamin D deficiency and et al., 2008). When eumelanin is distributed through-
insufficiency – especially beginning in infancy or out the entire thickness of the epidermis, within the
childhood – are associated with increased, but still melanosomes of keratinocytes and as “melanin dust”
not rigorously quantified, risk of certain cancers and (disintegrated melanosomes), it absorbs most of the
autoimmune and infectious diseases, as described incident UVB. Penetration of UVR is related to the
above. Prospective long-term studies involving the amount and the distribution of eumelanin, with large,
tracking of vitamin D status and the incidence of a more superficial, eumelanin-filled melanosomes being
wide range of infectious and chronic diseases across a more effective in reducing previtamin D3 production
wide range of human populations are needed. (Nielsen et al., 2006b). People with lightly pigmented
Until the last decade, arguments for the evolution (Type II) skin can produce previtamin D3 in their skin
of light skin pigmentation outside of high UVR regions at a rate 5–10 times faster than those with darkly pig-
rested primarily on comparative physiological and mented (Type V) skin (Clemens et al., 1982; Matsuoka
epidemiological data from modern human populations et al., 1991; Jablonski and Chaplin, 2000; Webb, 2006;
that showed a convincing cause-and-effect relationship Armas et al., 2007; Chen et al., 2007). This poses strict
between hypovitaminosis D and reduced fitness caused geographic limits on the distribution of darkly
60⬚N 60⬚N
30⬚N
30⬚N
30⬚S
30⬚S
60⬚S 60⬚S
12.1. The geographic distribution of the potential for cutaneous vitamin D production, modified from
a previous publication (Jablonski and Chaplin, 2000). For lightly pigmented skin, pre-vitamin D3 can
be produced within the tropics during most of the year. Outside of the tropics, the absence of UVB in
sunshine in some (or most) months prevents the vitamin D photosynthesis. Lightly pigmented people
living within the zone denoted by horizontal lines experience at least one month during the year when
they cannot produce vitamin D in their skin due to shortage of UVB. Lightly pigmented people living in
the cross-hatched zone experience short bouts of UVB at the height of the summer only and cannot
produce enough vitamin D from solar sources to satisfy their annual physiological requirements, and
thus must supplement their diet with vitamin-D-rich or vitamin-D-fortified foods. For darkly pigmented
people, the potential for cutaneous vitamin D production is considerably less under all UVR regimes
due to the natural sun-screening effect of eumelanin. See text and a previous publication (Jablonski
and Chaplin, 2000) for further discussion.
pigmented people outside of high UVB areas unless that there was no selective pressure for loss of skin
vitamin-D-rich foods or vitamin D supplements are pigmentation in nontropical hominids because of the
consumed (Figure 12.1) (Jablonski and Chaplin, 2000; efficiency of cutaneous vitamin D production even in
Jablonski, 2004; Chen et al., 2007). darkly pigmented skin and because of the body’s
The potential for cutaneous photosynthesis of capacity for long-term vitamin D storage (Robins,
previtamin D3 is minimal in the winter at latitudes 1991) is not supported by any evidence. Depigmented
greater than 37 , and on an annual basis people living skin was necessary for continuous human habitation
north of 50 cannot produce enough previtamin D3 to at high latitudes. At the highest latitudes, rich dietary
satisfy their physiological needs (Jablonski and sources of vitamin D such as fatty fish, marine
Chaplin, 2000; Chen et al., 2007; Holick et al., 2007). mammals, reindeer or caribou offal, and vitamin D-
The problem is compounded by the facts that main containing lichens were also essential for maintenance
bioactive form of vitamin D3, 1,25(OH)2D (calcitriol), of health in the near-absence of UVB. These resources
has a half-life of approximately 15 hours in the circula- were and are heavily exploited by the indigenous
tion and can itself be broken down by UVA penetrating inhabitants of the Arctic such as the Inuit and Saami.
the skin, as described above (Holick et al., 1981; Webb Copious genetic information relevant to the question
and Holick, 1988; Webb et al., 1989; Jones, 2008). The of the evolution of skin depigmentation in human evolu-
half-life of serum 25(OH)D (calcidiol) is about two tion has been discovered in the last decade and has been
weeks. Storage of vitamin D as 25(OH)D (calcidiol) in summarized authoritatively elsewhere (Rees, 2003;
human fat and skeletal muscle is possible (Mawer Sturm, 2006; Lao et al., 2007). It is now recognized that
et al., 1971, 1972) and, in the absence of UVB or dietary as many as eight different genes contribute to variation
vitamin D, the stores have a half-life of about two in human skin human pigmentation, including the
months (Jones, 2008). These stores are insufficient to MC1R locus (Sturm, 2006; Lao et al., 2007; Myles et al.,
provide adequate supplies of the vitamin in the absence 2007). Statistically significant correlations between
of cutaneous production or dietary sources of the vita- the frequencies of four of these loci and specific
min, especially in lean people. The persistent claim skin pigmentation phenotypes have been recognized
Skin Coloration 203
(Lao et al., 2007). These studies are significant because Variant forms of the MC1R gene are associated
they make possible the testing of hypotheses about the with red hair and pale skin in northern Europeans,
role of selection in determining variation in human but different variants of MC1R do not themselves cause
pigmentation. As more genetic information on skin skin color differences within this group (Sturm et al.,
pigmentation is uncovered, it is salutary to remember 2001, 2003). Rather, these differences appear to be due
that the pigmentation phenotypes, not genes, were the to action and interaction of other loci including
objects of natural selection. In the evolution of skin SLC24A5, SLC45A2 (MATP), and TYR (Sturm et al.,
pigmentation, as in the evolution of any complex trait, 2001; Lamason et al., 2005; Sturm, 2006; Norton
different combinations of genes affecting different parts et al., 2007). The particular importance of the SLC24A5
of pigment production pathways worked at particular locus in determining skin pigmentation in northern
times under particular environmental circumstances to Europeans was demonstrated in an elegant series of
produce reproductively successful phenotypes. experiments involving golden and wild-type zebrafish
Variation in the MC1R locus of modern African (Lamason et al., 2005). Golden zebrafish possess the
peoples is minor and consists mostly of synonymous slc24a5 or golden gene, and exhibit fainter stripes and
substitutions (John et al., 2003); the functional signifi- smaller and less dense pigment granules than those of
cance of the few nonsynonymous substitutions found the wild-type zebrafish. These differences parallel
has not been investigated. The apparent absence of those that distinguish the melanosomes of lightly and
functionally significant variation in this locus in darkly pigmented human skin. Using ingenious meth-
modern native African peoples demonstrates the odology and elegant experimental design, the research
action of stabilizing or purifying selection that has team established that the human orthologue of the
worked to mostly eliminate variations in pigmentation variant SLC24A5 gene that caused the golden zebrafish
that would not be able to survive and reproduce under phenotype was probably responsible for the melanoso-
high UVR regimes. In contrast, considerable variation mal structure and the light, pheomelanin-dominated
at the MC1R locus is observed outside Africa, especially pigmentation of northern European people (Lamason
in northern Europe (Rana et al., 1999; Rees, 2003). et al., 2005). This study showed that the European
High levels of polymorphism at the MC1R locus, and variant of SLC24A5 was an important contributor to
specific sets of polymorphisms at that locus, are asso- variability in human skin color, and that a single DNA
ciated with red hair and lightly pigmented skin, which base change (a single nucleotide polymorphism or SNP)
has limited ability to produce melanin and which is that had undergone a selective sweep affected ancient
highly susceptible to skin cancers (Rees, 2000, 2003, European human populations (Norton and Hammer,
2004, 2008). The contributions of other loci including 2007). The evolution and spread of the SLC24A5 variant
SLC25A5 (Lamason et al., 2005; Norton et al., 2007) accounts for 25–38% of the difference in skin color
and SLC45A2 (MATP) (Graf et al., 2007) to skin between modern populations of Europeans and
pigmentation are now actively being investigated. Africans (Lamason et al., 2005). The absence of the
Humans living at high latitudes in Paleolithic and European variant of SLC24A5 in Africans and in lightly
Neolithic times with depigmented skin were probably pigmented East Asians implies that independent selec-
at no significantly higher risk of developing lethal skin tion for depigmentation occurred in the populations
cancer because they were relatively short-lived and leading to modern East Asians (Lamason et al., 2005;
did not have the ability to migrate long distances into Myles et al., 2007; Norton and Hammer, 2007; Norton
significantly higher UVR regions where they would be et al., 2007). When combined with the evidence of the
more prone to DNA-damaging sun exposure. Neanderthal MC1R polymorphism, this finding indi-
Variant forms of the MC1R gene associated with cates that depigmented skin evolved independently
lightly pigmented skin also appear to have evolved three times in evolution through the action of positive
independently in the Neanderthal lineage (Lalueza- selection on hominid populations living in areas receiv-
Fox et al., 2007). The protein-coding sequence for the ing low UVB. The discovery of an early Homo fossil from
MC1R allele retrieved from the bone of a Neanderthal Turkey with a pathological lesion probably caused by
from Germany was a loss-of-function variant compar- tuberculosis provides further evidence that mainten-
able in effect but different in sequence from any of ance of vitamin D status sufficient to protect against
those found in modern humans (Lalueza-Fox et al., chronic infectious diseases has been a challenge since
2007). This finding suggests that Neanderthals evolved the first African dispersal event (Kappelman et al., 2008).
a functional variant of the MC1R gene independently Skin pigmentation among the indigenous peoples
from modern humans as they dispersed into northerly of the New World follows a similar clinal pattern to
latitudes, and thus supports the inference for the con- that seen in the Old World, but is less pronounced
vergent evolution of depigmented skin in the Neander- (Jablonski and Chaplin, 2000). This may be due to
thal lineage published prior to the elucidation of the the shorter length of time of habitation (15 000 years
gene sequence (Jablonski and Chaplin, 2000). or less), the enhanced ability of the dispersing
populations to buffer themselves culturally from the the action of parathyroid hormone-related protein
exigencies of new environments using clothing and (Kovacs, 2008). In the face of moderate maternal vita-
shelter, or a combination of both factors. Most indigen- min D deficiency, PTH concentrations rise in an appar-
ous New World peoples have excellent tanning abilities ent reflection of the need to maintain adequate plasma
(Lasker, 1954b; Lee and Lasker, 1959). calcium concentrations through PTH-induced osteoly-
sis (Okonofua et al., 1987). In cases of severe pre-
existing maternal vitamin D deficiency, however, preg-
Sexual dimorphism in skin pigmentation
nancy precipitates osteomalacia in women and nutri-
Adult human females are consistently lighter in pig- tional rickets in neonates (Kreiter et al., 2000; Nozza
mentation than males from the same population and Rodda, 2001; Kovacs, 2008). Few prospective stud-
(Frost, 1988, 2007; Jablonski and Chaplin, 2000; Mad- ies have examined the vitamin D status and the course
rigal and Kelly, 2007). This fact has invited consider- of calcium of women or neonates over the course of
able speculation as to why this discrepancy evolved. pregnancy and lactation (Hollis and Wagner, 2004a,
Explanations based on the central role of sexual selec- 2004b; Kimball et al., 2008) and none have examined
tion have dominated the literature and popular these parameters over the course of a relatively long
press and a reported global preference for lighter- lactation period such as that humans experienced in
than-average skin color in sexual partners offered as prehistory. We do not know the length of lactation in
proof of male preference for lighter female mates Paleolithic humans, but it probably was at least two
(Frost, 1988, 2005, 2007; Aoki, 2002). The evolution of years, based on averages for modern gathering and
lighter pigmentation in females of lightly pigmented hunting people (Lee, 1980; Lunn, 1994). Despite the
populations in low UVR regions, in particular, has controversies and limitations of currently available
been seen as evidence of the strength of sexual selec- data, the evidence now available suggests that chronic-
tion acting outside of the constraints of melanization ally depressed vitamin D levels in actively reproducing
maintained by purifying selection within the high-UVR women would compromise the female skeleton over
tropics (Aoki, 2002). A recent study in which the degree successive pregnancies and lengthy periods of lacta-
of sexual dimorphism in skin pigmentation was exam- tion, and would be associated with progressive hyper-
ined relative to latitude revealed no evidence support- parathyroidism. It would also, in the most serious
ing this claim (Madrigal and Kelly, 2007). cases, compromise the integrity of the neonatal skel-
A different perspective on sexual dimorphism in eton, and the future calcium status of children and
skin pigmentation comes from the recognition that juveniles so compromised as infants. Hypovitaminosis
human females require significantly higher amounts D in pregnant and lactating women and their neonates
of calcium during pregnancy and lactation and, thus, would also lead to depressed functioning of the
must have lighter skin than males in the same environ- immune system, with potentially deleterious or lethal
ment in order to maximize their cutaneous vitamin D3 consequences. Thus, strong clinical evidence continues
production (Jablonski and Chaplin, 2000). The extra to support the hypothesis that lighter skin pigmenta-
calcium needed for fetal and neonatal skeletal growth tion in females evolved primarily as means to enhance
is insured by increased maternal calcium absorption, the potential for cutaneous vitamin D production and
which is in turn facilitated by higher circulating levels maintain healthy long-term calcium status and skeletal
of vitamin D3 (Lucas et al., 2008b). The literature on health. Culturally based sexual selection probably
the vitamin D status of pregnant and lactating women acted to increase levels of sexual dimorphism in skin
and their neonates has grown dramatically in recent pigmentation in many populations (Jablonski and Cha-
years (Kreiter et al., 2000; Hollis and Wagner, 2004a, plin, 2000; Jablonski, 2004, 2006). This effect has con-
2004b;, Hollis, 2005; Kovacs, 2008; Lucas et al., 2008b). tinued and may be increasing, as assortative mating is
Controversies exist over the relationship between vita- increasingly influenced by the widespread propagation
min D status and calcium metabolism in adult women of images of lightly pigmented females (Jones, 2000; Hill,
during pregnancy, lactation, and the months immedi- 2002; Jablonski, 2006; Rondilla and Spickard, 2007).
ately following the cessation of lactation, and over
the relationship between maternal and fetal/neonatal
vitamin D status and calcium metabolism. Dark SKIN PIGMENTATION AND HEALTH IN
pigmentation and prolonged breast-feeding without MODERN HUMAN POPULATIONS
supplementation are clear risk factors for vitamin
D deficiencies in women and their neonates (Kreiter One of the most biologically significant cultural differ-
et al., 2000; Nozza and Rodda, 2001). To some extent, ences between prehistoric and current populations of
the healthy calcium status of neonates is insured Homo sapiens is the potential for long-distance, high-
against low maternal vitamin D status because calcium speed migration. The ability of humans to migrate long
can be liberated from maternal bony stores through distances through the use of domesticated animals,
Skin Coloration 205
wheeled vehicles, watercraft, motorized transport, and by purifying selection, and concomitant excellent tan-
air transportation has made it possible for people to ning abilities. In populations dispersing to regions of
move between regions with markedly different UVR lower UVR, incrementally lighter pigmentation evolved
regimes within single human lifetimes. This has initially by positive selection for depigmentation and
resulted in many people living under UVR conditions has been maintained by stabilizing selection. One of
very different in kind and intensity from those in which the great remaining challenges in the study of human
their ancestors evolved. The concomitant disease skin color evolution is estimation of the intensity of
burden has been unexpected and high, and is visited selection pressure experienced by humans as they dis-
both upon lightly pigmented people living under high persed into different UVR regimes, and estimation of
UVR regimes and darkly pigmented people living the time course for the evolutionary changes in pigmen-
under low UVR conditions. These problems are further tation. This is an active area of research in which the
exacerbated by cultural practices, from sun-bathing author is now involved.
among the light-skinned to veil-wearing among the Our understanding of human skin color genetics is
dark-skinned. Modern humans are excellent at making still incomplete, but comparative genomics is now pro-
cultural adjustments to changed physical circum- viding evidence that skin color is a polygenic trait con-
stances, but often the adjustments are insufficient to trolled by several genes that interact in complex ways.
compensate for what has been lost and most are made Skin, hair, and eye color are all affected by multiple
in the absence of evolutionary knowledge. For genes, and their pleiotropic interactions. In some
example, the cultural encouragement of sun avoidance populations some variant forms of the genes account
and sun protection as a means to reduce the incidence for more of the variation in skin color rather than in
of skin cancer risk has been successful, but was hair color and vice versa. Combinations of different
launched in the absence of adequate cultural mechan- forms of the genes have brought about the complex
isms for insuring adequate vitamin D levels in the and continuous variation in skin coloration that we
absence of UVR exposure. Modern humans ignore see in modern humans. With respect to evolutionary
their evolution history at their peril. biology, what is important is that the human pigmen-
tation phenotype has evolved to maintain an optimum
balance of penetration of UVR over a spatially varying
CONCLUSIONS landscape of solar radiation. The genetic evidence
demonstrating that light skin pigmentation was
Our understanding of the evolution of human skin selected for three times independently in hominids in
pigmentation has benefited greatly from new kinds of response to the selective pressure of low UVR regimes
data and analytical methodologies being brought to highlights the importance of skin pigmentation in
bear on one of the oldest problems of anthropology maintaining physiological homeostasis and healthy
and human biology. It is now possible for data on skin reproductive status. It also denotes the lability of skin
reflectances in modern indigenous human populations pigmentation in evolution and the unsuitability of
to be examined in conjunction with genetic and geno- skin reflectance as a character in cladistic analyses
mic studies of the nature and interaction of pigmenta- or in phenotypic sorting of human populations into
tion genes. Experimental simulations of the reactivity color-based groups that are assumed to have genetic
of real or simulated human skin to the components of similarity or propinquity.
solar radiation are common. Direct measures of UVR
and other physical characteristics of the environment
are enabling powerful, geographically explicit explor- DISCUSSION POINTS
ations of the relationships between characteristics of
the physical environment and the human organism. As 1. What functions does eumelanin play in human
a result of these new data and new kinds of analyses, skin?
we are gaining a much clearer understanding of the 2. What hypotheses have been put forward to account
factors that have influenced the evolution of skin pig- for the evolution of darkly pigmented skin in
mentation during the history of the human lineage. humans inhabiting equatorial latitudes? What cri-
The human pigmentation phenotype has been deter- teria need to be taken into account when assessing
mined by natural selection to maintain an optimum the validity of the statement, “skin pigmentation is
balance between photoprotection and photosynthesis adaptive”?
over spatially varying conditions of ultraviolet irradi- 3. How is vitamin D made in the skin? What factors
ation. In regions of high UVR, including the regions of affect the body’s ability to produce vitamin D?
tropical Africa where the genus Homo and modern 4. What evidence supports the hypothesis that the
Homo sapiens emerged, this was achieved through the evolution of lightly pigmented skin was promoted
evolution of dark constitutive pigmentation maintained by positive selection?
5. What are some of the main health effects experi- Armstrong, B. K. and Kricker, A. (2001). The epidemiology
enced by humans when they live under solar of solar radiation and skin cancer. In Sun Protection in
regimes different from those of their ancestors? Man, P. U. Giacomoni (ed.). Amsterdam: Elsevier Science,
6. How does culture mitigate or intensify the effects of pp. 131–153.
skin pigmentation on human physiology? Aroca, P., Urabe, K., Kobayashi, T., et al. (1993). Melanin
biosynthesis patterns following hormonal stimulation.
Journal of Biological Chemistry, 268, 25650–25655.
ACKNOWLEDGEMENTS Bahadoran, P., Ortonne, J.-P., King, R. A., et al. (2003).
Albinism. In Fitzpatrick’s Dermatology in General Medicine,
I thank Michael Muehlenbein for inviting me to I. M. Freedberg, A. Z. Eisen, K. Wolff, et al. (eds), 6th edn.
contribute to this volume, and for his patience. I am New York: McGraw-Hill, pp. 826–835.
grateful to George Chaplin for numerous detailed dis- Bailey, L. B. (1995). Folate requirements and dietary recom-
mendations. In Folate in Health and Disease, L. B. Bailey
cussions about the evolution of human skin color, for
(ed.). New York: Marcel Dekker, Inc., pp. 123–151.
his constructive review of the first draft of this manu-
Barker, D., Dixon, K., Medrano, E. E., et al. (1995).
script, and for preparing Figure 12.1. I also thank Tess
Comparison of the responses of human melanocytes with
Wilson for assisting in the gathering of reference mater- different melanin contents to ultraviolet B irradiation.
ial and for maintaining my bibliographic database. Cancer Research, 55, 4041–4046.
The constructive comments of two reviewers greatly Barton, N. H. (1999). Clines in polygenic traits. Genetics
improved the final draft of the manuscript. The Research, 74, 223–236.
financial support provided by an Alphonse Fletcher Sr. Besser, L. M., Williams, L. J. and Cragan, J. D. (2007). Inter-
Fellowship is also gratefully acknowledged. preting changes in the epidemiology of anencephaly and
spina bifida following folic acid fortification of the US
grain supply in the setting of long-term trends, Atlanta,
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13 Classic Markers of Human Variation
Robert J. Meier
INTRODUCTION repeats (VNTRs), single nucleotide polymorphisms

(SNPs), and microsatellite polymorphisms. In short,
The door to the study of genetically based variation in these are DNA markers. Hence, the time frame for
humans cracked open at the beginning of the twentieth reviewing markers will encompass anthropological
century with the discovery by Landsteiner (1901) of field and laboratory studies carried out beginning at
ABO blood group substances whose Mendelian mode turn of the twentieth century roughly through
of inheritance was later established by Bernstein the1980s. This end point is just prior to the widespread
(1924). Needless to say, an early trickling of discoveries use of polymerase chain reaction (PCR) and the
has led to a flood over the past century of new and developing application of DNA markers to population
important revelations concerning the nature and sig- studies. As a timetable guide, Roychoudhury and Nei
nificance of human genetic variation. This chapter will (1988) were referred to for selecting markers from
cover approximately three-fourths of that history as it those that had been identified by the date of that pub-
unfolded via the discovery and elucidation of a host of lication. The major categories of human markers will
markers. A helpful review of genetic markers known as include: blood group polymorphisms, serum protein
of the early 1970s and their role in the study of human and enzyme variants, and an open-ended set of
evolution can be found in Crawford (1973). Another markers that are of microevolutionary and anthropo-
recent review of classic markers and their contribution logical interest. Polymorphism is used here to signify
toward understanding North American Native genetic two or more alleles at a given locus each exceeding 1%
variation appeared in O’Rourke (2006). Two current frequency.
textbooks that provide substantial coverage of trad- Tables follow that list these traditional markers.
itional markers, along with DNA markers and other It should be noted that marker identification
topics relevant to human biological variation, are pertains to an earlier time period and may not conform
Mielke, et al. (2006) and Molnar (2006). to presently known markers and their allele or haplo-
Over the years markers have come to mean fairly type (a combination of alleles at multiple linked
consistently defined hereditary units. An early refer- loci) labels. However, chromosome locations for the
ence to the use of the term is found in Race and Sanger markers are current and were extracted from the
(1962) who discuss markers, in their case human blood National Center for Biotechnology Information (NCBI)
groups, as characters that help to locate genes on website.
chromosomes. This was, of course, early in any Some sampling of the total number of classical
attempts to construct physical gene maps. Sometime markers was done so as to not overwhelm the chapter.
later, genetic markers were associated with specific The selection process was based on how much infor-
polymorphic loci that defined particular segments of mation was available for the marker, how widely it was
chromosomes (Cavalli-Sforza et al., 1994). In essence, studied across human populations, and how informa-
genetic markers today signify genes or other identifi- tive the marker was in bringing out important
able segments of DNA whose inheritance can be con- points pertaining to human variation. Several classic
sistently documented and mapped. works are available for anyone interested in a more
For purposes of this chapter, classical markers will complete and in depth compilation of markers. These
refer to those historically researched phenotypically include; Race and Sanger (1962), Buettner-Janusch
observable variants that for the most part preceded (1966), Giblett (1969), Mourant et al., (1976), Harris
DNA methodologies that presently deal with nucleotide (1980), Mourant (1983). Tills et al., (1983), Livingstone
sequences in various representations, such as mito- (1985), Roychoudhury and Nei (1988), and Cavalli-
chondrial DNA (mtDNA), variable number tandem Sforza et al. (1994).
214
Classic Markers of Human Variation 215
The organization for describing classical markers TABLE 13.1. Blood cell and secretion markers.
centers on five main topics: basics of marker identifi-
cation and their expressed phenotypic physiological Locus Chromosome Markers Discovered
function, historical application of markers in classify- ABO 9q34.1–q34.2 A1,A2,B,O 1900/30
ing human populations and races, application of Secretor 19p13.1– Se,se 1932
markers to population studies and microevolutionary p13.11
processes, markers and their relationships with dis- Lewis 19p13.3 Lea,Leb,le 1946/54
eases, and contemporary use and future prospects for Rh 1p36.11 *D,C,c,E,e 1940
classic markers. MN/Ss 4q28–q31 MS,Ms,NS, 1927/47
Ns
P 22q11.2– P,p 1927
IDENTIFYING RED BLOOD CELL MARKERS q13.2
Luth./Auber. 19q13.2 Lua,Lub 1945/61
An early method for detecting variants of hereditary Kell/Sutter 7q33 K,k 1946/58
expression, beyond that of parental selection and Duffy 1q21–q22 Fya,Fyb,Fy0 1950
crossing as devised by Mendel, were serological reac- Kidd 18q11–q12 Jka,Jkb 1951
tions. Discovery of blood group markers arose through Diego 17q21–q22 Dia,Dib 1955
unintended consequences of transfusions, involving Xg Xp22.23 Xga,Xg 1962
donor–recipient mismatches that led to adverse clin- Hemoglobin 11p15.5 (b) A,S,C,E 1947/49
ical outcomes for patients. Working off these unfortu- HLA 6p21.3 *
A,B,C,DQ, 1962/64/67
nate medical mishaps, Landsteiner’s discovery in 1900 DR
of the ABO system was based on laboratory tests of a
Note: *These closely linked marker loci have multiple alleles
person’s blood cells against serum from a different and haplotypes.
person. Particular combinations of cells and sera pro-
duced visible agglutination reactions between red
blood cell surface antigens and corresponding bivalent is the O phenotype, did in fact possess an antigen
antibodies found in the serum. Following extensive called H. This finding provided an alternative name
cross matches of this sort, Landsteiner was able to for the system, ABH. The H antigen is in fact present
identify persons who had either A or B antigens, in virtually all ABO phenotypes, in decreasing amount
both A and B, or neither. The success of his work partly from O type to AB. One exception to this is the Bombay
depended on the fact that the ABO system has natur- phenotype O that lacks red blood cell H antigen, and
ally occurring antibodies that form shortly after birth. carries a corresponding anti-H, as well as anti-A
This then, was the launch into a succession of subse- and anti-B in the serum.
quent discoveries of both improved medical proced-
ures requiring blood transfusion, and in identifying
additional blood group marker systems. SOLUBLE ANTIGENS
Table 13.1 provides a listing of antigens, their
chromosome location and their marker notations, In addition to blood cell surfaces, antigenic markers
and year of discovery. Some of these markers, for also can appear in water soluble form through out
example in the Rh system, were originally observed in body fluids, with particular reference here to saliva.
a manner similar to that noted above, that is, due to Presence of salivary antigens in the ABH system were
adverse transfusion reactions. Others were found detected with the inhibition test, where known antisera
through deliberate laboratory procedures of injecting were mixed with the tested saliva, and then checked
human blood cells into animals (often rabbits) and against known red cell antigens to see which antisera
extracting any produced antiserum or agglutinin, had already reacted with or had been inhibited, and
which then could be tested against humans for positive thus revealed the identity of the antigen.
or negative reactions. An example of this is anti-N in ABH secretion (now designated as FUT1) of soluble
the MN system. Interestingly, plant extracts (lectins) antigens turned out to be just the first system that
also were found to differentially react with receptor was later found to be among a linkage group on
sites of human blood cell antigens. Also in the MN chromosome 19 that also included the Secretor locus
system, anti-N reagent was extracted from Vicea gra- (or FUT2) itself along with Lewis (or FUT3), Lutheran,
minea, a legume. In the case of the ABO system, anti-A1 and Auberger antigenic markers. Of historical signifi-
was made from Dolichos biflorus, and while Ulex euro- cance, autosomal linkage of Secretor and Lutheran
paeus (also a legume in the gorse bush family) differ- was the first of its kind to be shown (Mohr, 1951).
entiated A2 from A1 and also was used to establish Another linkage to note here is that between Kell and
that persons who lacked both A and B antigens, that Sutter blood groups on chromosome 7. There has also
216 Robert J. Meier
been evidence that Kell is linked with the PTC trait, b-chain locus on chromosome 11. This locus is of par-
a marker to be discussed later. Linkage detail on ticular interest here due to its maintaining elevated
Kell/Sutter and the secretor loci noted above was marker frequencies in human groups that are at
incomplete or not known at the time of major marker increased risk for contracting endemic malaria, a topic
compilations, such as Roychoudhury and Nei (1988). that will be covered later on.
Linkage between MN and Ss was known, and allele
combinations of these two systems, which undergo
little recombination, should probably be treated as HLA SYSTEMS
haplotypes. At the molecular level of the red blood cell
membrane, it is now established that the M and N Mode of inheritance: Multiple autosomal loci and multiple codo-
antigens are bound to glycophorin A (GPA) while the minant linkage groups or haplotypes.
S and s antigens are carried by glycophorin B (GPB).
Finally, Table 13.1 contains the HLA systems. Human
The final red blood antigen system to mention here is
leukocyte antigen (HLA) haplotypes are found on white
Xg, obviously so-named because it is located on the
blood cells and expressed at several closely linked loci
X chromosome. It was discovered through conven-
on chromosome 6. In a broader context, HLA pertains
tional serological methods in 1962. That year marks
to the major histocompatibility complex (MHC) as
the end of the initial period of discovery of red blood
found throughout vertebrates. The MHC is of funda-
cell polymorphisms, at least those that figured most
mental importance in defining an individual’s
prominently in anthropological field studies.
immunological identity and consequently establishing
Modes of inheritance for red blood cell and secretor groups can a defense system against potential pathogens. The five
be codominant (as in the MN group), dominant-recessive (as in HLA loci as listed in Table 13.1 contained markers for
the Rhesus group for the D antigen), a combination (as in the tracing human population relationships and for inves-
ABO group), or sex-linked (as in the Xg group). For some groups, tigating associations with diseases. Three of these
detection of heterozygote phenotypes depends upon the specifi-
(HLA-A, -B, and -C) are tested through serological reac-
city of the serological reagents. Molecular methods now make
tions, while the remaining two (HLA-DQ and -DR) are
many of the earlier dominant-recessive designations obsolete or
investigated through cytotoxic methods. Specific HLA
incomplete.
haplotypes will be discussed later in the context of
For a reasonably up-to-date compilation of red blood disease associations.
cell markers, dealing with those covered here and
many more as well, the reader is referred to The Blood
Group Antigen FactsBook (Reid and Lomas-Francis, SERUM PROTEINS
1997), wherein you will find descriptions and displays
of the molecular basis of the markers along with add- The plasma or fluid portion of blood contains a large
itional categories of information befitting a complete number of kinds of proteins, most of which were found
reference source. to be polymorphic as well as variable among different
human populations. Table 13.2 lists serum protein
markers that will be reviewed here. The workhorse
HEMOGLOBINS method for separating and identifying serum proteins
was electrophoresis that utilized a variety of prepar-
Mode of inheritance: Two autosomal loci, segregating multiple ations, buffers, and media.
codominant alleles, but depending upon which of the pleiotropic
phenotypic expressions are considered, there can also be domin-
ant and recessive conditions. ALBUMINS
Table 13.1 also lists hemoglobins, which make up
about 85% of the protein structure of red blood cells. Mode of inheritance: Autosomal codominants with AlA allele
Considering their early and continuing significance in controlling the common albumin, and several variants,
such as Al Naskapi, found in varying frequency in different
microevolutionary studies, they could command a sep-
populations.
arate table. Electrophoresis was used in identifying
hemoglobin variants. A primary function of hemo- Albumins make up about one-half of all serum
globin is to bind oxygen molecules while blood has proteins. Their genetic control is found on chromo-
infused the lungs and transport this oxygen throughout some 4. One of their main functions is to bind and
the circulatory system where it is then released during carry other serum constituents, such as fatty acids
metabolic activity. A very large number of hemoglobin and steroids, and they also control fluid volume
variants have been found (Livingstone, 1985) but this outside the cell. Albumin studies were regularly
review will focus on major variants found at the carried out by field researchers around the world and
TABLE 13.2. Serum protein, enzyme, and other

with major exceptions, notably the Saami of Norway
markers. and Sweden (Roychoudhury and Nei, 1988).
Protein Chromosome Marker

Albumin 4q11–q13 AlA,Al Naskapi and
others
IMMUNOGLOBULINS (GM AND INV)
1 2
Gc 4q12–q13 Gc ,Gc
Mode of inheritance: Multiple autosomal dominant/recessive
Gm (IgG) 14.q32.33 Haplotypes
1 2
and codominant alleles and linkage groups.
Inv (IgK) 2p12 Inv ,Inv
Haptoglobin 16q22.1 Hp1,Hp2 Immunoglobulins serve as the body’s defense system
Transferrin 3q22.1 TfC,TfB,TfD by forming antibodies against foreign intruders
Enzyme Chromosome Marker such as bacteria and viruses. By the 1960s two types
Carbonic 8q13–q22.1 CA II (B),CA II (C) of globulins were identified, namely, Gm (IgG of the
anhydrase heavy chain of the antibody molecule) and Inv
G6PD Xq28 G6PD deficient (IgK/Km of the light chain). Gm is located on chromo-
HEXA (Tay–Sachs) 15q23–q24 HEXA deficient some 14, while Inv is mapped to chromosome 2.
Lactase 2q21 Lactase persistent, Marker variants and haplotypes segregating at these
deficient two loci were observed to differ by human population
PAH (PKU) 12q24.1 PAH deficient and region, probably as the immune responses were
Red cell acid 2p25 Pa,Pb,Pc adaptively tailored to specific pathogenic threats.
phosphatase So while there are coding genes underlying Gm and
Trait/condition Chromosome Marker label Inv, their expression is mediated by environmental
Cerumen 16q12.1 Wet type, dry type circumstances. Schanfield (1980) conducted a study
(ear wax) of the anthropological usefulness of genetic markers
Cystic fibrosis 7q31.2 Affected in differentiating regional and continental populations
(CF)
and concluded that Gm haplotypes, along with HLA
PTC tasting 7q34 Taster, nontaster
haplotypes and the Duffy blood group, were the leaders
in carrying out this task when compared against a
bank of red blood cell, serum protein and enzyme
markers. Two essential components of usefulness were
several variants were discovered. One of the first of defined in terms of uniqueness of the marker and
these was Al Naskapi that was found in an Indian degree of polymorphism, and on both measures, Gm
group in Quebec (Melartin and Blumberg, 1966). Al scored highly.
Naskapi was subsequently observed in other
Canadian and US North American Indian samples,
for example among the Dogrib Indians (Szathmáry
HAPTOGLOBINS
et al., 1983).
Mode of inheritance: Autosomal codominant alleles, Hp1, Hp2.
Haptoglobins (Hp) bind free hemoglobin (Hb) that is

GROUP SPECIFIC COMPONENT (GC) released from destroyed red blood cells. The Hp-Hb
complex both prevents loss of hemoglobin from the
Mode of inheritance: Two common autosomal codominant
body through excretion, and also apparently plays a
alleles.
role in reducing the risk of bacterial growth by hemo-
Group specific component (Gc) is also found on globin (Eaton et al., 1982). Smithies (1955) was
chromosome 4 in close linkage with albumin. Its dis- the first to demonstrate polymorphic variation in hap-
covery was made by Hirschfeld (1959). Gc is well- toglobins by using starch gel electrophoresis. Hapto-
understood to be a vitamin-D binding protein, with globin has since been mapped to the short arm of
two common alleles, Gc1 and Gc2. From this function chromosome 16. As with other serum proteins, hapto-
it might be expected there could be some interplay globin variants could be under selective forces that
between Gc variants and the role of vitamin-D in blood maintain polymorphic frequencies depending on envir-
cell formation, particularly in people subject to becom- onmental stressors. For example, Hp1, which has a
ing anemic and in areas of reduced sunlight where higher hemoglobin-binding capacity than Hp2, gener-
human groups are at higher risk of rickets. With ally reaches its highest frequency in tropically located
respect to the latter prediction, Gc2 was thought to be African and Amazonian populations who face a high
more efficient in transporting vitamin D, and did show parasitic load and corresponding increased risk
a higher frequency in some northern populations, but for anemia.
218 Robert J. Meier
TRANSFERRIN calcification, and in maintaining an acid-base balance.

Early population studies did not reveal very much
Mode of inheritance: Three autosomal codominant variants, TfC variation except in Australia, with regard to CA I, and
is common, and TFB and Tf D are rare. Africa, in terms of CA II, which showed polymorph-
isms (Roychoudhury and Nei, 1988). Given the many
Transferrin, as its name implies, is iron-binding pro-
more recent discoveries of loci controlling the carbonic
tein that carries iron from the intestine and elsewhere,
anhydrases, there is the potential of finding addition-
and delivers it to active tissues and dividing cells. As
ally interesting population variants.
was the case for haptoglobins, Smithies (1958) dis-
covered the polymorphic status of the transferrin
locus, now mapped to chromosome 3. Could selection
be maintaining the polymorphism? Transferrin vari- GLUCOSE-6-PHOSPHATE DEHYDROGENASE
ants might be implicated in persons or groups chronic- (G6PD) DEFICIENCY
ally stressed by iron-deficiency anemia or who are at
Mode of inheritance: Multiple codominant X-linked alleles.
high risk for red blood cell destruction. Also, transfer-
rin may be involved with removing harmful allergens Glucose-6-phosphate dehydrogenase (G6PD) is per-
present in serum. While these are bases from which haps the most recognizable enzyme in anthropological
selection could operate, there was no clear evidence study when it appears in one of several variants that
that this has been the case. result in reduced enzyme production or a deficiency.
Its deficiency has received a high level of attention due
to its interaction with malarial sensitivity and resist-
ENZYMES ance, and hence, demonstrated increased frequencies
in groups residing in endemic malarial regions. This
Human variation in enzymes formed a vital area of topic will be discussed later. The normal functioning
research for anthropology/human biology, leading to G6PD enzyme plays an important catalytic role in
field studies among non-Western populations in the maintaining red blood cell membrane integrity. The
1960s. The most obvious interest, and of most clinical enzyme is found throughout most of the body includ-
significance, were enzyme deficiencies commonly ing skin and saliva. Its genetic control is located on the
known as inborn errors of metabolism. Several trad- long arm of the X-chromosome.
itional biochemical markers were identified, Table 13.2
lists a selected sample. A brief introduction to these is
provided here, that will be followed later by a descrip- HEXOSAMINIDASE A (HEXA) DEFICIENCY
tion of how these markers varied among different
populations, and some discussion of possible bases Mode of inheritance: Multiple codominant autosomal alleles.
for the variation. As in the case of serum proteins, Hexosaminidase A (HEXA) is example where an
electrophoresis was the then appropriate method of enzyme deficiency can have profound effects. The
investigating enzyme variants in the 1960s. When first mutated HEXA gene causes a lethal condition known
established as hereditary markers, enzymes were pro- as Tay–Sachs disease. Persons having the classical form
moted as prime examples of the “one gene-one protein” of Tay–Sachs disease experience developmental retard-
notion that had to be modified after subsequent dis- ation and neurological degeneration in early infancy
coveries, as with the G6PD locus that has numerous and in most cases die before reaching their third birth-
variants all due to mutations of one structural gene. day. A normal functioning HEXA gene, located on
chromosome 15, produces an enzyme that catalyzes
the degradation of excess ganglioside (a constituent
CARBONIC ANHYDRASE of cell membranes), whereas the mutated variant
allows for the build up of ganglioside in neurons that
Mode of inheritance: Two linked loci on chromosome 8, CA I causes the neurodegenerative disorder. Given the
and CA II, each segregating dominant alleles, along with mul- dire outcome for children with Tay–Sachs, it was sur-
tiple recessive variants. Current status is that there now are at prising that the condition showed such a high frequency
least 12 carbonic anhydrase loci, some linked and others on
in Ashkenazi Jews of Eastern Europe. Homozygote
several different chromosomes.
recessives did not survive childhood so the variant
Second only to hemoglobin, carbonic anhydrase forms marker would be expected to exist at a very low fre-
a large portion of red blood cell protein. Its major quency. Initial thinking proposed that random drift
function is to release carbon dioxide in the lungs in had by chance elevated the mutant HEXA enzyme in
conjunction with the respiratory cycle. Carbonic anhy- the comparatively small and separated Jewish commu-
drases also play a role in bone resorption and nities (Fraikor, 1977). Later, heterozygote advantage
was invoked as a possible contributing explanation readily diagnosable and is routinely tested for as part
(Chakravarti and Chakraborty, 1978; Marks, 1995). of newborn screening, and is preventable through care-
It was argued that overcrowded urban ghettos posed ful and consistent dietary management following a
severe risks for infectious diseases, for example, phenylalanine-free regimen at least through childhood.
tuberculosis, but heterozygotes were somehow pro- Like lactase deficiency noted above, PKU is another
tected. A similar argument will be noted later case of environmentally dependent or culturally medi-
with respect to cystic fibrosis. In a more recent report, ated expression.
the pendulum has swung back to explaining elevated
HEXA gene frequencies as due to drift in the form of
founder effect within a population experiencing rapid OTHER MARKERS
census growth (Frisch et al., 2004).
This section concludes with a description of variable
human conditions or traits that were included occa-
LACTASE DEFICIENCY sionally in population studies (see Table 13.2). Of inter-
est, investigations of phenylthiocarbamide (PTC)
Mode of inheritance: Autosomal alleles with lactase persistence polymorphism were even extended to nonhuman pri-
dominant over lactase deficiency. mates. Methods of study were quite different ranging
Yet another example of an enzyme deficiency, but with from visual and tactile examination for cerumen
comparatively low adverse consequences, involves lac- (ear wax) types, initially a host of clinical diagnosis
tase, a digestive enzyme of the milk sugar lactose. The and laboratory tests for cystic fibrosis that now include
lactase locus has been mapped to chromosome 2. genetic analysis, and serial dilution or simple test
Nearly all human babies produce sufficient amounts paper strips for the PTC-tasting trait. They also show
of this enzyme throughout their growing years, and a range of consequences for the individual from being
then undergo a decline of enzyme output into matur- rather benign for cerumen types, to profoundly
ity. Milk, and unfermented derived milk products, affecting the well-being of cystic fibrosis patients.
causes these adults to experience unpleasant digestive
symptoms, including bloating and diarrhea. Yet adults
in some parts of the world continue to produce higher CERUMEN (EAR WAX) TYPES
amounts of lactase, and hence have none of the afore-
Mode of inheritance: Allele for wet, sticky ear wax is autosomal
mentioned symptoms. Population studies showed a
dominant; dry ear wax is recessive.
strong association between cultures that had a long
tradition of dairy farming and a persistence of lactase Cerumen markers are expressed as wet (sticky, brown)
into adulthood. A genetic analysis based on family and dry types (flakey, light colored) that are controlled
studies demonstrated that lactase deficiency was by a locus on chromosome 16. There is human popula-
inherited as an autosomal recessive, meaning that het- tion distribution variability in these types along with
erozygotes and homozygotes possessing the dominant implications of selection acting on ear wax type relative
marker were lactose tolerant (Sahi, 1974). This was a to climatic variables. The dry type is most often found
classic example of a biocultural interaction. It also in northern Asian populations, while the wet type
illustrated how environmentally dependent gene is found in tropically located Asians, as well as in
expression was, or that genetic predisposition required Africans and Europeans. Whatever adaptive signifi-
suitable conditions to become of significance to the cance there is for ear wax type polymorphism is yet to
organism. be determined.
PHENYLALANINE HYDROXLASE (PAH) CYSTIC FIBROSIS

DEFICIENCY
Mode of inheritance: Multiple autosomal alleles, with CF
Mode of inheritance: Autosomal alleles, with PKU recessive. recessive.
Phenylalanine hydroxlase (PAH) is a catalytic enzyme Cystic fibrosis (CF) is a debilitating condition that dis-
that participates in the conversion of phenylalanine rupts normal pancreatic, intestinal and respiratory
to tyrosine. A deficiency of PAH is an inborn error functioning. After some intensive genetic research,
of metabolism that can lead to varying degrees of the CF gene was mapped to chromosome 7 in 1985.
impaired mental functioning, and other pleiotropic Since affected individuals prior to more recent therap-
effects, known as phenylketonuria (PKU). The mutated ies were at high mortality risk as children and had
allele is located on chromosome 12. Phenylketonuria is reduced fertility as adults, it was puzzling why the
220 Robert J. Meier
condition had reached a high frequency in some Schanfield and Fudenberg (1978) and Schanfield
European populations. A possible answer may be (1980), that dealt with the Gm and HLA systems and
found in an association between the CF locus and risk accompanying extensive tables of marker frequencies
for tuberculosis, paralleling heterozygote advantage for world populations. Schanfield (1980) also notes a
explanations given for Tay–Sachs disease, and also general problem in that certain markers could not be
for sickle cell anemia which will be discussed more studied routinely because their reagents were not read-
fully later in the context of balancing selection and ily available, with particular reference to the HLA
diseases. system.
Now that a set of classic markers has been intro-
duced, the next section will offer a discussion of how
these markers were applied in various contexts, the
PTC TASTING first being that of describing human biological diver-
sity, including its most contentious application, that of
Mode of inheritance: Taster allele is autosomal dominant; non-
classifying human races.
taster is recessive; variable expressivity in phenotypes.
The ability to taste the compound phenylthiocarba-

mide (PTC) is controlled by a major gene mapped to BLOOD GROUP MARKERS FOR CLASSIFYING
chromosome 7, with another locus likely involved as HUMAN POPULATIONS
well. For an up-to-date confirmation of PTC chromo-
some mapping see Drayna et al. (2003) and for a com- There is a long and tortuous history surrounding
plete historical review of this trait see Wooding (2006). unsuccessful attempts to sort human populations into
Although a rigid bimodal distribution of tasters and stable, mutually exclusive categories called races.
nontasters is not observed, especially with applying Rather than extensively review that history here, the
the serial dilution procedure, there is a certain ease in reader is referred to these works for that information
collecting results, apparently so readily accessible that (Montagu, 1964; Marks, 1995; Brace, 2005; Molnar,
chimpanzees and rhesus monkeys became suitable 2006). It is important, however, to trace the use of
subjects (Eaton and Gavan, 1965). Roychoudhury and blood group markers as these became available to
Nei (1988) list nearly 80 human studies that had those choosing to carry out race classification. That
carried out PTC testing that virtually covered the story, as already mentioned, began with the discovery
world. Gene frequencies were highly variable both by Landsteiner in 1900 of the ABO blood group. A little
within and between continental samples, with no dis- more that a decade later, the ABO group was being
cernible patterns. There has been a suggestion of an studied by Ludwik Hirschfeld by conducting sero-
interaction between dietary practices and thyroid func- logical tests on thousands of persons, soldiers and
tion (Molnar, 2006). PTC, as a synthetic compound, civilians, from throughout Europe and even some
serves as a proxy for a carbon-nitrogen-sulfur radical from China, Japan, and Africa (Mourant, 1983). His
found in certain plant foods, particularly those of the results laid the groundwork for all subsequent studies
cabbage family, that tasters perceive as bitter, and showing serological distinctions across human popula-
hence, to be avoided. This could be a protective behav- tions, that is, the establishment of racial divisions.
ior in that cabbage and its relatives may block the The premise applied was quite straightforward.
uptake of iodine, thereby reducing thyroid function, First, accepting that the ABO blood group markers
and resulting in depressed metabolism that in turn were inherited (which Hirschfeld helped to show),
affected childhood growth and adult fertility. Con- then frequencies of ABO blood group types (and later
versely, nontasters have been shown to be more sus- calculated gene frequencies) would indicate the
ceptible to developing nodular goiters, presumably due degree of relationship between populations, the more
to a reaction of the thyroid gland to depressed amounts similar they were the more closely they were related to
of iodine in the diet. Additional testing of the role each other, and vice versa. From there it was a matter
selection and adaptation play in maintaining the PTC of drawing lines between blocks of populations, a step
polymorphism seems warranted. that undoubtedly was greatly aided by geography and
In concluding this section on basic marker identifi- continental boundaries, and taken by Hirschfeld
cation, it should be pointed out that not all population and his wife (Hirschfeld and Hirschfeld, 1919) in
studies utilized all of the markers described, or for that their defining of three ABO racial types, European,
matter, had necessarily restricted their research to Asio-African and Intermediate (Marks, 1995). This
those that appear above. On the first point, research was followed by other attempts at serological race
projects added markers as they were discovered and classification (Ottenberg, 1925; Snyder, 1930; Wiener,
found to be anthropologically useful. As noted earlier, 1948), but the effort that might have had a high poten-
usefulness of markers was well investigated in tial for impacting anthropological thinking on races
was that of Boyd. In his book, Genetics and the Races of What helped to replace racial classification were
Man: an Introduction to Modern Physical Anthropology attempts to discern the nature of human population
(1950), Boyd set forth in highly explicit terms why he relationships in terms of cultural historical and micro-
considered blood group markers to be more scientific- evolutionary processes. An even more basic task was to
ally sound for racial classification than that any of be able to accurately analyze whatever biological dif-
the heretofore used methods utilizing morphological ferences existed between groups without any need to
characters, including anthropometry. classify them. A study from Boyd’s time period that
When Boyd’s work was published, blood group fre- illustrates this kind of endeavor was done by Sanghvi
quencies were available in large samples for the ABO, (1953). He included five endogamous Indian castes in
Rh, and MN systems. In addition, Boyd added PTC an analysis of anthropometric versus genetic markers
tasting and secretor status to his set of markers. to discern their relationships. His list of markers, cer-
His genetically defined races largely matched earlier tainly short by subsequent standards, only consisted
classifications, particularly that of Wiener (1948). of ABO, MN and Rh blood group phenotypes, taste
Not surprising then, Boyd’s genetic races conformed reactions to PTC, and red-color-blindness. He con-
closely with geography, a point that he seems to regard cluded that either the genetic or morphological method
as confirmation of what he expected to find regarding could be more useful in reflecting biological relation-
human population descent histories and their patterns ships in certain cases, but more likely they will comple-
of separation and migration. His claims for the advan- ment each other, and hence, both should be applied
tages of the genetic method over earlier classifications using many more measurements and markers than he
are that it is more simply done, completely objective, did. We will see in the next section that this recommen-
and that gene frequencies do not have the genetic dation is indeed heeded within a decade with the
uncertainty that is hidden in phenotypic traits, and launching of a number of major research projects.
gene frequencies provide quantitative rather than Physical anthropology apparently was not so con-
qualitative measures of population differences along vinced of Boyd’s approach not because it applied
with an assessment of admixture (Boyd, 1950). genetic markers, but because they were used to classify
It should be noted that the erroneous claim of selective races. Two principal textbooks of roughly that time
neutrality for blood group genes initially was accepted period perhaps best reflect the state of affairs.
by Boyd (1950), except for maternal–fetal incompati- Montagu (1960) and Buettner-Janusch (1966) both
bility in the Rh system, who then later abandoned it are replete in their coverage of genetic markers, com-
(Boyd, 1963a). plete with tables of gene frequencies and allele distri-
In this same year, Boyd (1963b) touted what he bution maps for the world. Beyond that they provided
judged to be major accomplishments of the genetic clear background information on the modes of inherit-
method. He concluded that genetic methods had con- ance and methods for identifying blood groups and
tributed to physical anthropology by: (a) confirming an serum proteins, and most importantly, what was then
Indian origin of Gypsies; (b) providing a quantitative known about the selective basis of certain systems,
assessment of white admixture in American Blacks; (c) such as the association of blood groups and diseases
establishing that Lapps were a distinctive European and the anthropological significance of hemoglobin
race; and (d) showing that Papuans of the New Guinea variants at the sickle cell locus. Race classification
region were native to the South Pacific and had not utilizing genetic markers was seen as relatively unim-
migrated from Africa. With regard to one of these pre- portant and unproductive, in comparison with the
sumed feats there is recent caution expressed against study of selection and other microevolutionary pro-
the use of markers, sometimes single alleles, for calcu- cesses that occurred within local populations. On a
lating degree of admixture (O’Rourke, 2000). larger scale, research interest shifted to investigating
By the time of Boyd’s 1950 classification of sero- how and when gene pools across and between contin-
logical races, it had already been reported (Boas, 1912; ents came to differ from one another, again through
Shapiro and Hulse, 1940; Lasker, 1946) that head and microevolutionary processes. This state of affairs
body measurements were subject to modification in undoubtedly reflected the paradigm change that
children of migrants who accommodated to new envir- Washburn (1951) had proposed a decade or so earlier
onmental conditions. Hence, this important finding that the “new Physical Anthropology” should empha-
would severely question the presumed stability of size an understanding of function and process as
those variables, such as the cephalic index, that had opposed to an earlier focus on technique and descrip-
been so heavily relied upon by race classifiers. How- tion as a direct goal.
ever, by the end of the 1960s, race classification itself In opposition to race classification, a mid-twentieth
was on the wane, and genetic markers were not able century alternative was to view patterns of genetic
to sustain efforts that sought to arbitrarily apportion variation expressed in terms of clinal distributions.
human variation into discrete categories. Gene frequency clines joined the already recognized
222 Robert J. Meier
0 500 ml
0 500 km
0.000–0.049 0.350–0.399
0.050–0.099 0.400–0.449
0.100–0.149 0.450–0.499
0.150–0.199 0.500–0.549
0.200–0.249
0.250–0.299
0.300–0.349
13.1. Frequency of the A1 allele showing a clinal distribution in Australian groups.
From Birdsell (1993). # 1993 Oxford University Press, reprinted with permission.
gradients in human morphological variation with a smooth and steady transition across Eurasia. There
respect to body size and shape (Allen’s and Bergmann’s were gaps in the big picture, and very likely if B-allele
Rules), and skin pigmentation (Gloger’s Rule). These frequencies were filled in, a more detailed map com-
so-called “ecogeographic” rules generally explained posed of many local-level populations would show
clinal variation in morphology as due to adaptive some breaks or even reversals of the general geo-
responses of populations residing in gradients of tem- graphic trend. It is to be expected that there were
perature, solar radiation, and other environmental historical episodes involving small founder groups that
conditions that occurred in latitudinal changes. It was became isolated over sufficient amounts of time for
reasoned that gene frequency clines, or genoclines, genetic differentiation to have occurred. Lastly, gene
might also be the result of natural selection gradients, flow and human population movements were not
such as levels of disease stress, but could as well be exclusively in a westerly direction.
explained by actions of gene flow, migration, and For a more recently plotted example of a cline also
human mobility and settlement patterns. For here, a from the ABO system, Figure 13.1 shows A1-allele fre-
classic example of a genocline will be presented quencies as isogenes (comparable to isotherm contour
followed by a more recent application of genocline lines connecting points of equal temperature) for the
based on Australian data that had been collected Aboriginal Australian population (Birdsell, 1993).
decades earlier (Birdsell, 1993). The overall range in frequency for A1 is from a high
A textbook example of a genocline is the distribu- of 0.53 near the center of the continent to a minimum
tion of the B allele of the ABO system as its frequency of 0.03 at the coastal and northern island areas. As
was mapped from eastern Asia to the British Isles. would be expected there are some steep declines along
Although it was not known why, the B allele had its with more gradual gradients in the topographic dis-
maximum frequency in Asia at around 25% but then play. Birdsell pointed out a generally recognized prem-
declined to less than 5% in much of Western Europe ise that single genes, such as the A1 allele, more rapidly
(Mourant, 1954). A likely explanation for the B-allele respond to microevolutionary processes than poly-
cline rested in historical migrations and invasions of genic traits. Accordingly, in reviewing the history of
peoples from Asia westward over the past couple of human occupation of Australia, he attributed the gene
millennia. To be sure, the B-allele cline was not exactly frequency distribution shown in Figure 13.1 to be the
product of settlement of small founding groups (that is, comparative findings for the Solomon Islands as well
founder effect), successive major migration waves, and as with additional samples that had been obtained
importantly, a population structure of local bands earlier from Bougainville (Friedlaender, 1975), and also
within a larger tribal population. samples from a broader Pacific Island context. The
Clinal distributions of classic markers, such as upshot of this aspect of the study that involved markers
those for the B and A1 alleles just described, clearly was a complex and not easily discernible pattern of
demonstrated that race classification could not begin genetic variation, but it seemed to indicate at each level
to capture the complexities and details of human from local groups to that of Pacific region and even
population relationships and historical connections. beyond, that biological heterogeneity and variability
In pursuit of that goal, the discussion now turns to extended deep into history and could not be explained
population studies that set out to reconstruct history simply by random drift of small, isolated groups.
through an understanding of microevolution. Another aspect of the Solomon Islands Project,
which also was carried out in many other research
efforts in that time period including the earlier
APPLICATION OF MARKERS TO POPULATION Bougainville study, was to incorporate genetic markers
STUDIES AND MICROEVOLUTIONARY with multiple measures of distance as a test of corres-
PROCESSES pondence between these measures for potentially real-
izing the same or similar outcomes of population
Dynamic population study took precedence over static relationships. In this regard, the Solomon Islands
race labeling with the launching of a number of Project combined the distance measures of geography,
important human biology field research projects. One language, anthropometry, odontometrics, dermato-
such effort was the Harvard Solomon Islands Project glyphics, as well as the set of genetic markers noted
that was conceived by Albert Damon in the early 1960s earlier. One of the more enlightening results showed
(Friedlaender, 1987). This project served as a model of that genetic markers, along with anthropometrics
design for many more similar projects that were under- and odontometrics, less closely corresponded with
taken in roughly this time period. The Solomon Islands language and geography than did dermatoglyphic
Project applied a multidisciplinary approach in which variation (Friedlaender, 1987).
all four subfields of anthropology were represented, Other studies have yielded varying results in these
along with specialties from the biomedical sciences. distance correspondence analyses. A brief review of
It was reasoned that if population processes were this matter can be found in Meier (1980), who noted
to be adequately understood, it would be necessary to that incongruence between distance measures could be
examine essential aspects of human behavior and deci- due to such factors as sample size and composition,
sion-making. This meant that culture interacted with number and kinds of markers used, and level at which
human biology, and in recognition of this connection a the analysis is done, from local villages to large regions.
biocultural or biobehavioral approach was established. For this discussion of genetic markers, it is perhaps
A clear illustration is to be found in population genetic best summarized with the appreciation that Mendelian
measures of migration or gene flow, and even in selec- traits could well be subjected to short-term and rela-
tion and random drift. The strength of these processes tively rapid change in frequency via random drift and
very much depended upon human behavior and deci- founder effect (particularly in small, semi-isolated
sion-making, such as cultural expressions in settlement groupings), but also undergo successive generational
patterns, mate choice and marriage customs, and cul- change due to selection processes. And hence, there is a
turally derived medical systems for diagnosis and great need to understand the nature and makeup of the
treatment. sample upon which the marker frequencies are based,
A major task within the sphere of population genet- and to fully characterize samples even though most
ics in the Solomon Islands Project was to map bio- often there was little way to control sample makeup
logical variation among several groups on different while conducting field studies. In the end, there
islands with an aim to portray relationships of these remains considerable theoretical uncertainty whether
groups in terms of microevolutionary processes, espe- the degree and rate of change in frequencies of
cially those pertaining to selection, random drift, and markers are expected to correspond well with the other
migration (Rhoads and Friedlaender, 1987). Among distance measures, such as anthropometric or lan-
the markers included in that study were numerous guage change. On this matter, Lewontin remarks in
blood polymorphisms, namely; eight red blood cell his Foreword to Friedlaender (1975) that linguistic dis-
antigen systems, haptoglobins, transferrins, and tance at that time was too simply measured. However,
Gm and Inv systems. Calculated allele frequencies Lewontin praised Friedlaender’s work for its strong
from these markers were used in a distance analysis emphasis upon the historical perspective, that is, in
and other multivariate procedures that rendered reconstructing the action of evolution over time.
224 Robert J. Meier
Several population studies in the late 1960s and TABLE 13.3. Selected population studies employing
into the 1970s paralleled portions of the Bougainville classical markers.
and Solomon Islands Project design, particularly for
Study area/population Year begun Reference
their application of the multidisciplinary, biocultural,
and historical approaches. One set of such studies can Wales Post-WWII Harper and
be grouped under the International Biological Pro- Sunderland
gramme (IBP) Human Adaptability Projects. For a (1986)
brief background, the IBP was composed of seven Australia 1952 Birdsell (1993)
sections that directed a global effort toward measuring Canada/Blackfeet 1952 Chown and Lewis
Indians (1953)
and understanding ecological productivity and its
Brazil/Xavante 1962 Neel et al. (1964)
interaction with human welfare. One of these sections
was that of Human Adaptability (HA) which got under- South Africa/San, 1963 Jenkins et al. (1978)
Herero, and others
way in the mid 1960s. Relevant to this discussion,
Easter Island* 1964 Etcheverry (1967);
methods for collecting specimens, such as blood from
Meier (1969)
which markers could be determined, were presented in
Peruvian Andes/ 1965 Baker and Little
the IBP HA Handbook that first appeared in 1965 Quechua (1976)
(Weiner and Lourie, 1969). This guide did not specify India/Gavdas 1966 Malhotra (1978)
which markers were to be studied but rather set forth Japan/Ainu 1966 Omoto (1978)
specifics of proven field methods for securing, storing,
Bougainville 1966 Friedlaender (1975)
and transporting specimens so that they could be com-
Solomon Islands 1966 Friedlaender (1987)
parably analyzed, very often in a distantly located
Alaska/Eskimos 1967 Jamison et al.
laboratory. A common problem was hemolysis during (Inupiat)* (1978)
extended periods of travel, rupturing the red blood Southwestern United 1967 Niswander et al.
cell membrane and spilling out constituents that would States/Papago (1970)
have been used for serological testing. The IBP Saharan Africa/Ideles 1968 Lefevre-Witier and
Handbook also detailed procedures for carrying out Verges (1978)
field testing of some markers, for example screening Mexico/Tlaxcaltecan 1969 Crawford et al.
methods for G6PD and determining PTC taster status. (1974)
A major concern that needed to be addressed was Central America/Black 1975 Crawford (1984)
that of reliability of the serological results even when Caribs (Garifuna)
the specimens reached their destinations presumably Canada/Dogrib Indians 1979 Szathmáry (1983)
intact. This matter had received some attention at Note: *Due to problems, complete serological testing could
the time. not be done on the Easter Island and Inupiat blood specimens.
Osborne (1958) had reported some major discrep- WWII, World War II.
ancies for blood group testing when done at three well-
established laboratories. Handling problems may have
been an issue in another study documenting testing the greatest emphasis on applying classic markers to
discrepancies (Livingstone et al., 1960). The least population genetics questions (Neel and Ward, 1972).
stable systems involved subtyping of A in the ABO These along with a selection of additional field studies
system, and in the Duffy and P markers. Thus, it was appear in Table 13.3.
imperative that blood specimens at the very least be Particular mention should be made here of a four-
handled with the utmost care to avoid degradation volume series published under the topic of
problems. One study that did a careful analysis of such Anthropological Genetics (Crawford and Workman,
problems was Neel et al. (1964) in which they had 1973; Mielke and Crawford, 1980; Crawford and
carried out field testing on blood specimens collected Mielke, 1982; Crawford, 1984). (A fifth volume in this
from the Xavante of Brazil, and then later retested series-Crawford, 2007, presented an updating of the
them in their laboratory in Ann Arbor, Michigan. earlier volumes by focusing upon molecular genetics.)
According to their full disclosure, discrepancies These works in general illustrated how useful classical
seemed to relate to different testing and laboratory markers were in population study, for example of
conditions, and it was these problem areas that the the Black Caribs of Central America (Crawford, 1984).
IBP Handbook had hoped to rectify. This volume contained several differently authored
Under US IBP/HA auspices, multidisciplinary field chapters devoted to marker description and frequency
studies that included a survey of genetic markers distributions and then went on to explore critical
were carried out among human groups residing in topics that employed these data in such matters as
Alaska (Inupiat Eskimos), Peru (Quechua), and Brazil admixture estimates, fertility differentials (in the case
(Yanomama and Makiritare), with the last cited having of the sickle cell locus), and population structure.
70
65
60
55
50
45
40
35
30
–20 –10 0 10 20 30 40 50
13.2. Synthetic map of Europe and western Asia based on first principal component (PC). The range
between the maximum and minimum values of the PC has been divided into eight equal classes.
From Cavalli-Sforza, et al. (1994). # 1994 Princeton University Press, reprinted with permission.
It was these kinds of studies done on regionally A commonly applied procedure for depicting popu-
demarked human groups for which genetic, biological, lation relationships that was based on classic markers,
and cultural information could be combined that offer and continues to be used with molecular data, was that
sharp insight to microevolutionary processes and of dendrograms or phylogenetic trees. An example of a
population dynamics. dendrogram is shown in Figure 13.3. Various statistical
However, there was also the big picture to deal methods were employed to generate graphically clear
with, that is, the relationships of neighboring popula- representations of genetic similarities or the opposite,
tions as well as those that were distant in both geog- genetic distance among populations. There generally
raphy and in their historical connections. The work was no unique solution in reconstructing trees; hence,
that epitomizes this effort was that of Cavalli-Sforza multiple trees could lead to alternative interpretations.
et al. (1994). If this tome can be described briefly, it is However, dendrograms, and also synthetic maps,
best depicted as a worldwide geography of human could be viewed essentially as methods for reducing
genes. As customary for physical geography, there are large data sets into manageable entities that might in
numerous maps that depict levels of gene frequencies fact partially answer questions concerning population
for the major continents and Oceania. These are affinities or perhaps even more importantly, point
referred to as synthetic maps for their handling of an future research toward productive, new directions.
array of genetic markers by a multivariate procedure, The final work to cover in this section on popula-
namely, principal components (PC) analysis. An exam- tion study is a review that addressed the thorny ques-
ple of a synthetic map is found in Figure 13.2. tion of peopling of the New World through a
These maps then are interpreted in light of histo- congruence of variables approach (Greenberg et al.,
rical and microevolutionary processes whereby simila- 1986). They included linguistic, dental, and genetic
rities and differences in PC values (seen as peaks and lines of evidence in an attempt to reconstruct the
valleys on the maps) can represent migrational or timing and number of migrations. This work is cited
selection patterns, sometimes according to gradients because it stands at the transition between the use of
or clines, but possibly on a more local level show sharp classical markers and the then newly developing DNA
breaks due to population isolation and random drift. technology, at that time devoted primarily to
Synthetic maps of this sort also were constructed from restriction fragment length polymorphisms (RFLPs).
classic markers about a decade earlier for North An extensive list of references can be found in the
American Native populations (Suarez et al., 1985) that article. These are mostly dated from the late 1970s to
assisted in sorting out population relationships and the mid 1980s that include original study results for
migration patterns. Native New World populations with respect to blood
226 Robert J. Meier
San (Bushmen)
Mbuti Pygmy
Bantu
Nilotic
W.African
Ethiopian
S.E. Indian
Lapp
Berber. N. African
Sardinian
Indian
S.W. Asian
Iranian
Greek
Basque
Italian
Danish
English
Sarnoyed
Mongol
Tibetan
Korean
Japanese
Alnu
N.Turkie
Eskimo
Chukchi
S. Amerind
C. Amerind
N. Amerind
N.W. American
S. Chinese
Mon Khmer
Thai
Indonesian
Philippine
Malaysian
Polynesian
Micronesian
Melanesian
New Gulnean
Australian
13.3. A dendrogram or phylogenetic tree based on 42 populations. From Cavalli-Sforza, et al. (1994).
# 1994 Princeton University Press, reprinted with permission.
group, serum protein, and enzyme polymorphisms. The mathematical and theoretical emphasis. Later, by the
review of these markers concluded that genetics could 1940s, the modern synthesis of evolution was estab-
be complementary to the other two lines of evidence but lished with population genetics at its foundation.
could not stand alone in supporting a tripartite migra- While population genetics theory certainly received
tion history of New World settlement. This work also application to human groups over the next several
provides a critical sense of how researchers viewed the decades as noted above in population studies, it
claims of Greenberg et al. (1986) through multiple achieved a substantial boost with respect to the aca-
authored comments that directly followed the article. demic realm in 1971 with the appearance of the initial
edition of The Genetics of Human Populations (Cavalli-
Sforza and Bodmer, 1999). Three chapters in this later
GENETIC MARKERS AND SELECTION edition are most relevant to note here for their in-depth
treatment of classical markers with regard to maintain-
This section will focus on the role that classical ing polymorphisms (Chapter 4), possible adaptive rela-
markers played in assessing natural selection as a tionships of blood group antigens and serum proteins
major process for understanding genetic variation to selective agents, particularly disease and incompati-
within and among human populations. To some degree bility (Chapter 5), and marker frequency distributions
this development was imbedded in the history of popu- across groups (parts of Chapter 11).
lation genetics. During the 1930s Mendelian genetics In this last cited chapter the authors continued
interfaced with microevolutionary theory to form to espouse a race concept, definitely not in the pre-
population genetics that at that time had a strong vious manifestations of racial typology or strict
classification, but rather as an acknowledgement of historical and environmental conditions for selection
biological differences and similarities they assumed to operate on led to variation across different human
to be based on race. It appears that their use of race groups. This section will cover the use of markers
is simply a matter of convenience for defining popula- in trying to understand the nature of ABO polymorph-
tion units of study, which is to this day a vexing prob- isms with regard to selection.
lem for anyone carrying out population studies. Who The earliest work to implicate selection in the ABO
belongs within the sample and how will comparable distribution was faulty for its lack of statistical rigor.
study groups be defined? Island populations and semi- It simply amounted to collecting data showing associ-
isolated villages offer fairly clearly demarked boundar- ations between particular ABO blood types and a set of
ies, and this may in fact underlie part of the attraction diseases, often using hospital patient records as the
for the geographic selection in the field studies noted sampling source. However, flaws in the early research
above. were in not having adequate control groups or
In the manner in which Cavalli-Sforza and Bodmer unbiased samples that would allow any deviation from
(1999) had used race, it might have been more appro- normal expectations to be properly ascertained. Once
priate to have used a concept proposed by Montagu these study defects were corrected, many significant
(1964), the “genogroup,” which essentially defined associations remained with respect to noninfectious
population differences on the basis of gene frequen- diseases, but not nearly as clear as the results for infec-
cies. Then again, Montagu seemed to favor “ethnic tious diseases, and these will be discussed first.
group” as a substitute for race, which has gained Armed with these findings, it was important to now
fairly wide application. However, “ancestry” appears offer possible selective mechanisms that would
to be replacing all of these terms at the present account for the blood group and disease associations,
time in the context of DNA markers. Aside from con- and that then would define directions for further inves-
structing tree diagrams to show partial conformity tigation. Four categories of infectious disease had been
with prior race classifications, Cavalli-Sforza and identified as likely candidates for changing gene fre-
Bodmer (1999) more importantly demonstrated how quencies through natural selection (Vogel and
microevolutionary processes drove the course of popu- Motulsky, 1997). These were: (1) acute infections, such
lation change. Their text, then, established a formal as small pox, plague and cholera, that periodically
educational treatment from which to pursue interests spread as epidemics over large areas; (2) chronic infec-
in human population genetics. Needless to say, the tions that were highly contagious, such as tuberculosis
genes upon which most of the principles rested were and syphilis; (3) intestinal infections that afflicted all
classical markers. And it is a consideration of these age groups but were likely fatal to infants and younger
markers with respect to selection that is covered next. children; and (4) malarial infection.
These agents of selection would operate through
differential mortality and fertility, although for some
ABO MARKERS AND DISEASE ASSOCIATIONS of them the former would be more likely in that many
people would be stricken with the disease when they
As broader world surveys of the ABO blood-group dis- were past their prime reproductive years. In that situ-
tributions became available, it also became apparent ation, selection would not be acting directly on the
that gene frequencies varied both within highly reproductive success of the individual, but could have
polymorphic loci as well as considerably across popu- an impact on broader measures of fitness, e.g., inclu-
lations to a degree that could not be attributed to sive fitness, due to the loss of support and resources
newly arising mutation nor to random drift or to gene provided by postreproductive members of the society.
flow, at least above local population levels. This, of Differential survival in connection with the ABO
course, pointed to selection as the active force in blood groups was presumed to be an increased suscep-
both changing and in maintaining gene frequency tibility or resistance by virtue of certain markers a
levels. There was ongoing debate as to whether ABO person possessed. Accordingly, it was found that indi-
polymorphisms were in a stable state or transient viduals carrying the A antigen were more likely to
and hence subject to eventual loss of alleles. The argu- contract smallpox (Vogel and Chakravarartti, 1966),
ments for stability rested on the presence of the while persons with the O blood type were at higher
ABO blood group system in nonhuman primates – risk for cholera (Glass et al., 1985). It was presumed
antigens analogous to A and B are present in Rhesus that these blood types were in fact more susceptible
macaques (Duggleby, 1978), and the relatively narrow because of pathogen similarity to their own genetic
range of ABO gene frequencies within certain human makeup. Hence, there was a failure of their immune
groups. These lines of evidence indicated that ABO system to recognize the foreign invader, likely a bacter-
polymorphisms had a long history by virtue of their ium or virus, and consequently did not initiate an
existence in nonhuman primates, and then varying appropriate defense response that then resulted in an
228 Robert J. Meier
TABLE 13.4. Significant associations between ABO markers and noninfectious diseases.
Diagnosis No. of series No. of patients No. of controls Markers compared Mean relative incidence*
Cancer, stomach 101 55 434 1 852 288 A:O 1.22

Cancer, colon 17 7 435 183 286 A:O 1.11
Cancer, pancreas 13 817 108 408 A:O 1.24
Duodenal ulcer 44 26 039 407 518 O:A 1.35
Gastric ulcer 41 22 052 448 354 O:A 1.17
Source: Data taken from Vogel and Motulsky (1997, p. 221).

*Relative incidence is calculated as the ratio of, for example, A:O patients divided by A:O controls.
increased mortality risk. Highly relevant supporting that the ABO blood group and secretor status of indi-
evidence for this position came out of India for viduals may in fact be part of an evolutionarily derived
its comparatively high frequency of the B allele that innate immunity against infectious diseases (Lindén
could be explained by that country’s long history of et al., 2008).
smallpox and cholera epidemics, that would render When considering noninfectious disease associ-
both the A and O markers at a selective disadvantage ations with ABO, the list is much longer and statistic-
(Buchi, 1968). Conversely, over many generations per- ally stronger but an understanding of the mechanism
sons carrying the B antigen had a proportionately responsible was, and still is, virtually unknown.
higher survival rate that boosted the frequency of this Table 13.4 provides a selected sampling of significant
marker. associations. These represent some of the largest
Population and biomedical studies of these, and samples of patients and controls from worldwide
other blood group and infectious disease associations, series, and undoubtedly established the statistical real-
have yielded varying and inconsistent results uphold- ity of ABO markers and disease associations. The
ing the immunological hypothesis to explain ABO dis- selected set focuses on the digestive system, whereas
tributions. A troubling matter is that different disease a more thorough listing would also include malignant
associations have been found for the same locus, which and nonmalignant conditions of the reproductive and
raises a question of what the statistical associations vascular systems. For the gastrointestinal tract, initial
actually demonstrate (Weiss, 1993). It does appear speculation was that there were differential immune
that selection acting in this manner through infectious responses by persons with different ABO antigens,
disease probably does explain some of the worldwide especially of the soluble form. This thinking would
marker frequency distributions. It has been reported parallel the proposal noted above for ABO associations
that testing of the immunological hypothesis was dis- and infectious diseases. Testing of this hypothesis,
continued sometime after the late 1970s (Vogel and however, is complicated due to the interplay in the
Motulsky, 1997). Yet, there is at least one area of gut between intestinal flora, highly variable dietary
research along this line that remains very active. practices around the world, and ABO antigen specifi-
During the 1950s it was shown that persons with blood cities. It has been concluded that the contribution of
type O were more susceptible to having stomach ulcers ABO polymorphisms to the etiology of digestive ail-
(Table 13.4). It was subsequently discovered that non- ments is quite small (Vogel and Motulsky, 1997), and
secretors of ABO substances were particularly vulner- further that, even though these markers cannot be
able. This was followed by the highly significant considered neutral, the low level and uncertain direc-
finding that Helicobacter pylori was closely associated tion of selection will not explain the maintenance of
with stomach ulcers, and that the attachment of this variation observed in the ABO distribution (Cavalli-
bacillus (bacterial infection) to the gastric epithelium Sforza and Bodmer, 1999).
was mediated by blood group antigens. In particular,
it was persons who carried the Lewis Leb antigen
that appeared to be most likely infected and thereby INCOMPATIBILITY SELECTION AND BLOOD
experienced an ulceration process (Boren et al, 1993). GROUP MARKERS
However, a later study done in an outpatient clinic was
not able to confirm this result (de Mattos et al., 2002), Another area of research interest that addressed
but it did convincingly match earlier findings of the question of the persistence of blood group poly-
H. pylori infection predominantly in patients with morphisms is that of incompatibility selection. Incom-
O phenotypes. The pendulum continues to swing as patibility refers to maternal/fetal situations where the
a very recent report that studied monkeys concluded mother would carry in her system antibodies against
red blood cell antigens found in her developing fetus. by losing D and d alleles equally, over time the rarer of
For example in the ABO system, an O mother would be the two eventually would be lost, and it was clear from
incompatible with a fetus having an AO or BO geno- many surveys the d allele was consistently at a lower
type. It is predicted under population genetics theory frequency. On the other hand, surveys also showed that
that ABO heterozygotes would be selected against, not only was the d allele not close to being selected out
ultimately leading to a loss of genetic variability, unless or anywhere near to a recurrent mutation rate, it
there are counter selective forces that favor heterozy- seemed to be maintained at a much higher frequency
gote survival. What these forces are for the ABO system than a simple selection against the heterozygote model
is not yet known but probably do implicate the would predict. There had to be circumstances that
mother’s immune system. were countering selection.
In the case of the Rh system, where incompatibility Two of these circumstances were noted above in
is prominent in some populations, a somewhat clearer that the first-born children of Rh incompatibility are
picture has emerged. This discussion will be centered not affected and that later developing fetus’ may not
on the Dd locus, since it was this marker that directly necessarily have HDN depending upon the state of
caused transfusion problems that then led to the dis- sensitivity or antibody titer of the mother. Added to
covery of the system, and later was shown to be a cause these is the segregation outcome of fathers who are
of death of newborns in the situation of an Rh-negative either DD or Dd, and of course the latter have a 50%
mother (dd) whose infant was Rh-positive (Dd). probability have contributing a d allele and thus a
The child of this incompatible Rh combination was at compatible Rh-negative child. There is also some evi-
risk for having erythroblastosis fetalis or hemolytic dis- dence that parents who lost a child to HDN tended
ease of the newborn (HDN) due to Rh positive anti- to over-compensate their loss by producing more
bodies (the small 7S gamma G type) crossing the homozygote dd children, thus increasing the d allele
placenta and into the fetus. frequency. There is a final explanation for why the d
Not all Rh-positive children born to Rh-negative allele is elevated beyond model prediction that interest-
mothers suffered from HDN. The explanation involves ingly involved mothers who had a double incompati-
several mitigating circumstances. First of all, Rh anti- bility with their fetus’ for both Rh and ABO systems.
bodies are not naturally occurring, an Rh-negative Maternal/fetal incompatibility in the ABO system
mother has to be exposed to Rh antigens in order to does result in HDN, but this occurs in a small percent-
stimulate her system to produce antibodies. This could age of overall potential circumstances. In another por-
have come through an improper blood transfusion, or tion of the ABO incompatible cases, say with an
much more likely, through carrying an incompatible O mother and an A fetus, as the baby’s red blood cells
fetus. Some of the fetus’ red blood cells can enter the enter her system they are quickly destroyed by her
mother’s system at the time of delivery, and thereby normally present anti-A antibody. If the blood cells
be present to stimulate her to later form antibodies. also happen to carry the Rh-positive antigen and hence
Obviously, an initial fetus is not affected because the are Rh incompatible, then the cells are destroyed
mother has not yet been “immunized” or sensitized before there is time for the mother to build Rh anti-
prior to the baby’s birth. Subsequent incompatible con- body. In effect, double incompatibility serves to protect
ceptions increase the risk for HDN as the mother’s subsequent fetuses from HDN, and, of course, it would
antibody titer is raised. There appears to be some vari- help to maintain a higher d allele frequency.
ation in women as to how many pregnancies are req-
uired to build antibody strength to the point of causing
HDN. For some time now medical intervention has HLA AND DISEASE ASSOCIATIONS
protected mothers from having HDN babies through
the administration of a prepared antiserum that des- From the early 1960s onward there has been increasing
troys any fetal blood cells that might have entered the anthropological interest in the application of the HLA
mother’s circulation during an incompatible pregn- polymorphisms to investigating population relation-
ancy with the result that she is not sensitized. On rarer ships and to the study of microevolutionary processes,
occasions, treatment has been in the form of exchange particularly selection. The HLA system has turned out
transfusions done either on the fetus or newborn. Prior to be highly useful in both regards. Certainly it is the
to medical advancement severe HDN was often fatal, most polymorphic system, and discovery of new alleles
and obviously a source of much personal grief. is still occurring. In Roychoudhury and Nei (1988)
In the scientific realm a different kind of concern population data were compiled for 5 HLA loci and a
was brought out by the observation that the frequency total of 89 alleles. Updating of HLA polymorphisms
of Rh-negative allele d was substantially higher than can be found at an online website – IMGT/HLA Data-
expected since all HDN children who were selected base –that currently reports nearly 2300 alleles for what
against were heterozygote Dd. This should mean that is now known as Class I HLA alleles. Even going back
230 Robert J. Meier
to the late 1980s, allelic variation was high both within Given this unfortunate outcome, it would be pre-
and between sampled regions. For example, the B7 dicted that the HbS marker should decline in frequency
allele ranged from 0.066 to 0.144 in several European ultimately to the level of a recurrent mutation rate
countries, 0.031 to 0.060 in Asian populations, and at the locus. However, in endemic malarial regions
an African sample yielded a frequency of 0.115 of Africa it was proposed that there were counter-
(Roychoudhury and Nei, 1988). Much of the variation selection forces that were helping to maintain the HbS
in HLA polymorphisms can be ascribed to populations allele frequency in the population when it was com-
that had undergone random drift and to population bined with the normal HbA allele. Balancing
movements and resultant gene flow. With regard to selection operated against both classes of homozy-
selection, an early and striking association was found gotes, the HbS/HbS (from sickle cell anemia) and HbA/
between B27 allele and ankylosing spondylitis (AS) in a HbA (from malaria), and there was selection for the
British study. It is now known that a vast majority of heterozygote HbA/HbS (protection from malarial
persons who have AS (which causes inflammation of morbidity).
the spine and other arthritic symptoms) possess the The malarial parasite Plasmodium falciparum,
B27 marker. However, the marker frequency varies carried by Anopheles mosquitoes, does not find a hos-
across ethnic groups, and indeed AS can also occur pitable cellular environment in the heterozygote to
even when the B27 marker is absent. Ankylosing spon- complete it normal life cycle. This heterozygote advan-
dylitis is part of a group of autoimmune diseases, tage (also called overdominance) meant that both HbA
where the body’s immune system fails and then makes and HbS alleles were being maintained at the same
antibodies against itself. time that they were being selected out, a process that
The B27 marker, along with numerous other HLA could lead to an equilibrium state, or balanced poly-
alleles, probably predispose their hosts to autoimmune morphism. The alleles would be equal to each other in
reactions as well as to infectious diseases at times as a frequency only if selection against each class of homo-
single allele but often in combination with other alleles zygotes was at the same level, which it is not. Selection
in the form of haplotypes. HLA haplotypes provide a is much more severe against HbS/HbS than it is against
clear example of linkage disequilibrium due to selec- HbA/HbA, so an equilibrium gene frequency would
tion. In one study, haplotype A1 B8 DR3 was present in occur with the HbA allele proportionately much higher.
nearly all hemophilic patients who showed a rapid This can be shown through the aid of some basic popu-
course of developing AIDS after they were inadvert- lation genetics using the concept of relative fitness.
ently treated with contaminated blood (Steel et al, Relative reproductive fitness (w) is calculated with
1988). Later research with HLA polymorphisms con- respect to specified genotypes HbA/HbA (AA), HbA/HbS
tinued to find important marker associations with both (AS), and HbS/HbS (SS) and their expected frequencies,
susceptibility to and protection against disease, as will if there was Hardy–Weinberg Equilibrium at the hemo-
be referenced in the final section of the chapter. globin locus. For a quick review, Hardy–Weinberg
Equilibrium of genotypic frequencies depends on there
being random mating at the locus in question and
SICKLE CELL LOCUS AND MALARIAL there being no evolution occurring at this locus.
RESISTANCE A further theoretical condition is that the population
being studied be infinitely large. In spite of this last
The marker that probably garnered the greatest never-to-be-realized requirement, the Hardy–Weinberg
amount of attention from anthropologists in the Equilibrium was regularly found at a number of blood
1960s was a hemoglobin variant, HbS, the sickle cell group loci, but not for the sickle cell locus due mainly
allele. HbS is a point mutation that results from a single to the action of selection.
nucleotide substitution on the b-chain from the normal Relative fitness for sickle cell-locus genotypes was
adult hemoglobin structure coded by the HbA allele. calculated by Allison (1956) who derived his data from
This mutation leads to one amino acid change in the a number of African populations. He set the heterozy-
hemoglobin molecule. There are a number of such gote fitness at wAS ¼ 1.00 (which would make it rela-
variants classed as hemoglobinapathies, and two of tively the most fit), and found that fitness for one
these, HbC and HbE, will be discussed later. homozygote was approximately wAA ¼ 0.80 and for
Persons who are homozygote HbS/HbS episodically the other it was wSS ¼ 0.20. These values would trans-
manifest sicklemia or sickle cell anemia due to mul- late into a 20% reduction in fertility for HbA/HbA
tiple cascading effects of crescent-shaped red blood parents and an 80% drop in fertility for HbS/HbS
cells that are prone to hemolysis and also prevent parents. Again through an application of population
blood from freely flowing through capillary beds. genetics calculations, over time it would be expected
In the absence of medical attention, severe attacks are that the frequency of the HbS allele would decrease
generally fatal. until it reached an equilibrium of about 0.20. Since
this frequency was found in some African populations, and into Asia and Europe. On a related research front,
it provided evidence for a balanced polymorphism. Volkman et al. (2001) have proposed that P. falciparum
However, some human population geneticists con- has a recent origin from a single common ancestor.
tinued to question whether the sickle cell locus was in a
balanced or transient state using the available evidence
on differential fertility and mortality, along with com- MALARIAL RESISTANCE FROM OTHER
puter simulation models to help predict the timing of MARKERS
equilibrium gene frequencies. In some African popula-
tions, HbS frequency appeared to be stable, as noted By the late 1980s, HbS was the hemoglobin marker for
above, but in other regions it was subject to change which most population data were available. Limited
(Livingstone, 1989). Complicating the picture was an results for HbC and HbE were beginning to show a
interaction between HbS and other hemoglobin vari- geographic distribution coinciding with malaria that
ants, especially HbC in West Africa, where one or the suggested that these too were adaptive in heterozy-
other marker was possibly being replaced. Added to gotes in providing resistance to this disease. As noted
this, the severity of malaria disease changed by region earlier, HbC may have been replacing HbS in West
and altitude, and in fact very much depended upon the Africa, while HbE showed a high frequency in south-
kind and intensity of certain horticultural practices. eastern Asia, where a hilly, forested habitat fostered a
Livingstone (1958) and other researchers proposed different mosquito vector of malaria. Southeast Asia
that as subsistence patterns of some African cultures presented its own set of intriguing research questions
shifted toward the clearing of once forested land for with respect to genetic protection from malaria. In this
farming activities several thousand years ago, this region, another kind of faulty hemoglobin, referred to
established a more suitable environment for mosquito as thalassemias, appeared to be interacting with HbE.
populations to flourish. As a consequence, the presence For some background, thalassemias are the result
of the malarial parasite was promoted and malaria of point mutations, usually nucleotide substitutions or
became a major disease stressor. This would set up small deletions in regulatory genes that interfere with
the next step in the malaria hypothesis that involved the normal synthesis of hemoglobin. They can occur
the sickle cell locus, where probably the HbS allele was on both the a- and b-globin chains. Clinical signifi-
already present at a low frequency, and the malarial cance relates to the degree of hemoglobin reduction,
environment benefited the relatively better adapted and ranges from mildly affected to a fatal condition
heterozygote due to its resistance to the disease. called hydrops fetalis. As in the case of hemoglobinopa-
It would be expected that this process was not strictly thies discussed above, heterozygotes for thalassemia
linear in the sense that selection for the heterozygote offer protection against malaria, and once again due
led to a lasting balanced polymorphism, but rather that to balancing selection, thalassemia markers are main-
as local populations adapted and increased in number, tained, but not necessarily balanced, polymorphisms.
they also expanded in area by clearing more land and Elevated frequencies for these markers were initially
opening up broader opportunity for malarial disease, found in Mediterranean populations, particularly in
and another cycle of selection for the heterozygote. The Greece, Italy, and nearby islands where malaria is
dynamics between genetics and behavior in the sickle endemic. Later, polymorphic frequencies were recorded
cell case can be considered a hallmark of biocultural in New Guinea and Africa, as well as southeastern Asia,
interaction that is so important in understanding where the co-occurrence with HbE was noted above. A
human population history. population genetics survey of this last region showed
The geographic distribution of the HbS marker, that after comparing gene frequencies for two popula-
beyond Africa and into India and South Asia, has tions, one had adapted via the thalassemia marker while
raised questions concerning the number of origins for the other gained malarial resistance from the HbE vari-
the mutation. While Livingstone (1989) had argued for ant. Hence, population history would account for the
a single origin, others have proposed multiple muta- different adaptive route (Vogel and Motulsky, 1997, p.
tions (Labie et al., 1986). Marks (1995) summarizes 533). Additionally, the analysis went on to reveal that
evidence showing that the sickle cell allele is found in since the homozygote HbE/HbE was less deleterious
five haplotypes corresponding to four African areas than the homozygote thalassemia genotype, thalassemia
and one Indian source, that could be interpreted as was being replaced by HbE as the more effective and
independent origins or possibly also a single mutation less costly balancing selection process.
that underwent successive later mutational and cross- Thalassemia was also found to co-occur geogra-
ing-over events. A more complete resolution of this phically with an enzyme deficiency of G6PD, and it
matter may help to answer the question as to whether was presumed this was due to their both offering gen-
or not the HbS marker had a single African origin and etic resistance to malaria. The biochemical explanation
subsequently spread by gene flow beyond the continent for why G6PD deficiency was protective was proved by
232 Robert J. Meier
Friedman and Trager (1981) who showed that the mal- parentage questions and paternity exclusion, zygosity
arial falciparum parasite did not survive in G6PD- determination in twins, and bone and mummified
deficient cells due to a lack of potassium. The island tissue typing.
of Sardinia provided a test of the malarial selection Race and Sanger (1962) devoted chapters to “Blood
hypothesis for both thalassemia and G6PD deficiency. Groups” and “Problems of Parentage and Identity” and
Frequencies for both markers closely correlated with to “The Blood Groups of Twins.” All of these applica-
altitude which largely determined the malarial para- tions relied on serological testing for red blood cell
sitic load. Correspondingly, the lower the altitude the antigens from most of the common blood groups, and
greater the selection pressure at the G6PD locus. for identity determinations rare antigens or unusual
The remaining example pertaining to the malarial combinations of common antigens were thought to
selection hypothesis involves the Duffy blood group be the most useful in assigning individuals to a race.
system. A laboratory was the venue for testing the sus- On this last point, the examples that were provided
ceptibility of red blood cells of the different Duffy indicated a low level of reliability for race identifica-
phenotypes to infection by the malaria parasite Plasmo- tion. Race and Sanger (1962) did not attempt to cover
dium vivax, a benign form and probable predecessor to forensic evidence in criminal cases, except to mention
the malignant derivative P. falciparum (Mourant, 1983). that at that time only the ABO system was applicable
It was found that phenotypes carrying at least one copy through specialized techniques for examining human
of Fya or Fyb were readily infected whereas the Duffy blood and other fluid stains. Of course, present-day
negative Fy0Fy0 (the null Fy0 allele also has been desig- forensic science has an extensive array of DNA-based
nated as Fy’, Fy, and Fy4) was highly resistant to infec- methods for analyzing evidence derived from criminal
tion. Based on these findings it was theorized that the activities.
Fy0 mutation arose from either of the common alleles, Little coverage of bone and tissue typing appeared
and by chance increased in frequency enough to form a in Race and Sanger (1962), which they saw as
few homozygotes that were then at a selective advan- fraught with technical difficulties, some of which
tage when P. vivax malaria became endemic. Living- were inherent to the inhibition method that was
stone (1984) countered this portion of the theory by being used. These problems were well documented
concluding that the Duffy null allele had reached a in a study by Thieme and Otten (1957), who demon-
sufficiently high enough frequency to prevent vivax strated that bacterial contamination could lead to
malaria from becoming endemic in West Africa. false inhibition results, usually due to the transform-
The theory continues that over time the Fy0 marker ation of A and B antigens into O. Their conclusion
progressively replaced Fya and Fyb, and even reached was that bone ABO typing was highly unreliable
fixation in some African populations, as observed under certain conditions, especially if the bones had
today. The next phase was to theorize that tropical been recovered from damp soils. Later researchers
Africa was free of malaria until P. falciparum appeared made improvements in the preparation and testing
and set off a new direction of selection operating on procedures, and claimed to have achieved reliability
hemoglobin variants, including the sickle cell allele. from typing skeletal materials from an archaeological
It is unlikely that historical details of this theory site in Israel (Micle et al., 1977), and mummified
can ever be subjected to direct testing. However, con- tissue from pre-Columbian sites in Peru (Allison,
sidering the several examples cited above that over- et al., 1978) and Chile (Llop and Rothhammer,
whelming confirm the malarial selection hypothesis, 1988). Beyond the limited application and success
it can be expected that portions of it will hold up to of bone/tissue typing, the fledgling field of
further scrutiny. Indeed, the selection hypothesis was “paleoserology” was replaced by ancient DNA extrac-
favored more recently by Hamblin and Di Rienzo tion and sequencing.
(2000) in their investigation of DNA sequence vari-
ation. In general, the early application of markers to a
testing of crucial population genetic questions, espe- TAKING STOCK AND LOOKING AHEAD
cially those surrounding an understanding of how
and why certain polymorphisms are maintained, must Half a century after Boyd’s bold claims for accomplish-
be viewed as highly successful. ments of genetic analysis it probably is pretentious to
make any similar such statements, but certainly there
were significant contributions between 1950 when
ADDITIONAL AND PRACTICAL APPLICATIONS classic markers prevailed and prior to the dominance
OF CLASSICAL MARKERS of molecular methods that is seen today. This section
will offer an overview of the various applications of
Brief mention will be made here with respect to traditional markers as covered earlier but now dis-
additional applications of markers. These are: cussed in terms of how they might continue to
contribute to our understanding of human genetic sets, there are likely to be many instances of stored
variation. aliquots of human sera, saliva specimens, and hair
samples that were collected during much earlier field-
work projects that potentially could be subjected to
POPULATION RELATIONSHIPS AND HISTORY laboratory analysis, but only after all ethical matters
and human subjects concerns are satisfactorily
The first point to make under this topic is that the resolved.
concept of biological race possessed little practical sci- In sum, classical markers served their purpose
entific reality or application among anthropologists/ well in describing human variation and in proposing
human biologists investigating population affinities. plausible affinities between populations until such
To be sure, there is a research need to define units of matters came under the finer-grained scrutiny of
study, but this requirement could not be met through DNA markers. It seems fair to say that although
race classification. In its place, population and variants they are no longer at the forefront of population
such as deme or ancestral group or nonbiological lin- study, classical markers will continue to contribute
guistic and ethnic designations, have been used. to these endeavors as evidenced in the examples cited
A broad-based effort that employed language as its unit above.
of study identifier was the Human Genome Diversity
Project (HGDP). Growing out of the Human Genome
Project in 1991, the HGDP had as its basic aim to map MARKERS AND DISEASE ASSOCIATIONS
human DNA sequence diversity in order to deduce
genetic history of our species. The HGDP became It also seems appropriate to conclude that certain clas-
highly controversial due to ethical issues surrounding sical markers have been increasing over the years in
personal, civil, and legal rights of indigenous peoples their contribution to the study of selection and disease
from whom DNA would be obtained. Since its data set associations. For instance, the HLA system, with its
consists of DNA markers it is beyond the purview of numerous haplotype combinations, is highly note-
this discussion, and the reader is directed to M’charek worthy in this regard. Jackson’s (2000) informative
(2005) for a comprehensive review of the science discussion is replete with relatively recent examples
behind the HGDP. Another global effort to study of interaction between HLA haplotypes and several
human genetic diversity through DNA markers is the infectious diseases, notably HIV/AIDS. Along this HIV
Genographic Project. Under the direction of research- research front, a very recent study has reported a con-
ers from the National Geographic Society and IBM, the nection between HIV susceptibility and Duffy antigen
Genographic Project seeks to trace the deep migra- status. The presence of DARC (duffy antigen receptor
tional history of our species. Up-to-date accounts of for chemokines) appears to increase the susceptibility
the Project can be found at the National Geographic to infection by HIV. But following infection, the DARC-
and IBM websites. negative phenotype leads to a slowing down of the
A recent study (Relethford, 2004) does exemplify a progression of the disease (He et al., 2008).
successful application of classical markers, along with For another marker, a major breakthrough
microsatellite DNA markers and craniometrics, in a was reported by Allen et al. (1997) in that not only did
worldwide analysis of genetic variation in human thalassemia provide malaria resistance in Papua
populations. Relethford obtained frequencies of New Guinea children it also protected against other
blood cell polymorphisms (blood groups, serum pro- infectious diseases, and importantly this finding may
teins and enzymes) from Roychoudhury and Nei apply to other malarial resistant genes, such as HbS,
(1988), much as he had done in a previous study as well. Finally, two very recent studies can be cited
(Relethford and Harpending, 1995). A major point to to show how active this field remains. One found
bring out here is that earlier databases of classical that a haptoglobin phenotype was at much higher
markers obviously can continue to serve contempor- risk for cardiovascular disease in individuals with
ary research purposes. For the most part Birdsell diabetes mellitus (Levy et al., 2002), while the other
(1993), in his study of microevolution on Australia, demonstrated a complex interaction between one of
also followed this path in utilizing marker frequencies the transferrin markers and an allele at another iron
that he had obtained from his fieldwork of nearly a metabolism locus as these posed a prominent risk
half-century earlier. These examples of data mining factor for developing Alzheimer’s disease (Robson
show that while DNA markers certainly rule the day, et al., 2004).
there still can be a place for already available classical It probably is not surprising that these ongoing
marker frequencies to be used in the investigating examples of classical marker associations with various
human population variation and genetic history. At diseases are still being discovered, and of course, just
an even more basic level than marker frequency data as in the earliest of such disease associations
234 Robert J. Meier
discovered decades ago, they are subject to further Boyd, W. C. (1963a). Genetics and the human race. Science,
confirmation. There is every reason to predict that this 140, 1057–1064.
area of research will continue to be a fruitful endeavor Boyd, W. C. (1963b). Four achievements of the genetical
to pursue. method in physical anthropology. American Anthropolo-
gist, 65, 243–252.
Brace, C. L. (2005). “Race” Is A Four-Letter Word. Oxford:
Oxford University Press.
DISCUSSION POINTS Buchi, E. C. (1968). Somatic groups composing the modern
populations of India. In Proceedings of Eighth Inter-
1. Which classical markers continue to be most useful national Congress of Anthropological and Ethnological
in studying human variation and/or disease Sciences. Tokyo: Science Council of Japan, pp. 154–162
associations? Buettner-Janusch, J. (1966). Origins of Man. Physical Anthro-
2. Discuss the pros and cons of Boyd’s classification pology. New York: John Wiley and Sons.
of human races based on blood groups. Cavalli-Sforza, L. L. and Bodmer, W. F. (1999). The Genetics
3. What are the ways in which variation can be main- of Human Populations. Mineola, NY: Dover Publications.
tained at a polymorphic locus? Cavalli-Sforza, L. L., Menozzi, P. and Piazza, A. (1994).
4. On what theoretical grounds can different meas- The History and Geography of Human Genes. Princeton:
ures of population distance (including genetic, Princeton University Press.
Chakravarti, A. and Chakraborty, R. (1978). Elevated fre-
anthropometric, odontometric, dermatoglyphic,
quency of Tay–Sachs disease among Ashkenazic Jews
linguistic, geographic) be expected to correspond
unlikely by genetic drift alone. American Journal of
to or, conversely, to not agree with one another?
Human Genetics, 30, 256–261.
5. Discuss the evidence for and against the malarial Chown, B. and Lewis, M. (1953). The ABO, MNSs, P, Rh,
hypothesis regarding the frequency distributions of Lutheran, Kell, Lewis, Duffy and Kidd blood groups and
hemoglobin variants, transferrins, G6PD, and the secretor status of the Blackfoot Indians of Alberta,
Duffy markers. Include in this discussion the role Canada. American Journal of Physical Anthropology,
of cultural activities related to subsistence patterns. 11, 369–383.
6. What are the underlying reasons that classical mark- Crawford, M. H. (1973). The use of genetic markers of
ers can be expected to be associated with diseases? the blood in the study of the evolution of human pop-
ulations. In Methods and Theories of Anthropological
Genetics, M. H. Crawford and P. L. Workman (eds).
Albuquerque, NM: University of New Mexico Press,
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14 DNA Markers of Human Variation
Michael E. Steiper
INTRODUCTION Although the questions addressed by different

marker types are similar, it is critical to understand
Historically, questions relating to human genetics the relationship between the classical and DNA
and variation have been addressed by the study of markers. Perhaps the most important feature of clas-
“classical” genetic markers (see Chapter 13 of this sical markers is that their allelic variation is due to
volume). Classical genetic markers are polymorphic amino acid level differences. Therefore, in classical
proteins, which run the gamut from blood group anti- marker studies, the genetic variation ascertained is
gens such as the ABO system to enzymes including based solely on DNA regions involved in transcription
G6PD. Each of these classical marker loci has charac- and/or translation. Genetically, these differences
teristics that are useful for addressing questions about between classical marker alleles are caused either by
human genetic variation. These characteristics usually variation in DNA that encodes that gene0 s amino acids
include an appreciable level of polymorphism or variation in its sequence that affects it expression.
(variation) and a methodological ability to consistently This has important consequences for understanding
detect that polymorphism using techniques such as human variation through their lens because the
gel electrophoresis. Often, these variations make clear number of DNA sites that contributes to variation at
links between particular alleles and genetic diseases this level represents only a small portion of the genome
(e.g., the HbS allele of the b-globin gene with sickle cell (<5% (International Human Genome Sequencing Con-
anemia (Pauling et al., 1949), while at other times, sortium, 2001, 2004). Also, because they encode poly-
these relationships are statistical (e.g., particular ABO peptides, classical loci are likely to be under greater
blood type alleles and susceptibilities to diseases surveillance by natural selection than portions of the
[see Chapter 13 of this volume]). The use of classical genome that do not encode for or regulate the expres-
markers for understanding human genetic variation sion of amino acids.
is reviewed in Chapter 13 of this volume. DNA markers, on the other hand, directly address
In the current chapter, I review the application of the physical basis of heredity. As such, DNA markers
more modern “DNA markers” to studies of human can derive from anywhere within the entire nuclear
variation. A host of methodological advances coalesced genome or the mitochondrial DNA, whether the region
in the 1980s that enabled scientists to investigate is coding, regulatory, or noncoding. This is one of the
human variation directly at the level of the genetic key differences between classical markers and DNA
material, hence the name “DNA markers.” Because markers. One of the greatest strengths of the direct
there are several advantages to assaying human genetic study of DNA variation is that most of the genome is
diversity directly at the DNA level, a transition to use of noncoding, and thus presumably not under natural
these markers followed. Importantly, throughout the selection. Consequently, DNA markers occurring in
transition from classical to DNA markers, many of the these regions are considered to be “neutral” in their
key evolutionary questions of human genetics and vari- effects. Neutral DNA markers are extremely useful for
ation have remained constant. These studies address assessing the demographic history of humans, since
the processes that have shaped human genetic diver- these regions are expected to reflect mainly population
sity; the origins, maintenance, and levels of human level effects, such as drift, expansions, admixture and
genetic diversity; the relationship between genetic migration.
diversity, diseases, and disease resistance; the effect The ABO blood group system (reviewed in Chap-
of natural selection on the human genome; the role of ter 13 of this volume) provides a useful example of the
genetics in human biocultural evolution; and the relationships between classical and DNA markers
tracing of human migrations around the globe. (Figure 14.1). The three main alleles of this system
238
DNA Markers of Human Variation 239
Chromosome 9
Microsatellite Exon 1 Exons 2-7
Transcription
RBC
and Protein Antibodies
antigen
N repeats 261 297 526 657 703 796 803 930 Translation
A
A(A1) 1 G A C C G C G G 355 AA Anti-B
Arg Gly Leu Gly
B
B 4 G G G T A A C A 355 AA Anti-A
Gly Ser Met Ala
Anti-A
O(O1) 4 Deletion A C C G C G G 39 AA
Anti-B
– – – – – – –
ALLELES DNA MARKERS CLASSICAL MARKERS

14.1. Schematic diagram of the relationship between DNA markers and classical markers in the ABO
blood group system. At left are the three main alleles: A(A1), B, and O(O1) (there are many other
subtypes of the alleles). The DNA markers associated with the different alleles follow to the right
(adapted from Hosoi, 2008). There is a minisatellite DNA marker in the upstream region of the ABO
gene (Irshaid et al., 1999). There are alleles with one repeat unit and others with four repeat units.
There are a number of single nucleotide polymorphism (SNP) markers in the sixth and seventh exon of
the different alleles. The numbers indicate the base pair location within the coding region, the base
pairs are below the numbers, as well as the amino acids for nonsynonymous changes. The SNPs that
change the amino acid (nonsynonymous) are shown in bold (e.g., 703). A single base pair deletion is
present at position 261 on the O allele, which results in a frameshift that eventually leads to a
premature stop codon. There are also synonymous SNPs in the different alleles (e.g., 930). When
these alleles are transcribed and translated from DNA to amino acids, they form part of the basis for
the ABO erythrocyte antigens (at right of large arrows). Note that individuals who have the genotype
AA and AO are both phenotypically A with respect to their classical markers. The use of DNA markers,
on the other hand, could type the base pair at position 261 or the number of minisatellite repeats and
distinguish between these two genotypes.
are A, B, and O. The gene underlying this system, the differences are the “silent” (or synonymous) DNA
ABO gene, is 18 kilobases long, comprised of 7 exons, sequence differences between the A, B, and O alleles.
and located on human chromosome 9 (q34) (Cook These synonymous DNA differences, as well as changes
et al., 1978); Yamamoto et al., 1995). The A and B within the introns, and the upstream and downstream
alleles are codominant and O is recessive. The A and regions, are not usually reflected in the amino acid
B antigens differ at four amino acids caused by non- chain and, therefore, are “invisible” to classical
synonymous differences in the DNA sequence between approaches. They are also likely to be invisible to nat-
the A and B alleles (Yamamoto et al., 1990). The O ural selection.
allele, which does not produce a functional antigen However, the ascertainment of the complete set
(more precisely, the H antigen is produced), contains of differences in the DNA sequence is instrumental
a single base deletion. This deletion, a nonsense muta- for obtaining a more precise and accurate picture of
tion that results in a frameshift (Yamamoto et al., the population genetics of the ABO system. This infor-
1990), causes a premature stop codon and a truncated mation indicates the origin of the alleles, their evolu-
amino acid chain. tionary history, and their maintenance by drift and/or
The classical methodological approaches are natural selection. For example, DNA marker analysis of
able to distinguish these alleles based on different the ABO gene suggests that the O allele has arisen three
amino acid chains in the case of A and B, or their independent times in human evolution, suggesting it is
nonproduction, in the case of O. However, studies of a selectively advantageous allele (Calafell et al., 2008).
the DNA sequence encoding the A, B, and O alleles have In this chapter, I review the methodological
directly examined the nucleotides responsible for the advances that have permitted the use of DNA markers
amino acid differences. Perhaps more important than in studies of human diversity, including the properties
the DNA changes that result in amino acid chain of different marker types and the different genomic
240 Michael E. Steiper
regions assayed by DNA markers. I will subsequently but only a target region. To achieve amplification of a
review the application of DNA markers to studies of specific genomic target region, PCR goes through three
human diversity, modern human origins, human main steps, proceeding in the following order: denatur-
migration and expansion, natural selection, and the ation, annealing, and extension (Figure 14.2). During
apportionment of human diversity. step one, the denaturation step, the DNA sample (e.g.,
from a human) is heated to unwind the double-
stranded DNA helix. The temperature is about 95 C.
Methodological advances
This unwinding (or melting) into a single-stranded
The most important technical advance facilitating the state is required for the subsequent two steps.
transition from classical markers to DNA markers was The second step, called annealing, allows a particu-
the polymerase chain reaction (PCR) (Mullis and lar region of the genome to be targeted through the use
Faloona, 1987). The PCR technique allows for the amp- of small DNA molecules called “primers,” “oligonucleo-
lification of a target region of a genome so that it can tides,” or “oligos.” These primers are small (~20 base
be studied in great detail. These targets can be from pair), single-stranded DNA molecules that bracket the
any region of any genome (nuclear or mitochondrial) target region (in the figure, smaller primers are used
or even any sample that contains DNA, such as an for readability). Usually there are two unique primers
environmental sample (e.g., Sebastianelli et al., 2008). and they are designed and synthesized for use in a
The PCR technique produces a very large quantity of particular PCR. Often, the known DNA sequence of
DNA from even very small amounts of starting DNA the region of interest is examined to find appropriate
from the target DNA region. This PCR-amplified locations for the primers. This has been great facili-
DNA can be examined by a host of other methods, tated by the many DNA sequences publicly available
which indicate its sequence or length. The PCR tech- (see GenBank at http://www.ncbi.nlm.nih.gov [Benson
nique is critical to most subsequent applications in et al., 2004]). One primer has the complementary
the ascertainment of population genetic variation. sequence to a region of the genome located at the most
Indeed, the use of the PCR to examine genetic poly- upstream (or 50 ) margin of the target region, and the
morphisms from a wide sample of humans is the other primer has the complementary sequence of the
essence of modern human population genetics with most downstream (or 30 ) margin of the target region.
DNA markers. Importantly, PCR is relatively inexpen- The step is called annealing because the reaction is
sive, rapid, and standardized. cooled to a temperature (~55 C) that allows these two
Obtaining DNA for use in PCR requires access to primers to anneal or bind to the denatured DNA. These
any human cells that carry genomic DNA. This is very primers are able to bind to specific regions of the
different from classical markers, which are proteins, genome in the target sequence because they are gener-
and can only be purified from samples in which the ated from a known DNA sequence (and thus can be
proteins are produced. For example, to study the clas- designed to match the sequence of the target region
sical protein marker locus albumin, the plasma portion exactly, ensuring that they will anneal to the target).
of blood must be used to purify the albumin proteins. Also, their length (approximately 20 base pairs) usually
However, the DNA that underlies the production of the precludes spurious matches elsewhere in the genome.
albumin proteins is located on human chromosome 4 Software programs for primer design are available
and present in all nucleated human cells. Therefore, (e.g., Untergasser et al., 2007).
the direct study of an albumin gene can be conducted The third step of PCR is called extension or elonga-
from DNA purified from any human cell sample: blood, tion. In this step, the DNA polymerase enzyme elong-
cheek swabs, placenta, hair bulbs, or other tissues. ates DNA molecules from the 30 -most-base of both
Combined with very minimal requirements for the primers using the genome in the sample as a template.
amount of genomic DNA to be used with the PCR, The reaction is heated to 72 C which causes the poly-
genetic analysis of DNA markers is simpler than analy- merase to elongate a new DNA molecule along the
sis of classical markers. Obtaining tissue or DNA template strand. This is done in the presence of add-
samples from a sufficient sample of humans for popu- itional free DNA bases (deoxy A, C, T, and Gs) that are
lation genetics study can be difficult. Global sampling incorporated by the polymerase during the elongation.
has been greatly facilitated by the collection and DNA polymerase used in PCRs comes from a heat-
availability of cell lines from diverse humans (Cann adapted bacterium called Thermus aquaticus (or Taq)
et al., 2002). that lives in hot springs. This enzyme is used because it
Polymerase chain reaction is a technique that is an can withstand heating to denaturation temperatures.
in vitro appropriation of organism0 s mechanisms for In these initial steps, when the sample is the main
replicating their own genomes using DNA polymerase template DNA, the elongated copies extend from one
enzymes. However, as noted above, during most PCRs, primer along the DNA molecule beyond the second
it is not an entire genome that is being replicated, primer. These three steps comprise a single PCR cycle.
Starting materials:
Genomic DNA, primers,
DNA polymerase, bases.
1 Cycle
1 Cycle
~20–40 Cycles
Denaturation at ~95°C Annealing at ~55°C Extension at ~72°C

14.2. A schematic of the polymerase chain reaction (PCR), which is described in the text. Polymerases
are gray dots. Fine arrows at the end of DNA strands denote that the strand continues in this
direction. The 5’ and 3’ denote the directionality of the different DNA strands; the format of the first
cycle is followed throughout. The DNA strands given in black are present in the initial stage of the
reaction and are the genomic DNA and primers. The DNA strands given in medium gray are those that
have a primer anchoring one side of the strand, but extend beyond the target area. The DNA strands
given in the lightest gray are only the target region, between the two primer annealing locations. It is
these light gray DNA copies that are created in large amounts during PCR. These are highlighted by
faint gray in the bottom right box.
At the end of this PCR cycle, there are now additional electric charge to separate DNA by length across a
copies of the target region in addition to the genomic matrix, such as agarose gel. It is at this stage that the
template. This cycle is then repeated, as it is a “chain level of genetic variation can be assessed by the exam-
reaction.” In the second cycle, the newly polymerized ination of many different properties of the amplified
DNA molecules are also denatured. Similarly, during DNA target. The two main properties of these ampli-
annealing, the primers can bond to either the original fied target regions are their size (or length) and their
template or the newly generated templates. Extension DNA sequence.
will also occur at the genomic DNA and the newly
generated templates. During these subsequent cycles,
Types of DNA markers
when a primer anneals to a newly generated template,
molecules will be created that only correspond to the Three of the most important types of DNA markers
target region between the primers. With each cycle, for studies of human variation will be addressed at
additional copies of the target region are made and length: microsatellites, single nucleotide polymorph-
these copies themselves can serve as templates in sub- isms, and restriction fragment length polymorphisms.
sequent cycles. This leads to an exponential increase in Less frequently used DNA markers, such as Alu and
the number of target DNA molecules. Most PCR proto- LINE elements (Xing et al., 2007) and copy number
cols utilize between 20 and 45 cycles to generate large variants (Jakobsson et al., 2008), are important for
amounts of the target region. Indeed, PCR can be initi- understanding human diversity, but will not be directly
ated from very low numbers of genomic DNA copies, addressed here.
even single genomes, making it useful for applications Though they are not used extensively as markers at
such as forensics and ancient DNA where samples may present, restriction fragment length polymorphisms
contain only small amounts of template DNA. (RFLPs) (Botstein et al., 1980) are useful to understand
At the end of a PCR, a large amount of a target as a methodology for both historical and practical pur-
region of the genome is generated. Often, a sample of poses. This type of marker exposes DNA to enzymes
the target DNA generated in a PCR is then visualized that cut at short and specific DNA motifs of approxi-
with gel electrophoresis. Electrophoresis uses an mately 4–6 base pairs in length. These enzymes are
called restriction enzymes or restriction endonu- deletions are called SNPs, as well. A database of known
cleases. They are purified from different bacteria human SNPs, called dbSNP, is available (http://www.
species, where they cleave and destroy exogenous ncbi.nlm.nih.gov/projects/SNP/ [Sherry et al., 2001]).
DNA. Each bacterium has its own set of restriction There are a host of methods to catalog and type
enzymes that recognize particular DNA motifs, or rec- known SNPs. One of the most important methods is
ognition sites. the gene chip (Wang et al., 1998), though there are a
A common restriction enzyme is EcoRI, which is host of other methods for finding and type SNPs, such
purified from Escherichia coli. This enzyme will cut as single-strand conformation polymorphism (SSCP)
DNA at the palindromic motif 50 -GAATTC-30 . (Methyl- and allele-specific PCR (Kwok and Chen, 2003). The
ation protects an E. coli0 s own DNA from cleavage at advantage of typing known SNP markers by these
the recognition site.) The double-stranded DNA is methods is that many alleles can be assessed at once
cleaved between the G and the A on each strand, (yielding high throughput), although only known poly-
resulting in a short, single-stranded overhang on each morphisms can be detected. For this reason, such
strand, sometimes referred to as a “sticky end.” Other methods can miss rare polymorphisms, which are very
enzymes cleave in a position that leads to “blunt ends,” important to catalog for population genetics studies.
without an overhang (e.g., EcoRV cutting between the One important method that detects all SNPs
T and A in the motif 50 -GATATC-30 ). Today, hundreds is direct DNA sequencing of genetic regions (see
of different restriction enzymes that can recognize Chapter 4 of this volume). Comparison of DNA
many different DNA sequence motifs and cleave them sequences between samples of alleles will reveal all
in different ways are available to researchers. SNPs, as well as all other types of genetic variation in
A database of enzymes, called REBASE, is available a population. Complete sequencing of DNA within
(see http://rebase.neb.com/rebase/rebase.html; Roberts population samples is sometimes referred to as “rese-
et al., 2005). quencing” (e.g., Voight et al., 2006; Kelley et al., 2009).
As a simple RFLP example, one can use PCR to Resequencing has the advantage of finding novel poly-
amplify a target region 600 base pairs in length. At morphisms, but it has the disadvantage of covering
the 200th base pair of this region, the sequence motif regions of DNA that are identical, which can be costly.
50 -GATATC-30 is present. Nowhere else in this 600 base- Advances in automated DNA sequencing methods will
pair region is this motif present. When this amplified enhance the ability to easily sequence stretches of DNA
DNA sample is exposed to EcoRV, it will be digested or for population studies (Bentley, 2006; Stratton, 2008).
restricted into two pieces, one that is approximately Microsatellite DNA regions are a class of repetitive
200 base pairs and another that is 400 base pairs. DNA elements composed of tandemly repeated motifs
When separated by size using gel electrophoresis, two of up to six base pairs in length. These regions are also
DNA fragments will be present, one 200 and the other known as short tandem repeat loci (STRs) or simple
400 base pairs in length. When this sequence motif is sequence repeats (SSRs). The STRs have motifs such
not present within the amplified fragment, only one as “GA” or “TAC” repeated a number of times, usually
DNA size will be present, 600 base pairs, even if it is up to a few hundred base pairs in length. The alleles are
exposed to the EcoRV restriction enzyme. If this motif designated by their repeat length, e.g., (GA)n.
is variable within a population (e.g., 50 -GATATC-30 in Microsatellites have a number of properties that
one allele and 50 -GATACC-30 in another allele), it can make them very useful genetic markers for evolution-
be assessed as a polymorphic genetic marker. These ary studies (Schlötterer, 2000). Firstly, these regions
markers are used by assessing the variation in the are interspersed throughout the human nuclear
fragment lengths generated by different restriction genome. Because evolution can be a stochastic (i.e.
enzymes, hence, the term RFLPs. Because a relatively random and nondeterministic) process, this allows
large amount of DNA is required to visualize RFLPs, markers to derive from many different independently
the DNA examined is often PCR amplified DNA or evolving genomic regions. Also, markers can be chosen
purified mitochondrial DNA. from particular regions of the genome (e.g., neutral
Single nucleotide polymorphisms (SNPs) are single noncoding regions, low recombination regions, par-
base-pair differences between two alleles of a particu- ticular chromosomes, or regions near a particular
lar DNA region. For example, two alleles might differ gene). Secondly, they are codominant and relatively
at the 112th base pair in a gene sequence, with one simple to type, i.e., to ascertain the different alleles
having a “G” base and the other having an “A” base. present at a specific locus. In brief, PCR primers
Single nucleotide polymorphisms are found through- are designed for regions flanking the STR region, and
out the nuclear and mitochondrial genomes, and act as the region is amplified. Subsequent to PCR, a sensitive
codominant markers. While the level of polymorphism electrophoresis is used to decipher size differences of
at these positions varies, they are usually less variable the alleles, distinguishing between alleles that even
than satellite markers. Sometimes small insertions and differ by a single repeat, e.g., (CA)22 and (CA)23 alleles.
This resolution is achieved through the use of fluores- (mtDNA). Therefore, in most tissues, there are many
cently tagged primers and capillary electrophoresis- more mitochondrial genomes present than nuclear
based machines. Third, STRs are often highly variable genomes.
due to their having a high mutation rate, about 10 6 to The mtDNA genome has a number of unique prop-
10 2 per generation, due to slippage during DNA repli- erties because of its evolutionary history (reviewed
cation (Schlötterer, 2000). This means there are usu- by Pakendorf and Stoneking, 2005). To begin with,
ally many alleles at a particular microsatellite locus, it is a plasmid, or a circular molecule, of relatively
allowing for discrimination between individuals at very small size, only 16 569 base pairs in length. The major-
close levels. Fourth, multiple microsatellite loci can ity of its DNA consists of coding sequences or genes,
often be amplified within the sample PCR, allowing although it uses a slightly different genetic code
these loci to be typed at the same time (referred to as than nuclear DNA. In addition, it does not recombine,
multiplexing). is haploid and maternally inherited, and mutates
Overall, STRs are useful DNA markers for more rapidly than nuclear DNA. The first mito-
population genetics studies, relatedness studies (e.g., chondrial genome sequence was published in 1981
paternity or sibship analyses), molecular ecology appli- (Anderson et al., 1981) and has been further refined
cations, forensics, and genetic mapping. Some (Andrews et al., 1999).
microsatellite markers are named for genes that Relative to the mtDNA genome, the nuclear
they are associated with (e.g., FGA is a marker in the genome is very different. A human nuclear genome
fibrinogen a-chain gene), while others are named draft sequence was first published in 2001 (Inter-
for their location in the genome (e.g., D3S1358 is loca- national Human Genome Sequencing Consortium,
ted on human chromosome 3). A database of known 2001; Venter et al., 2001) and then finished several
human microsatellites, called STRbase, is also avail- years later (International Human Genome Sequencing
able for researchers (http://www.cstl.nist.gov/biotech/ Consortium, 2004). Based on this work, we now know
strbase/ [Ruitberg et al., 2001]). A related kind of that a complete haploid human DNA sequence is about
DNA marker is the minisatellite, which involves 3.08 billion base pairs long. Somewhat surprisingly,
repeat motifs longer than microsatellites, up to about researchers discovered that less than 5% of the genome
100 base pairs. encodes genes and that there are between 20 000 and
In a sense, RFLP loci are similar to SNPs because 40 000 protein-coding genes per genome (International
they usually reflect single base-pair changes, but they Human Genome Sequencing Consortium, 2001, 2004).
are assessed in a manner similar to STRs, based Many important features of the genome, such as
on their length. The RFLP method is useful because the number of coding loci, the GC-content, and recom-
it is relatively rapid, inexpensive and simple, and bination rates, show considerable heterogeneity.
the markers behave in a codominant manner. Interestingly, about 50% of our nuclear genome com-
A shortcoming is that only very few base-pair differ- prised of transposable elements (International
ences (SNPs) are assessed in a sequence by restriction Human Genome Sequencing Consortium, 2001). More
enzymes, although use of multiple enzymes can result information about the Human Genome Project, includ-
in a large proportion of total nucleotides being ing access to “Landmark Papers,” is found at the fol-
assayed. Also, absence of digestion can be caused by lowing website: http://www.ornl.gov/sci/techresources/
multiple different mutations, meaning that more Human_Genome/home.shtml.
alleles may be present than can be reliably assessed. Within the nuclear genome, there are 22 autosomal
chromosomes, each with biparental inheritance, and one
set of sex chromosomes (X and Y). Males have an X and
Regions of the human genome
Y chromosome; females have two X chromosomes. The
For the purposes of assaying human genetic diversity Y chromosome is haploid, relatively small with few genes,
using DNA markers, it is imperative to understand and is paternally inherited (i.e., passed from father to
the properties of the different genomic regions that son). It also does not recombine for most of its length
comprise “the human genome.” Most important is (except where required in male meiosis). The nonrecom-
the distinction between the mitochondrial genome bining part of the Y chromosome (sometimes abbrevi-
and the nuclear genome. Both genomes are made from ated as NRY for nonrecombining Y chromosome region)
DNA and reside within most cells. Within each nucle- is often targeted for evolutionary studies. The X chromo-
ated cell, there is one copy of the nuclear genome in the some, on the other hand, is relatively large, has many
cell nucleus. However, within each cell0 s cytoplasm more genes than the Y chromosome, and recombines
there are from a few to many thousands of mitochon- in females (who have two X chromosomes), but not in
dria, which produce energy in the form of adenosine males. The autosomes, X chromosome, Y chromosome,
triphosphate (ATP) for the cell. Each mitochondrion and mtDNA are sometimes referred to as different genetic
possesses many copies of the mitochondrial genome compartments (e.g., Garrigan and Hammer, 2006).
Choosing DNA markers for the study of human (e.g., chr. 22 p ¼ 0.088% [Zhao et al., 2000]; chr.1 p ¼
variation 0.057% [Yu et al., 2001]; 50 autosomal loci p ¼ 0.088%
[Yu et al., 2002a]; 20 autosomal loci p ¼ 0.116%, [Wall
The three types DNA markers discussed above, micro-
et al., 2008]; review of earlier studies p ¼ 0.116 for
satellites, SNPs, and RFLPs, have different distribu-
autosomal loci [Przeworski et al., 2000]). These latter
tions in the genome. Loci that contain small single
estimates were generated from “resequencing” studies
base-pair polymorphisms, SNPs and RFLPs, are dis-
that examined DNA sequences completely, not through
tributed throughout the entire human genome.
the screening of samples for known SNP markers.
Due to the compact and mainly functional nature of
However, use of SNP markers can introduce an ascer-
the mtDNA genome, microsatellites are not found
tainment bias because the populations used to find
there. These repeat loci are instead scattered through-
variable SNPs are likely to show higher variation than
out the nuclear genome, usually outside of coding
SNPs recovered from a resequencing strategy (Wall
regions.
et al., 2008). Although there is variation across the
Markers have other properties that make them
genome, a “rule of thumb” is that two random human
more or less useful for examining different population
alleles have about one difference per 1000 base pairs of
genetics questions. For fine-scale processes that have a
autosomal DNA sequence (Tishkoff and Verrelli, 2003).
recent time frame, such as recent migrations, recent
There are additional patterns in the genome. In the
expansions, and relationships between individuals,
X chromosome, nucleotide diversity is somewhat
markers that harbor a great deal of diversity are used.
lower than the autosomes (e.g., p ¼ 0.047% [Inter-
These markers have higher mutation rates. For exam-
national SNP Map Working Group, 2001]; p ¼ 0.1%
ining broader processes including those operating fur-
[Wall et al., 2008]; p ¼ 0.065% [Przeworski et al.,
ther in the past, more slowly evolving markers are
2000]) while Y chromosome nucleotide diversity is
preferable, since the action of subsequent mutations
lowest of all (e.g., p ¼ 0.0135% [Hammer et al., 2003];
can sometimes overwrite these genetic signals. In gen-
p ¼ 0.0151% [International SNP Map Working Group,
eral, microsatellite loci mutate more rapidly than the
2001]). Mitochondrial DNA, on the other hand, has
base substitutions that lead to SNPs and RFLPs
much higher polymorphism (based on 53 whole
(Schlötterer, 2000). Therefore, in general terms micro-
mtDNA genomes [not including D-Loop] p ¼ 0.28%
satellites are useful for assessing diversity within the
[Ingman et al., 2000]; based on 277 whole mtDNA
nuclear genome and can trace fairly recent and fine-
genomes [protein-coding genes only] p ¼ 0.306%
scale population genetics processes including related-
[Kivisild et al., 2006]) because of its high mutation rate.
ness, demography, and migration. Both SNPs and
These levels of diversity can be closely examined in
RFLPs are useful in this regard, but their slower muta-
a number of ways to help understand human variation.
tion rate may not provide enough variation to resolve
Because DNA markers often reside in regions of the
these questions. Also, in general, the SNP and RFLP
genome that are not subject to selection, they can be
loci are more frequently present within or near coding
very informative about human demography and popu-
regions and, therefore, can help to answer direct ques-
lation history. Indeed, the level of neutral genetic diver-
tions about natural selection0 s role in shaping diversity
sity in a population or species is a reflection of
at loci. DNA markers from the mtDNA, the Y, and the
demographic parameters. A simple formula, called
X chromosomes can also be used to trace sex-specific
the population mutation parameter or population
processes, such as migration of females, described fur-
mutation rate, expresses this simply as y ¼ 4Nem. This
ther below.
formula means that the overall level of genetic diversity
at a locus (y) is equal to the effective size of a popula-
tion (Ne) multiplied by the locus0 neutral mutation rate
HUMAN GENETIC DIVERSITY per generation (m) times 4 (4 for nuclear genes; 2 for
mtDNA and Y chromosomes; 3 for X chromosomes;
Human genetic diversity can be assessed using this reflects how many effective copies are present in
these different markers. For example, an analysis of individuals). The formula holds for a population that is
1.42 million nuclear SNP markers in 24 diverse at “equilibrium,” when the role of mutation (m) in
humans estimated nucleotide diversity (p) to be adding new alleles to a gene pool has stabilized with
0.075% (International SNP Map Working Group, effective population size (Ne), which determines the
2001). Nucleotide diversity is the average number of loss of alleles due to genetic drift. For example, a study
pairwise differences in a sample of alleles (Nei, 1987). of the same locus in two populations at equilibrium
Studies that have examined nuclear DNA sequence with equal mutation rates (m), the population with
data from larger samples of humans from across the more diversity (a larger y) would be inferred to have a
globe usually find somewhat higher levels of poly- larger effective population size (Ne) than the popula-
morphism, despite examining fewer overall SNPs tion with the smaller y (all other things being equal).
One useful estimator of y is nucleotide diversity (p), a number of noteworthy features. Firstly, the tree was
which was summarized above for autosomes, sex structured such that the deepest branch led to one
chromosomes, and mtDNA. Using the equilibrium for- set of individuals of African ancestry and a second set
mula and estimators for the mutation rate, levels of of individuals that were from Africa and elsewhere in
human nucleotide diversity are consistent with a the world. Parsimony suggested that the root of this
human effective population size (Ne) on the order of tree, and thus the origin of modern humans, would
10 000 individuals across loci (Garrigan and Hammer, have to have been in Africa. Secondly, Cann et al.
2006). Clearly, this is far fewer than our current census (1987) used a mutation rate scaled to time to estimate
size (N) of 6 billion individuals. Although the effective a date for the deepest node in the study (referred to
population size is usually less than the census size as the time to the most recent common ancestor,
(Frankham, 1995) due to factors such as age stratifica- or TMRCA). This rate yielded a TMRCA estimate of
tion in the census population, an effective population- 140–290 kya (thousands of years ago). These two
size estimate of 10 000 is substantially different from aspects of the tree were interpreted to be consistent
our census size. This strongly suggests that humans are with a “Recent African Origin” model for anatomically
currently not in an equilibrium state and perhaps have modern Homo sapiens (AMHS) (this is also known as
an evolutionary history reflective of population fluctu- the “Rapid Replacement,” “Mitochondrial Eve,” or
ations and sizes that were different than at present. “Out of Africa” model).
In addition to nucleotide diversity, DNA markers There are a number of models for modern human
preserve a great deal of additional information such origins. All models attempt to explain how AMHS
as the pattern and depth of branching relationship became distributed throughout the globe within the
between alleles, patterns of linkage disequilibrium last 100 kya. Prior to AMHS, there were other hominins
(nonrandom association of alleles), and recombin- present in the Old World. These included H. erectus,
ation. More careful scrutiny of particular sets of these H. neanderthalensis (Neanderthals), and H. heidelber-
markers can therefore be informative about the past gensis. The earliest of these hominins (H. erectus and
processes that have resulted in our current levels, pat- related species) are found throughout the Old World
terns, and distribution of genetic diversity. Studies of (Africa, Eurasia, and Southeast Asia) and date to about
these markers in humans have led to considerable 1.8 million years ago (Feibel et al., 1989; Gabunia et al.,
insight in modern human origins, patterns of human 2000; Swisher et al., 1994).
migration, instances of natural selection, and other Models for modern human origins attempt to
topics, which will now be reviewed. explain how all of these species are related to one
another in time and space. In general, the Recent
African Origin model holds that AMHS originated
DNA markers and the origin of modern humans
approximately 100–200 kya within Africa (Stringer
Our current patterns, levels, and distribution of genetic and Andrews, 1988). These AMHS individuals spread
diversity are the product of evolutionary processes, from Africa and rapidly replaced all other archaic
including the ongoing effects of mutation, drift, gene populations of hominins without interbreeding.
flow, and selection. Because of this, anthropologists The main competing model is the “Multiregional Con-
have examined genetic diversity to offer insights into tinuity” model (Wolpoff et al., 1984). This model gen-
the evolutionary history of our species. One critical erally argues for a degree of genetic continuity and
issue is modern human origins, which specifically con- ancestor-descendant relationships between the archaic
cerns questions about when, where, and how our and modern forms of humans. The continuity was
species originated. Because much of our genome is maintained in some manner via gene flow, perhaps
noncoding, it is expected to primarily reflect our demo- since the earliest members of Homo, such as H. erectus
graphic history, instead of the effects of natural selec- left Africa ~1.8 million years ago, up to our present
tion. DNA markers from neutral parts of the genome gene pool.
can therefore be especially useful to understanding Importantly, these two models make predictions
human origins. for human genetic variation that can be tested with
One of the pioneering studies that used DNA data from DNA markers. The Recent African Origin
markers to address human evolution was that of Cann model predicts that the TMRCA for most loci should
et al. (1987), which examined RFLPs from the purified be distributed recently (Takahata, 1993; Ruvolo, 1996;
mitochondria from 147 humans. This is the classic Garrigan and Hammer, 2006), with the TMRCA being
“Mitochondrial Eve” paper. In this study, Cann et al. ~200 kya for mtDNA and Y chromosomes, and ~600
(1987) generated a tree based on the mtDNA RFLPs kya for X-linked DNA and nuclear DNA. Differences in
from their sample of humans. An example of this type age predictions among markers are due to the different
of tree, a coalescent tree, is shown in Figure 14.3 and is effective population sizes of these different genomic
discussed further below. This human mtDNA tree had regions based on their mode of inheritance. On the
T-12
T-11
MRCA
T-10 TMRCA
(from T0)
T-9
T-8
T-7
T-6
T-5
T-4
T-3
T-2
T-1
The present
T-0
generation
14.3. A simplified coalescent tree of alleles at a haploid locus in a “Wright–Fisher” population, which
has a number of simplifying assumptions, e.g., non-overlapping generations. Redrawn from a simula-
tion at the website www.coalescent.dk. The present simulation is only one random genealogy with 8
individuals for 12 generations. Additional simulations would result in different genealogies. Additional
simulations under different parameters can be conducted at the website listed above. T-0 denotes the
present, and T-N corresponds to past generations. In general, when the only factors affecting muta-
tion and the number of alleles that are transmitted are chance, this is the neutral model. In this case,
the amount of genetic diversity is a result of the population size (drift) and the mutation rate. In this
example, sampling all alleles at T-0 (black lines) and estimating a coalescent tree would recover an
MRCA at the time T-10 (this is the most recent common ancestor [TMRCA]). Gray lines indicate
individuals that do not have descendents that reach the present generation. A larger population size
would likely mean that the TMRCA would be older. This can be investigated further at the simulation
website. Note that at T-10, the TMRCA exists in a single individual, but that individual is part of a
population of 8. This is analogous to the “Mitochondrial Eve”: a single allele in a population of alleles.
Also, note that in past generations, the TMRCA would be different. For example, if all alleles were
sampled at a different time in the past, the TMRCA would be older. The same process works going
forward, for example, one of the alleles at T-0 may be the TMRCA of alleles at a generation in the
future. Also, genetic compartments with different effective population sizes, such as mitochondrial
DNA (mtDNA) and autosomes, are predicted to have different TMRCAs.
other hand, the Multiregional Continuity model pre- 1992). The Recent African Origin model also predicts
dicts that each gene0 s TMRCA could be substantially that most genes would be most diverse within African
older, perhaps over 1.8 million years old. populations than elsewhere, and that trees of alleles
The Recent African Origin and Multiregional Con- will have their deepest node inferred to be placed in
tinuity models also make different predictions for the Africa (Takahata et al., 2001). The Multiregional
human effective population size, which can be esti- Continuity model predicts a lack of patterning in these
mated from genetic data using y ¼ 4Nem. The Recent features.
African Origin model predicts a small effective popula- It is also important to note that these predictions
tion size due to AMHS having recent evolved from a are based on very “strong” and simple versions of each
restricted distribution. The Multiregional Continuity model, i.e., these two models do not incorporate much
model predicts a larger effective population size, due complexity. While these “strong” models are useful
to extensive migration across most of the globe among historically and pedagogically, there are more sophisti-
a large, fairly cohesive gene pool, which is likely to cated models of human evolution which contain ele-
require many humans (Rogers and Harpending, ments of both (Stringer, 2002; Relethford, 2001).
Returning to Cann et al. (1987), based on the pre- evidence from mtDNA hypervariable sequences for the
dictions of each model, this study is widely held to oldest expansion in East Africa (105 kya) and the
support the Recent African Origin model. Further- youngest in Europe (42 kya). Ingman et al. (2000)
more, subsequent studies of human mtDNA have con- examined 53 nearly whole genome mtDNA sequences
firmed this interpretation with a TMRCA of roughly from 14 different linguistic groups and detected evi-
200 kya and the root node of the tree parsimoniously dence for an expansion outside of Africa dating to
placed in Africa (e.g., TMRCA ¼ 166–249 kya, 135 38.5 kya.
control region seqs [Vigilant et al., 1991]; TMRCA ¼ These studies provided two interesting insights
222 kya, 5 human COII seqs [Ruvolo et al., 1993]; about modern human origins. Firstly, the estimated
TMRCA ¼ 171.5 kya, 53 whole mtDNA seqs [Ingman population size before the expansion was estimated
et al., 2000]; TMRCA ¼ 160 kya, 277 mtDNA genome to be small (<2000 individuals), which is difficult to
seqs [Kivisild et al., 2006]; TMRCA ¼ 194.3 K, reconcile with a Multiregional Continuity model that
320 mtDNA genome seqs [Gonder et al., 2007]; requires a contiguous population distributed through-
TMRCA ¼ 203 kya, 624 mtDNA genome seqs [Behar out the Old World (Rogers and Harpending, 1992).
et al., 2008], see original studies for confidence inter- Secondly, the timing of the expansion of human popu-
vals). The levels of nucleotide diversity can also be lations substantially postdates the TMRCA for the
compared to assess their fit to the different models. mtDNA trees suggesting that the “strong” Recent
A recent, comprehensive study of mtDNA genomes African Origin model may not strictly hold (Harpend-
found much higher diversity estimates for samples ing et al., 1993). Human dispersals, differentiation, and
from Africa (p ¼ 0.392) versus outside of Africa (p ¼ isolation may have occurred between the mitochon-
0.181) (Gonder et al., 2007), which is consistent with a drial TMRCA but before population expansion, leading
Recent African Origin model. to the proposal of the “Weak Garden of Eden” model
Other interesting inferences can be drawn from (Harpending et al., 1993).
mtDNA data sets. For example, the difference in esti- While these studies all support the Recent African
mates of our effective population size (10 000) and Origin model, there is evidence that natural selection
census size suggests that human population size has may have played a role in shaping human mtDNA
changed dramatically over our history, as a conse- diversity (e.g., Ruiz-Pesini et al., 2004; Kivisild et al.,
quence of expanding or contracting through bottle- 2006; Balloux et al., 2009). Although the patterns cited
necks (i.e., dramatic population size reductions), above are not in dispute, the cause of them may be
during our 200 000-year history. Human mtDNA natural selection rather than demographic processes.
markers have other features that suggest population Because mtDNA does not recombine, the action of
expansion, including an excess of rare sequence vari- selection will affect the entire genome due to genetic
ants and a “star-shaped” phylogeny of alleles “hitchhiking.” This makes the action of positive selec-
(Di Rienzo and Wilson, 1991; Merriwether et al., 1991). tion strong in its potential effects on reducing diversity.
A useful summary of these features is the distribu- Additional work demonstrating the different relative
tion of differences when alleles are compared pairwise roles that selection and demography have played on
(the pairwise mismatch distribution) (Di Rienzo and human mtDNA diversity would be welcome.
Wilson, 1991; Rogers and Harpending, 1992; Harpend- The Y chromosome has also been the target of a
ing et al., 1993, 1998; Sherry et al., 1994). Population number of studies that address modern human origins.
expansions result in a unimodel or “bell-shaped” mis- It has some features that are analogous to those of the
match distribution, while a multimodal (or “ragged”) mtDNA, such as its uniparental inheritance and its lack
distribution is consistent with constant population of recombination over a large part of its length.
size. Furthermore, expansion times and populations In other ways, it is quite different, in particular,
sizes can be estimated for unimodal distributions. because of its paternal inheritance, larger gene-poor
Human mtDNA marker data sets generally show sequence, and slower mutation rate.
evidence for population expansions in different human In one of the first studies of this chromosome,
groups beginning about 100 kya (Rogers and Harpend- Hammer (1995) examined DNA sequences from a 2.6
ing, 1992; Harpending et al., 1993, 1998; Excoffier and kilobase-pair region of the Y chromosome from 16
Schneider, 1999; Ingman et al., 2000). These analyses humans. The TMRCA of these alleles was estimated
also suggest that some populations did not experience to be 188 kya and the effective population size was
expansions, while others experienced bottlenecks, and ~10 000 individuals. These aspects of the analysis were
the timing of expansion differed in different parts of inconsistent with the Multiregional Continuity model,
the world (Di Rienzo and Wilson, 1991; Rogers and and the Y chromosome and mtDNA were shown to be
Harpending, 1992; Harpending et al., 1993, 1998; in agreement with the Recent African Origin model.
Excoffier and Schneider, 1999; Ingman et al., 2000). Subsequent studies of Y chromosome diversity
For example, Excoffier and Schneider (1999) recovered have included the analysis of microsatellite markers
(Hammer et al., 1998; Pritchard et al., 1999). Overall, of unlinked loci from across the genome in order to
this work has confirmed the consistency of the make more precise and accurate interpretations for the
Y chromosome data with the Recent African Origin origins of modern humans, including differentiation
model, including a recent TMRCA, higher diversity between models including the Recent African Origin
within African populations compared to those from model, the Multiregional Continuity model, and others
other parts of the world, and the node of the human (Ruvolo, 1996; Garrigan and Hammer, 2006). This has
Y chromosome tree being parsimoniously placed in been a major impetus for examining numerous DNA
Africa (e.g., Hammer et al., 1998, 2003; Pritchard markers from the recombining nuclear genome for
et al., 1999; Thomson et al., 2000; Underhill et al., addressing modern human origins.
2001). Microsatellite markers (Pritchard et al., 1999) Early studies of DNA markers within the recombin-
and SNP markers (Thomson et al., 2000) on the ing nuclear genome (the 22 autosomes and the
Y chromosome also show evidence for a population X chromosome) provided many additional windows
expansion. onto human evolution. Goldstein et al. (1995) esti-
Because it is nonrecombining, the Y chromosome mated a TMRCA of 156 kya years and a tree rooted in
may be subject to natural selection in the same way Africa for 30 microsatellite markers. Tishkoff et al.
that the mtDNA genome is. Some analyses support a (1996) examined two linked DNA markers within the
role for selection in shaping Y chromosome diversity in CD4 gene in 1600 humans and found a recent African
humans (Jaruzelska et al., 1999). On the other hand, origin for all non-African populations (~100 kya).
the TMRCA of the Y chromosome alleles has been Harding et al. (1997) examined 349 DNA sequences
shown to be consistently about half as old as for from the b-globin locus, and estimated the TMRCA of
mtDNA, which may reflect demographic differences its alleles to be 800 kya and most parsimoniously
between males and females (e.g., differences in placed in Africa, although there was a large amount
mating) (Wilder et al., 2004b). However, overall, with of ancient diversity in Asia. By contrast, Harris and
regard to the origin of modern humans, mtDNA and Hey (1999b) examined DNA sequences from the
Y chromosomes are thought to yield generally similar X-linked PDHA1 gene, and estimated a TMRCA of
scenarios (Underhill and Kivisild, 2007). 1860 kya, as well as extremely different patterns of
Often, because of its matrilineal nonrecombining variation between Africans (high diversity) and non-
inheritance, the most recent common ancestor Africans (little diversity), and large sequence differ-
(MRCA) of the human mtDNA alleles has often been ences between these two sets of alleles (though this
referred to as “Mitochondrial Eve,” as if this were a pattern did not hold with additional sampling (Yu
particular person. Although it is true that modern and Li, 2000).
mtDNA alleles coalesced in an allele that existed in an In this sample of early studies, the different esti-
individual at the base of the tree, this individual was mates for the TMRCA and other patters in these
not the original individual that marked the beginning nuclear data sets were clearly heterogeneous, a pattern
of our species, nor was this individual alone during her that was noted at the time (Hey, 1997; Harris and Hey,
lifetime (Ayala, 1995). Every region of the genome has 1999a). Another conundrum was that the recombining
its own history, including its own MRCA. Indeed, there genomic regions did not all show the consistent evi-
is a male counterpart to the mtDNA MRCA – some- dence for the population expansions found in mtDNA
times named “Y chromosome Adam.” While regions and the Y chromosome (Harpending and Rogers, 2000;
that undergo recombination often have a more compli- Wall and Przeworski, 2000). At this time, only nuclear
cated tree structure of alleles, the most essential and microsatellite markers revealed evidence for such
critical idea is that every locus has its own history, recent expansions (Reich and Goldstein, 1998; Kimmel
including its own tree structure and its own TMRCA. et al., 1998; Zhivotovsky et al., 2000).
In neutral loci these features of a tree are a result of The heterogeneity in these studies was likely due to
the forces of mutation, population size, recombination, any of a number of reasons. Firstly, the effective popu-
linkage disequilibrium, and gene flow. Because these lation sizes of autosomes is four times higher than that
features are stochastic, even under the same demo- of the mtDNA and the Y-chromosome, and this pre-
graphic and evolutionary history different loci will dicts a four-fold longer expected time to a MRCA
have different TMRCAs and tree shapes. A simplified (three-fold for X-linked genes due to the hemizygous
example of a coalescent tree is shown in Figure 14.3. state for males). The older TMRCA for these data sets
Second, at the time of any gene0 s TMRCA, that particu- may be in line with the expectation from the Recent
lar allele exists within a population of alleles, i.e. group African Origin model (Ruvolo, 1996), although the
of humans. Given these caveats, and the fact that TMRCA for the PDHA1 alleles was exceptionally old.
mtDNA and Y-chromosome studies each reflect the Secondly, it may be the case that one set of the loci
evolution of a single locus, it is essential to analyze tree studied could be under some form of selection while
shapes, levels of diversity, and TMRCAs from a number others are reflecting primarily the demography of
human groups (Harris and Hey, 1999a; Harpending and the microcephalin locus (Evans et al., 2006). In
and Rogers, 2000; Przeworski et al., 2000; Wall and these loci, a highly divergent allele is present and
Przeworski, 2000). Selection is not only a concern for occurs most frequently outside of Africa, suggesting
mtDNA and Y-chromosome genes, but also for the a non-African root node. In other cases a very diver-
other nuclear loci because they were largely located gent and allele is present within Africa (Garrigan
within or near coding regions. Because of the potential et al., 2005a). These data sets have a host of possible
action of selection, it is difficult to resolve whether it is explanations. The microcephalin case may reflect the
the nuclear genes or the mtDNA and Y chromosome introgression of an “archaic” allele in the AMHS
genes that reflect demography at these loci. Thirdly, gene pool followed by locus-specific selective pro-
the cause of the discrepancy may be related to the cesses (Evans et al., 2006). One hypothesis is that the
mutation rate of the loci examined. Specifically, it “D” allele, which may be from an archaic human
could be the case the that rapid mutation rate of the population, confers a selective advantage related to
mtDNA and the microsatellites provided the resolution brain size causing it to spread in the modern gene
required to track recent demographic events, while the pool after introgression (Evans et al., 2006). However,
slower rate of mutations at SNP markers allowed only while this locus does play a role in microcephaly,
the tracking of older events. Despite the heterogeneity the precise phenotypic changes or selective advantage
in TMRCA and expansion estimates, the pattern of of extant human genetic variants is unknown (Mekel-
gene trees shapes being rooted mainly within Africa is Bobrov et al., 2007; Timpson et al., 2007). The other
consistent with an African origin for diversity and not a data sets have been explained by demographic models
Multiregional Continuity model (Takahata et al., 2001). that include admixture between AMHS and archaic
Given these issues, subsequent DNA-sequencing humans (Garrigan et al., 2005b; Garrigan and
projects targeted regions of the recombining nuclear Hammer, 2006; Cox et al., 2008), and/or significant
genome that were very likely to be neutral, and therefore population structure (meaning that the population
reflect demographic processes. In this light, Kaessmann was not one large panmictic population) in the early
et al. (1999) conducted a study of a 10 kilobase-pair AMHS gene pool (Shimada et al., 2007). Others ques-
intergenic, presumably neutral, X-linked region tion whether polymorphic chromosomal inversions
(Xq13.3) in 69 humans. They recovered a TMRCA at and selection may be creating a false signal of admix-
535 kya with the highest levels of diversity being seen ture (Reed and Tishkoff, 2006). Studies on the pat-
in African populations (Kaessmann et al., 1999). This terns of linkage disequilibrium in modern human
region also showed evidence for a population expansion populations also suggest some admixture between
(Kaessmann et al., 2001). humans and archaic populations (~5%) (Plagnol
There have been a number of subsequent DNA and Wall, 2006). More complex models that include
sequence studies of long (~10 kilobase pair) mainly multiple dispersals to and from Africa over the Pleis-
noncoding regions in humans. These include analyses tocene have also been forwarded to account for the
of chromosome 22 (Zhao et al., 2000), chromosome 1 variance in human population genetics data sets
(Yu et al., 2001), the X chromosome (Yu et al., 2002b), (Templeton, 2007).
and chromosome 6 (Zhao et al., 2006). These five data Direct genetic evidence from other hominins would
sets were summarized by Zhao et al. (2006) as tending be very helpful for distinguishing between the different
to support an “Out-of-Africa” model for human origins models of human evolution. Indeed, since the initial
rather than the Multiregional Continuity model. This publication of a Neanderthal mtDNA sequence (Krings
included greater African diversity, African alleles et al., 1997), sequences from these archaic humans
having a closer proximity to the root, an autosomal have been a critical part of the modern human origins
TMRCA of 860 kya, and a low autosomal effective debate. The collection of these sequences (and others)
population size (Zhao et al., 2006). Importantly, paris a testament to the power of PCR and other molecular
ticular aspects of the data sets suggested that these two genetics techniques to amplify and sequence DNA from
models were both too simple to account for all aspects ancient specimens (Pääbo et al., 2004). A Recent
of observed data, such as the old TMRCA estimates African Origin model suggests that Neanderthal
for non-African alleles and intermediate frequency mtDNA sequences would be significantly different
mutations outside of Africa (Zhao et al., 2006). from all AMHS sequences, while the Multiregional
Recent analyses of a handful of data sets are espe- Continuity model could potentially show Neanderthal
cially suggestive that simple models like Recent sequences to be nested within AMHS diversity.
African Origin and Multiregional Continuity hypoth- Over the last 10 years, the data obtained from
esis may not be sufficient to account for all aspects of ancient Neanderthal mtDNA are relatively unequivocal
the existing genetic data. These loci include the about structure of genetic relationships between
X-linked RRM2P4 region (Garrigan et al., 2005b; Cox Neanderthals and AMHS. The hypervariable mtDNA
et al., 2008), the Xp11.22 region (Shimada et al., 2007), sequence from the Neanderthal sample was
phylogenetically situated outside of an AMHS group 2007). These findings are consistent with the mtDNA
with a TMRCA about three times as deep as the deepest analyses.
AMHS node (Krings et al., 1999). Furthermore, the A recent analysis of unlinked nuclear loci has
Neanderthal sequence was about equally different recently been shown to strongly support a Recent
from all AMHS, showing no specific affinities with African Origin model without admixture (Fagundes
modern European sequences (Krings et al., 1997, et al., 2007). This analysis examined sequences from
1999). These sequences were augmented to recently 50 unlinked ~500 base-pair regions from three popula-
to six complete Neanderthal mtDNA genomes (Green tions (African, Asian, and Native American) (Fagundes
et al., 2008). This data set shows that humans and et al., 2007; Yu et al., 2002a). Using these data, a
Neanderthals form two distinct monophyletic clades number of models were assessed including African
separated from each other for at least 439 kya years replacement models, assimilation/admixture models,
(Briggs et al., 2009). and Multiregional Continuity models. An African
Although this is interpreted as suggesting that replacement model was strongly favored, with a
Neanderthals did not contribute to the AMHS gene “speciation time” of 141 kya for AMHS and a migration
pool, it has alternatively been suggested that the two from Africa at 51 kya. Fagundes et al. (2007) also
clade pattern at mtDNA is statistically compatible with showed that under some versions of an African
a scenario where AMHS and Neanderthals formed a replacement model for human origins, some old
merged population in the past, but the Neanderthal TMRCAs are expected, including genes that have their
mtDNA alleles were subsequently lost due to drift root outside of Africa. These findings may indicate that
(Nordborg, 1998). Simulations suggest that direct admixture is not necessary to explain data sets like
investigations of large numbers of ancient sequences RRM2P4 (Garrigan et al., 2005b) or Xp21.1 (Garrigan
from both AMHS and Neanderthals would be required et al., 2005a), whose patterns could be due to chance.
to refute a Neanderthal contribution to the modern Clearly, Fagundes et al. (2007) support a Recent
mtDNA gene pool (Nordborg, 1998; Serre et al., African Origin model, but with additional model com-
2004). While levels of admixture over 25% can be plexity in the form of large African population sizes
excluded, estimates below this number cannot despite and dramatic size changes outside of Africa.
the lack of direct evidence for admixture (Serre et al., In summary, the current wealth of data appears
2004). These admixture estimates are very conserva- to be most consistent with some form of a Recent
tive, and more complex scenarios that model popula- African Origin model for AMHS rather than a Multi-
tion interactions between humans and Neanderthals regional Continuity model (Tishkoff and Verrelli,
suggest that there was nearly no admixture (Currat 2003). However, the totality of these studies suggests
and Excoffier, 2004). that a simple “single ancestry” Recent African Origin
As learned during the human origin debate, model cannot explain the variance in the loci sampled
mtDNA represents a single locus and data from the (Garrigan and Hammer, 2006). Instead of a simple
nuclear genome is necessary to address questions Recent African Origin model, those that incorporate
more meaningfully. To this end, two large nuclear elements such as ancestral population structure in
DNA sequence data sets have been published from Africa, low levels of migration, and/or population
Neanderthal material (~1 million base pairs [Green expansions seem to fit the data best (Garrigan and
et al., 2006]; 65 250 base pairs [Noonan et al., 2006]). Hammer, 2006; Fagundes et al., 2007; Campbell and
These studies came to vastly different conclusions Tishkoff, 2008). Models that incorporate some level of
on the relationship of Neanderthals to AMHS. Specif- admixture between archaics and AMHS may also
ically, Noonan et al. (2006) supported significant prove useful (Garrigan and Hammer, 2006; Wall and
divergence between humans and Neanderthals while Hammer, 2006), although more data are required to
Green et al. (2006) supported a model where Neander- assess this effect more fully (Wall, 2000). In the future,
thals were within the range of diversity found within additional genetic data sets and analytical techniques,
modern humans. In a reanalysis of the data, Wall in conjunction with new material and interpretations
and Kim (2007) showed that the sequences of from the paleontological record, will be required for
Green et al. (2006) reflected either the inclusion further refining and advancing our understanding of
of contaminant DNA sequences or sequencing errors modern human origins.
in the analysis. Considering only the Noonan et al.
(2006) data, the TMRCA between humans and
Global patterns of human migration
Neanderthals was 706 kya, a population split occurred
and gene flow
at ~350 kya, and the most likely amount of admixture
between humans and Neanderthals was estimated to Many aspects of human migration are implicit in the
be 0%, although the confidence interval spanned study of modern human origins, such as the movement
0–20% (Noonan et al., 2006) or 0–39% (Wall and Kim, of humans out of Africa and across the world. Studies of
DNA markers have been utilized extensively to directly Because it provides the most explanatory power in
examine the relationship between genetic diversity and generating correlations, Africa was indicated as the
geography. DNA markers have been used to explain the likely source population. This Serial Founder Effect
general, large-scale patterns of human migrations, such model explains up to 78% of the variation between
as the out of Africa migration event that is part of the genetic differences between populations (this value
Recent African Origin model. These markers are also comes from the R2 estimated for the model), suggest-
used to explain more specific instances of migrations, ing that the remaining variation can be explained by
such as the peopling of the Pacific or Iceland. These population-specific factors, such as drift and selection
questions most specifically relate to the relationship (Ramachandran et al., 2005).
between genetic diversity and geography. Models that estimate time in the context of
However, at the lower levels “migration” is also syn- this data set show a population-size expansion begin-
onymous with gene flow or admixture, the movement of ning at about 56 kya from a very small founding popu-
alleles between populations. This has also been impli- lation (~1000 individuals) in East Africa (Liu et al.,
citly discussed, for example in the potential cases of 2006). This date is generally consistent with the
admixture between archaics and AMHS, which consti- TMRCA estimates for the non-African portions of
tutes a degree of gene flow between these populations. allele trees and the evidence from mismatch distribu-
Studies of DNA markers have been utilized extensively tions summarized above. Similar studies based on dif-
to examine gene flow in the form of differences in pat- ferent markers, estimates of genetic differentiation,
terns of gene flow between males and females and pat- and/or geographic modeling provide qualitatively simi-
terns of gene flow between human populations. lar results (Manica et al., 2005; Prugnolle et al., 2005;
The relationship of genetic diversity and geography Ray et al., 2005; Jakobsson et al., 2008; Li et al., 2008;
is critical for understanding fine-scale population gen- Tishkoff et al., 2009).
etic questions. At classical marker loci, it has long been Interestingly, some analyses of large-scale
noted that human polymorphisms generally behave in microsatellite data suggest that humans form discrete
a pattern where genetic distance and geographic dis- clusters that corresponded to geography (Rosenberg
tance are positively correlated and that gene frequen- et al., 2002). The cause of this pattern was quickly
cies change clinally (Cavallli-Sforza et al., 1994). This debated, perhaps due to the possible implication that
pattern is generally referred to as “isolation by dis- this pattern was an affirmation of human “races” (e.g.,
tance” which suggests that human migration patterns Serre and Pääbo, 2004). One suggestion was that the
are related to genetic distance, and that matings pre- discontinuous sampling regime of human groups in
dominantly occur over short distances. Interestingly, this study led spuriously to this result (Serre and
variation in cranial morphological data is in agreement Pääbo, 2004). Alternative explanations suggest that
with classical markers and microsatellites, all being the relationship between genetic and geographic dis-
consistent with isolation by distance models at global tance is largely clinal, yet has patterning that can be
scales (Relethford, 2004). attributed to minor but real differences in geography
A number of studies have recently re-examined the (Rosenberg et al., 2005).
general patterns of human geography and genetic Hunley et al. (2009) recently crystallized these stud-
diversity using large sets of neutral DNA markers. ies into four different models for the relationship
Ramachandran et al. (2005) examined a global micro- between genetic and geographic distance in humans.
satellite marker data set from 1027 diverse humans These models include independent regions (i.e., each
(Cann et al., 2002; Rosenberg et al., 2002) and com- geographic region evolves independently), isolation by
pared pairwise genetic distances between populations distance (described above), serial founders (described
(using FST, an index of genetic differentiation between above), and nested regions. In a nested region model,
groups) using “great circle” distances between popula- non-African diversity is represented by an increasingly
tions and “waypoint” distances, i.e., distances that used reduced set of alleles with increasing distance from
more realistic migration paths between points (e.g., Africa (Tishkoff et al., 1996) based on a mix of bottle-
requiring Egypt to connect points between Africa and necks and expansions. Comparing simulations under
Asia). These models produce high correlation coeffi- each model with the pattern observed from a 783
cient (R2) values of 0.59 and 0.78, respectively, showing microsatellite marker data set including 1032 humans
that these genetic and geographic distances are closely (Cann et al., 2002; Rosenberg et al., 2005) showed that
related. none of these models explained the totality of the data.
Given the nonequilibrium nature of the human Their preferred model includes a combination of serial
populations, this relationship was interpreted as a founding, bottlenecks, migrations, and gene flow
“Serial Founder Effect,” a model where humans origin- (Hunley et al., 2009). In other words, a migration scen-
ated from a single source, with successive migrations ario that is considerably more complex than any of
sampling from its most recent source populations. the ones previously suggested. However, the overall
pattern from these studies remains consistent with a Because the Y chromosome reflects a paternal
Recent African Origin model for human origins and inheritance pattern, this finding suggested differences
dispersal. in aspects of demography between males and females.
Finer-scale examination of DNA markers can Seielstad et al. (1998) showed that sex differences
assist in making further refinements of the migration in migration rate best explained the data and reflect
of humans throughout the globe. Targets of study an overall patrilocal pattern for humans, i.e., that
have included regional migration events, such as the women moved further than men to mate and repro-
original migration out of Africa. For example, similar duce. This patrilocal tendency is supported by the
to studies of human origins, the ages of particular ethnographic record (Murdock, 1967) and is consistent
nodes have been used to date the out-of-Africa migra- with other global studies of human Y-chromosome and
tion, using the TMRCA of the non-African alleles mtDNA markers (Wilder et al., 2004b). However, a
within the trees. Based on the TMRCA of non-African resequencing study of 389 humans from 10 popula-
mtDNA genomes, two estimates for an out of Africa tions showed no differences in within group variation
migration are 94 kya (Gonder et al., 2007) and 52 kya at Y chromosomes versus mtDNA, calling this result
(Ingman et al., 2000). The Y chromosome yields into question (Wilder et al., 2004a). Markers from
younger estimates for non-Africans, e.g., 40 kya, mtDNA and Y chromosome may not exclusively trace
(Thomson et al., 2000). Autosomal studies generally demography because of the potential confounding
agree with these estimates (Fagundes et al., 2007). action of selection.
Other studies have directly addressed the geography Examination of neutral markers on autosomes
of the migration routes out of Africa (reviewed in Reed versus the X chromosome can potentially circumvent
and Tishkoff, 2006). these problems (Ramachandran et al., 2004; Wilkins
Many other migration events also have been inves- and Marlowe, 2006). This is because autosomes
tigated. Two events that have received a great deal of are found equally in males and females, while
study are the peopling of the Americas (reviewed X chromosomes spend more time residing in females,
in Dillehay, 2009) and the peopling of the Pacific on average. Also, both genome compartments recom-
(Friedlaender et al., 2008; Kayser et al., 2008a, bine, mitigating the effect of selection on linked sites.
2008b). Other studies have focused on understanding In X chromosome versus autosome comparisons,
the relationships of population movements within con- examination of microsatellite markers demonstrated
tinents, e.g., Africa (Reed and Tishkoff, 2006; Tishkoff no differences between these compartments
et al., 2009). Even more fine-scale studies have focused (Ramachandran et al., 2004) while SNP markers sug-
on the peopling of particular islands, such as Iceland gested a model in which genetic drift has actually been
(Helgason et al., 2009), and the origins of particular stronger on the X chromosome perhaps due to selection
human populations, such as the Lemba, a South or high long-range male migration after leaving Africa
African group with ancestral ties to the Near East (Keinan et al., 2009). In contrast, Hammer et al. (2008)
(Thomas et al., 2000). Lastly, genetic research using used a resequencing strategy and recovered higher
molecular markers has allowed for greater understand- levels of X-chromosome diversity. This was interpreted
ing of historical movements of people and admixture by the authors to be caused by polygyny0 s effects on
between human groups (e.g., Alves-Silva et al., 2000; male reproductive variance, which can act to lower
Quintana-Murci et al., 2004; Tishkoff et al., 2009). males0 effective population size relative to that of
Sex-specific gene flow within and between popula- females. However, this result is also consistent with
tions plays an important role in shaping local patterns higher rates of female migration (Hammer et al., 2008).
of human genetic diversity. In an analysis comparing One of the main problems with ascertaining the
the diversity between nuclear, mitochondrial, and effect of residence patterns in humans may be our
Y-chromosome-linked DNA markers in humans, flexible social structure. As Wilkins and Marlowe
Seielstad et al. (1998) demonstrated a pattern in which (2006) pointed out, while most current human groups
Y-chromosome markers showed markedly reduced are patrilocal, this may reflect recent changes. Over the
diversity within populations compared to autosomal course of human history our residence patterns may
makers and mtDNA (35.5% for Y chromosomes vs. have followed that of current forager populations, who
~81–86% for autosomes and mtDNA). Furthermore, may be best represented as bilocal (Marlowe, 2004).
there were more genetic differences between popula- This historical difference may help explain the differ-
tions at Y-chromosomes DNA markers than mtDNA or ences in the global studies cited above (Wilkins and
autosomal markers (Seielstad et al., 1998). This means Marlowe, 2006), and further suggest that recent mating
that there are greater differences at the Y chromosome and residence patterns have a stronger effect on
between populations, i.e., the Y-linked diversity is diversity.
more geographically restricted than autosomes and Indeed, at the local level, the relationship between
mtDNA markers. sex-specific migration/residence patterns and genetic
diversity appears to have a stronger relationship to us from our closest living relatives, the apes, and our
cultural practices. For example, Oota et al. (2001) fossil ancestors. The study of DNA markers has been
examined mtDNA and Y-linked markers within three used to investigate the molecular causes of these
patrilocal and three matrilocal populations in phenotypic differences between humans and nonhu-
Thailand. These populations fit the predictions of the man primates. Phylogenetic comparisons between
sex-biased migration model, with the patrilocal popu- human genes and their orthologs (genes that are iden-
lations having low diversity on Y markers and high tical by descent) in chimpanzees and other mammals
diversity at mtDNA markers. This finding is supported have been widely employed in the search for the bases
by data from other populations (e.g., Chaix et al., 2004; of human uniqueness. These interspecific comparisons
Destro-Bisol et al., 2004; Bolnick et al., 2006). search for two main classes of evolutionary changes:
Interestingly, further studies have shown differ- those in protein-coding regions (i.e. genes) and those in
ences between exogenous populations, in which mar- noncoding regions.
riage partners can be drawn from outside the Studies on protein-coding genes have focused on
population, and strictly endogenous populations, in uncovering instances of molecular adaptation
which marriage partners are drawn only from within along the human lineage. Positively selected genes
the population (Kumar et al., 2006). In endogenous are those that show evidence of more amino acid
marriages, differences between mtDNA and Y-chromo- change than expected, deciphered from comparisons
some diversity are not expected to accrue, resulting in of the rates of change in nonsynonymous codon sites
no differences between patrilocal and matrilocal popu- versus synonymous sites (commonly referred to as
lations (Kumar et al., 2006). Analysis of endogenous the Ka/Ks ratio, the dN/dS ratio, or o) (Kimura, 1977;
groups from India reflect this expectation (Kumar Miyata et al., 1980). These comparisons have been
et al., 2006). Local-scale studies have also used done in “candidate genes,” i.e., those with a priori
X chromosome versus autosome comparisons to dem- evidence for a relationship to the human phenotype.
onstrate that patrilineal herders have more female Candidate gene studies for human molecular adapta-
migration and higher female effective population size tion have included genes relating to brain size (e.g.,
than bilineal groups (Ségurel et al., 2008). ASPM [Zhang, 2003; Evans et al., 2004; Kouprina
In summary, migration, gene flow, and geography et al., 2004]) and language (e.g., FOXP2 [Enard et al.,
all have had an effect on human genetic diversity. DNA 2002]). In both of these genes positive selection was
markers show that genetic and geographic distances demonstrated along the human lineage. Scans for
are strongly correlated globally (Ramachandran et al., selection have also been done at the genomic level,
2005), although the exact model underlying this correl- comparing thousands of coding regions among
ation is complex (Hunley et al., 2009). At the global mammalian species (Clark et al., 2003; Chimpanzee
scale, human residence patterns may play a role in Sequencing and Analysis Consortium, 2005; Arbiza
patterning human diversity (Seielstad et al., 1998), et al., 2006; Bakewell et al., 2007; Rhesus Macaque
although the effect is debated (Wilder et al., 2004a). Genome Sequencing and Analysis Consortium, 2007;
However, at the local level human mating patterns Kosiol et al., 2008). (Access to genome data is available
appears to strongly influence genetic diversity (e.g., at the UCSC Genome Browser http://genome.ucsc.edu
Oota et al., 2001). [Kent et al., 2002].)
Some genomic analyses show that genes that
are positively selected along the human lineage
DNA markers and natural selection
(called positively selected genes or PSGs) are enriched
Natural selection is the evolutionary force responsible for biological mechanisms related to immune
for generating adaptations. Natural selection works via defense, sensory perception, reproduction, and cancer
differential reproductive success that covaries with processes (apoptosis, cell cycle control, and tumor
genetic variation. Humans have many unique traits suppression) (Clark et al., 2003; Nielsen et al., 2005;
that are thought to be adaptations, such as language, Bakewell et al., 2007; Kosiol et al., 2008). However,
encephalized brains, bipedal locomotion, and oppos- there are a few interesting findings from these
able thumbs with precision grip. Adaptive traits such comparative genomic studies. Firstly, thus far, the pro-
as these are often held up to be what has “made us cesses that have been identified in these genomic scans
human” (Varki and Altheide, 2005) and, as such, have do not seem to correspond to the phenotypic features
been the focus of considerable investigation. Humans classically considered to be the hallmarks of our
also differ from our living primate relatives in other species. Secondly, one study reported few PSGs exclu-
ways, for example, in disease susceptibility (Varki and sive to the human lineage (7 out of 17 489 orthologs
Altheide, 2005). These adaptive traits were fixed by [Kosiol et al., 2008]). While this may be related to the
natural selection in the human lineage. Therefore, they low power of the statistical tests used, it nevertheless is
have limited variance among humans and differentiate surprising that so few genes have undergone selection
exclusively in humans. Thirdly, there are more PSGs Understanding the role of selection at genes within
found on the chimpanzee lineage than the human lin- a species is a population genetic question that is intim-
eage (Bakewell et al., 2007). These results are surpris- ately tied to understanding the population genetics of
ing because the hominin lineage is a great deal more neutral DNA markers, described above. Essentially,
derived than the chimpanzee lineage. As of yet, there is understanding the role of selection at particular genes
no dramatic genomic signature in protein-coding often relies on different methodological comparisons
genes documenting human uniqueness. to the diversity present in neutral genes, where diver-
Other studies have comparatively examined non- sity is due to demographic processes (Kreitman, 2000;
coding regions of the genome for evidence of natural Bamshad and Wooding, 2003; Harris and Meyer,
selection. The main rationale for these studies is the 2006; Sabeti et al., 2006). For example, a locus that
hypothesis that the majority of human phenotypic evo- has two alleles under balancing selection is likely to
lution is caused by regulatory change, not by protein be more diverse and have an older TMRCA than a
change (King and Wilson, 1975). To this end, studies neutral locus, because selection preserves these alleles
have looked for rapidly evolving noncoding regions on in the gene pool, allowing them to build more diversity
the human lineage (Prabhakar et al., 2006). An excess through mutations and a longer genealogical history
of human-specific accelerated noncoding regions have than expected (human example: CD209L [Barreiro
been found near genes involved in neuronal function, et al., 2005]). In contrast, an allele at a locus that is
although the chimpanzee lineage has a similar pattern being swept rapidly through a population due to selec-
(Prabhakar et al., 2006). Indeed, human accelerated tion will have lower diversity, high linkage disequilib-
regions may have a function in gene expression rium, and a shallower TMRCA than at neutral loci
(Bird et al., 2007). One particular region stands out as (human example: the lactase gene (LCT) [Bersaglieri
particularly interesting. This is human accelerated et al., 2004; Tishkoff et al., 2007]). In genes that are
region 1 (HAR1), which is a 118 base-pair region that undergoing local adaptation, selected loci will show
appears to be undergoing exceptionally accelerated more genetic differentiation between populations than
change in the human lineage (Pollard et al., 2006). will neutral loci (human example: pigmentation genes
HAR1 is part of an RNA gene expressed in the develop- [Norton et al., 2007]). In each case, neutral loci set the
ing human brain suggesting a role in human brain size expectations for diversity, which is why they are crit-
(Pollard et al., 2006). Additional work on other human ical to understanding whether genes are under natural
accelerated noncoding regions is likely to provide con- selection.
siderable insight into the evolution of the human Similar to the genomic scans for interspecfic cases
phenotype. of natural selection, there have been many studies
Numerous studies have also looked for selection mining genomic-scale human population genetics data
in the form of highly conserved noncoding regions, sets for evidence of selection (a recent review examined
under the assumption that conserved regulatory 21 population genomics scans in humans [Akey,
elements are likely to be functionally important 2009]). Furthermore, there is currently a wealth of
(Dermitzakis et al., 2003; Bejerano et al., 2004). Stud- different methods that ascertain deviations in genomic
ies of these noncoding conserved regions demonstrate data from the neutral expectation in different ways
that they are indeed functional (Woolfe et al., 2005) (Sabeti et al., 2006; Akey, 2009). For example, some
and these regions are constrained within humans scans detect selection by finding unusually long
(Drake et al., 2006). haplotypes (Sabeti et al., 2002b, 2006; Voight et al.,
While these PSGs, human accelerated regions, and 2006). When a positively selected allele spreads rapidly
conserved noncoding regions are common to nearly all to fixation in a population, many linked sites extending
humans, other features that are hypothesized to be in both directions from the selected site also spread in
under selection are variable within our species. These the population as an extended haplotype. Eventually
include traits that vary in humans throughout the recombination “breaks up” a long haplotype, but for a
globe, such as body size and proportions (Katzmarzyk period of time it remains in the population as a signal
and Leonard, 1998), skin color (Jablonski and Chaplin, of positive selection.
2000), lactase persistence (Swallow, 2003), susceptibil- Sabeti et al. (2007) examined over three million
ity to infectious disease (Hill, 2006), and others covered SNP markers and found over 300 of these “candidate”
in this volume. In general, many of these are thought to regions. Further refinements revealed genes under
be adaptive responses to different the climatic, dietary, selection were related to lactase persistence, skin color,
and infectious environments that occur throughout and viral diseases (Sabeti et al., 2007). Akey (2009)
the globe. Furthermore, selection has also acted differ- recently collated results from 9 human population
ently on humans over time, both before and after the genomic scans for selected regions and found 5110
shift to agriculture (Livingstone, 1958; Armelagos and total regions under selection. Surprisingly, only
Harper, 2005). 722 (14.1%) of these putatively selected regions were
discovered in more than 1 of the 9 studies. While these evidence for natural selection acting on two erythro-
722 regions contained genes that are known to be cyte related genes b-globin and a-globin, and a novel
under selection (e.g., LCT), there were also a consider- candidate locus from the immune system (CD40L).
ably number of novel loci such as genes involved in The hemoglobin protein is a tetramer comprised of
cochlear function (Akey 2009). two a- and two b-chains that carries oxygen and carbon
Before the advent of genomics, the ascertainment dioxide to and from tissues. This tetramer fills red
of natural selection relied on the “candidate gene” blood cells. Carriers for the HbS allele are semipro-
approach, which examined the population genetics of tected against death from malarial infection (Allison,
loci suspected to be under selection a priori. These 1954), although individuals heterozygous for HbS can
hypotheses can be derived from genes suspected to be have sickle-shaped red blood cells. The HbS allele is
under selection based on classical markers, studies of common throughout Africa, southern Europe, and
disease distributions, and/or from suspected selective South Asia.
agents. One of the most well-known selective agents DNA marker studies of the b-globin gene have pro-
suspected to be acting on classical loci, DNA marker, duced a number of interesting findings from a number
and disease polymorphism is malaria (Allison, 1954, of different parts of the world. Although all HbS alleles
1961; Kwiatkowski, 2005). The disease has a tropical have the same mutation, which affects the sixth amino
and subtropical distribution that currently includes acid, this same change has occurred on a number of
109 countries in Africa, the Middle East, Asia, and different haplotypes. Using RFLP markers, Pagnier
the New World (World Health Organization, 2008). et al. (1984) showed that the HbS mutation occurred
Annually, about 247 million humans contract malaria on at least three different haplotypes in Africa, and
and it causes 1 million deaths, mainly in children Kulozik et al. (1986) found an additional origination
under 5 years of age (World Health Organization, in Asia. This shows that the mutation has occurred
2008). The major parasite responsible for mortality is multiple times, and despite its apparent selective cost,
Plasmodium falciparum, though the P. vivax parasite each time increased in frequency due to its protective
is also responsible for a large number of cases of ill- effects against malaria. Furthermore, at least one of
ness, especially outside of Africa (Mendis et al., 2001). the HbS mutations is apparently recent, having
(See Chapter 27 of this volume for a more complete occurred less than 2100 years ago (Currat et al.,
discussion of human malaria.) 2002). Single nucleotide polymorphism studies of HbS
Livingstone (1958) suggested that malaria was a alleles show that linkage disequilibrium extends for
recent selective agent connected to agriculture, which over 400 kilobases across a recombination hotspot
caused changes in land use, increasing both mosquito (Hanchard et al., 2007).
habitat and population density. These features allowed Other hemoglobin alleles have more recent origins.
malaria to become a selective agent, which subse- The HbC allele is common in West Africa and is semi-
quently gave rise to an increase in sickle cell anemia protective against death from malarial infection
(Livingstone, 1958). For these reasons the population (Modiano et al., 2001). This allele has an origin within
genetics of human malaria resistance has been exten- 5000 years as well as extended linkage disequilibrium
sively studied at candidate loci in many populations of consistent with natural selection (Wood et al., 2005).
humans around the globe. These studies provide sub- The HbE allele, common is Southeast Asia, is protective
stantial evidence for the action of natural selection on against malaria (Chotivanich et al., 2002). The HbE
modern humans. is also inferred to have arisen more than once in
Based on a review of early classical marker and Southeast Asia and Europe (Kazazian et al., 1984).
epidemiological studies, Allison (1961) provided evi- A microsatellite analysis of a single HbE type showed
dence for a relationship between malaria and multiple extended linkage disequilibrium and an origin for the
b-globin gene alleles (HbS, HbC, and HbE), thalassemias allele within the last 4400 years (Ohashi et al., 2004).
(deficiencies in the production of the a- and b-globin The recent origin of all of these alleles is strongly
genes), and G6PD enzyme deficiencies. Similar rela- consistent with Livingstone0 s (1958) “agriculture
tionships were hypothesized between malaria and hypothesis” for malaria.
Southeast Asian ovalocytosis (the SLC4A1 gene) Mutations in the a-globin genes also show evidence
(Serjeantson et al., 1977) and Duffy blood group nega- for malarial selection. Humans have two identical
tivity (the FY gene) (Miller et al., 1976; Livingstone, a-globin genes arranged in tandem. The major muta-
1984). These studies, and others, provided a host of tions in a-globin are whole gene deletions, not amino
“candidate genes” for examination by DNA markers. acid replacements. These deletions cause a reduction
It is worth noting that many of these genes have in a-chain production, resulting in a disease called
extreme medical importance, which has led to a-thalassemia. Flint et al. (1986) investigated the dis-
direct clinical investigations studying their effects tribution of a-globin gene deletions and malaria in
(Kwiatkowski, 2005). Here, I will review the inferential Melanesia using RFLPs. They found that the
frequency of a-globin deletion alleles was higher in within these regions were previously known to be
coastal Papua New Guinea (which has higher rates under selection, while others are novel. One of the
of malaria) than highland Papua New Guinea (which strongest, most well-documented selective forces
has low rates of malaria). Within Melanesia, a clinal acting on humans is malaria. In response, natural
latitudinal gradient was found both for malarial selection has shaped the evolution of a number of
endemicity and the frequency of a-globin deletion genes in populations across the globe. Future research
alleles. These relationships did not hold for other that links comparative genomics, population genetics,
markers. These findings strongly supported a link and functional studies are likely to provide consider-
between malaria and a-thalassemia in Melanesia. able insight into the action of natural selection on
The exact mechanism for protection, however, is not many human traits, those that vary both interspecifi-
yet fully understood (Kwiatkowski, 2005). cally and intraspecifically.
CD40L is an X-linked gene that encodes the
CD40 ligand protein and plays a crucial role in the
immune system, facilitating immunoglobulin class THE APPORTIONMENT OF HUMAN
switching. Mutations in this gene can lead to X-linked VARIATION
hypergammaglobulinemia (XHIM) (Allen et al., 1993)
leaving individuals immune deficient and susceptible One of the most interesting aspects of human popula-
to recurrent infections from pathogens such as tion genetics relates to the apportionment of human
Pneumocystis carinii and Cryptosporidium (Levy diversity. These studies address what amount of the
et al., 1997). A SNP marker in the CD40L promoter total variation present in the human species is appor-
region has been shown to ameliorate malaria in tioned at lower levels. In human studies, these levels
Gambian males (Sabeti et al., 2002a). Subsequent have most often related to that of “race” and “popula-
analysis of this SNP marker allele showed that the tion.” Occasionally, “geographical region” (e.g., contin-
allele was present at high frequency on Africa and ent) has been used as a proxy for levels of diversity
at much stronger linkage disequilibrium than other above population.
SNP markers (Sabeti et al., 2002b). This allele is The most important analysis of the apportionment
inferred to be about 6500 years old (Sabeti et al., of human diversity remains Lewontin0 s (1972) seminal
2002b). Interestingly, the molecular mechanism of analysis of classical marker polymorphisms. His study
this protective allele is not currently known, and it compiled polymorphism data from 17 classical loci
remains to be shown what particular genes in this from a number of human studies to estimate the
large haplotype have a direct role in malarial adapta- degree of variation within and between human popula-
tion (Sabeti et al., 2002a). tions, and races within the species as a whole. In this
Studies of DNA markers in human populations study, “population” was a group of individuals with a
have also inferred selection acting on other candidate shared language or cultural identity, e.g., Navajo from
genes involved in malarial resistance. These include North America, Luo from Africa, and Basque from
SLC4A1 (the basis for the Diego blood group) (Wilder Europe. The particular “race” classification chosen by
et al., 2009), GYPA (the basis for the MN blood group) Lewontin had seven categories. The results across
(Baum et al., 2002), and G6PD (a red blood cell loci showed that 85.4% of total human diversity was
enzyme) (Tishkoff et al., 2001). due to individual variation within a population. The
Natural selection is the force of evolution that differences between populations – but within a “race”
creates adaptations. Analyses of humans and other category – accounted for an additional 8.3% of the
primates have demonstrated the action of selection variation. Together, these number account for 93.7%
on candidate loci for uniquely human traits (e.g., of total human diversity within race categories, appor-
Zhang, 2003; Evans et al., 2004; Kouprina et al., tioning only 6.3% of the variation to differences
2004). Comparative genomic scans, on the other hand, between race categories (see Chapter 15 of this volume
have found few genes under natural selection at the for further discussion).
protein level in humans overall (Kosiol et al., 2008), This finding was replicated in other classical
and when compared to chimpanzees (Bakewell et al., marker studies (e.g., Ryman et al., 1983). This appor-
2007). Comparisons of noncoding regions are sugg- tionment of human diversity strongly argued against
estive that some unique human traits may be affec- typological models for human racial classification.
ted by differences in gene regulation (Pollard et al., Because classical marker loci can potentially be influ-
2006), consistent with earlier hypotheses (King and enced by natural selection, subsequent DNA marker
Wilson, 1975). studies were critical for providing an additional
Within the human species, genomic analyses have window onto the apportionment of genetic diversity.
provided evidence that a number of regions are under One of the first studies to employ DNA markers to
natural selection (Akey, 2009). Some of the genes assess the apportionment of human diversity examined
mtDNA RFLPs (Excoffier et al., 1992). This study com- 2. How would low levels of admixture between archa-
piled data from 34 RFLP sites from 2 populations ics and anatomically modern humans change our
from 5 regions (akin to race categories) of the globe understanding of human origins? Would there be
(10 total populations). Their hierarchical analysis implications for human taxonomy? What about no
found that between 75% and 81% of the diversity was admixture? Or high rates of admixture?
found within the population variance component 3. What are the expectations for comparative levels of
and between 16% and 22% was apportioned between mtDNA, X-linked, and Y-linked genetic diversity in
the 5 regions. Subsequent analysis of DNA sequences groups for the different residence patterns and
from the mtDNA “hypervariable” regions recovered social structures commonly found in humans and
similar findings (Jorde et al., 2000). While widely used other primates (i.e., patrilocal/virilocal, matrilocal/
as a molecular marker, mtDNA has some properties uxorilocal, bilocal, male philopatry, female philo-
that make it unique, as discussed above. patry, monogamy, polygyny, polyandry)?
Study of the nuclear genome can examine larger 4. How does the study of natural selection on simple
numbers of independent loci, thus providing a more genetic traits, e.g., b-globin, relate to the role of
comprehensive view of the apportionment of human natural selection in shaping complex polygenetic
diversity. Barbujani et al. (1997) studied a total of traits, e.g., body size?
109 nuclear autosomal RFLP and microsatellite loci,
reflecting a four-fold increase over the number of
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15 Ten Facts about Human Variation
Jonathan Marks
INTRODUCTION group, and religious group, respectively. Race was

taken to inhere in an individual, as a group quality
The idea of race, so intrinsic a part of American social producing a specific identifiable form and expression
life, is a surprisingly ephemeral one. The ancient world in different people. Even so recent a scholar as the
conceptualized human diversity in purely local terms, Harvard physical anthropologist Earnest Hooton
and the idea that the human species could be naturally (1926) could think of race as something to be diag-
partitioned into a reasonably small number of reason- nosed, on a medical analogy.
ably discrete kinds of people does not seem to have By the early 1930s, partly in response to the rise of
been seriously entertained until the late seventeenth racist ideologies in Europe, the concept of race under-
century (Hannaford, 1996; Hudson, 1996; Jahoda, went a revision. It became a group of people, a popula-
1999; Stuurman, 2000). The term “race” was intro- tion, rather than an inner quality or spirit. This
duced into biological discourse by Buffon in the eight- reversed the locus of race; instead of a race residing
eenth century, but he used the term in an entirely within a person, a person would now be a part of a
colloquial, not taxonomic, way. In this sense the term race. Further, the laws of genetics did not seem to
meant the equivalent of a “strain” or “variety” – a group permit anything to be transmitted as race was thought
of organisms linked by the possession of familial fea- to be. What would be “passing” to the previous
tures. Buffon’s rival Linnaeus, the founder of modern generation – pretending to be a race you really were
taxonomy, divided humans into four geographical not – would be merely the facts of complex ancestry, or
subspecies – although he did not call them “races.” euphemistically, “gene flow,” under the new concept.
The succeeding generation fused Buffon’s word with Finally, an appreciation for the significance of cultural
Linnaeus’s concept, and thus created the scientific distinctions in maintaining boundaries between
term “race,” used well into the twentieth century. human groups made it necessary to distinguish
The Linnaean concept of race, however, was a Pla- between ostensibly biological units of the human
tonic or essentialist idea – describing not a reality (how species, and culturally constituted group differences,
organisms are), but a hyper-reality (the imaginary and to juxtapose the latter category of human diversity
form they represent). Thus, Linnaeus (1758, p. 21) against the study of race; it would be come to be known
defined “Homo sapiens Europaeus albus” – that is to as “ethnicity.”
say, white European Homo sapiens – as having long Physical anthropology, like human genetics, had to
“long flowing blond hair” and “blue eyes” (Pilis flaves- reinvent itself after World War II, since it was in fact
centibus prolixis. Oculis caeruleis). Even taking account not terribly easy to distinguish the good American
of the fact that Linnaeus did not much travel outside of science of race from its evil Nazi counterpart. Hooton
his native Sweden, it is difficult to imagine him being had tried to do so as early as 1936, publishing an
that naı̈ve. Linnaeus clearly was describing an ideal indignant review article in Science as “a physical
type, a metaphysical form, not the actual indigenous anthropologist, who . . . desires emphatically to disso-
inhabitants of Europe. ciate the finding of his science from the acts of human
The essentialized race was not necessarily limited injustice which masquerade as ‘racial measures’ or
to the continents. Since it was not an empirical concept ‘racial movements’ ” (Hooton, 1936, p. 512).
to begin with, it could be easily extended to any group Hooton, however, was unsuccessful. A “new”
of people with a distinct identity. Thus, one could just physical anthropology (Washburn, 1951) would study
as readily talk about the “Aryan race,” the “French human adaptation and microevolution, which was
race,” or the “Jewish race,” even though the terms local, not continental. The human species would
technically applied to a linguistic group, national now be seen “as constituting a widespread network of
265
266 Jonathan Marks
more-or-less interrelated, ecologically adapted and To understand race properly, however, we must
functional entities” (Weiner, 1957, p. 80). appreciate that it is a biocultural category, the result
The Civil Rights movement precipitated a second of a negotiation between patterns of difference and
revision of the ontology of race for physical anthropol- perceptions of otherness. Old categories of identity
ogy. If the units of the human species were indeed local are obliterated, or are relegated to “ethnicities” rather
populations, then higher-order clusters of populations than to “races,” (Igntiev, 1996; Brodkin, 1999) and
could now be recognized as arbitrary and ephemeral newer, more politically salient categories become
(Thieme, 1952; Hulse, 1962; Johnston, 1966). Thus racialized. Notably, the 2000 US Census separated the
Frank Livingstone could epigrammatically declare, question of “Spanish/Hispanic/Latino” from that of
“There are no races, there are only clines” (1962, p. 279). “race” on the quite sensible grounds that “Spanish/
Of course, there was the embarrassment of having Hispanic/Latino” designates a linguistic category, and
the President of the American Association of Physical thus cross-cuts race. One could, after all, reasonably
Anthropologists (Carleton Coon of the University of fall within that category with mostly Native American
Pennsylvania, Earnest Hooton’s second doctoral stu- Ancestry, mostly Filipino ancestry, mostly southern
dent at Harvard) colluding with the segregationists in European ancestry, mostly Afro-Caribbean ancestry,
1962, but Coon stood alone in defending the segrega- and most especially, a mixture of several of those. Then
tionist literature from censure by the American Associ- the Census provided the familiar choices in the “race”
ation of Physical Anthropologists (Coon, 1981; Lasker, question (White, Black, Native American, Asian, and
1999). The “new physical anthropology” gave practi- Pacific Islander), but also included the option “Some
tioners leeway to abandon race to the cultural anthro- other race.” That choice, “Some other race,” was
pologists and sociologists on one side (as ethnicity), checked by 42% of self-identified Hispanics, but by
and to the population geneticists (as science) on the only a negligible amount of non-Hispanics. It seems
other. Thus, widely used biological anthropology texts, that the Census Bureau over thought the matter:
such as Frank Johnston’s (1973) Microevolution of Hispanic has effectively become “some other race” –
Human Populations and Jane Underwood’s (1979) the cultural basis of its demarcation notwithstanding
Human Variation and Human Microevolution could (Mays et al., 2003).
get by without even mentioning race in the index. Population geneticists have not been able to resolve
Population geneticists, however, were actually race because it is not a genetic category (Graves, 2004).
multivocal about race. On the one hand, Lewontin’s Race is a human group which, like all human groups
(1972) famous “The apportionment of human diver- down to “family,” is a coproduction of historical/cul-
sity” was able to quantify what fieldworkers had long tural processes and of microevolutionary biological
known: there are all kinds of people, everywhere. processes. It not a question of whether humans differ,
Lewontin’s discovery that there is approximately six but of how they do so, and of how we concurrently
times more within-group variation than between- make sense of it. And any scientific sense we make of
group variation detectable in the human species human variation must ultimately by consistent with 10
seemed to put the lie to any possibility that the human empirical generalizations produced by anthropology
species could be naturally divided into a small number and genetics over the last century and a half.
of relatively discrete gene pools. On the other hand,
other population geneticists would use races as natural
categories quite unproblematically and unreflectively 1. HUMAN GROUPS DISTINGUISH
(Cavalli-Sforza, 1974; Nei and Roychoudhury, 1974). THEMSELVES PRINCIPALLY CULTURALLY
By the 1990s, race was undergoing yet another
transformation at the hands of population geneticists, This is the singular discovery of anthropology. When
from a geographically localized gene pool or popula- E. B. Tylor (1871) separated biology or race from
tion to the small amount of difference detectable “culture,” he described it as “that complex whole which
among the most geographically separated peoples, includes knowledge, belief, art, morals, law, custom,
after overlooking the major patterns of human and any other capabilities and habits acquired by man
variation – the cultural, polymorphic, clinal, and local. as a member of society” (Tylor, 1871, p. 1) – in other
This is a new concept of race as a genetic residual, a words, as the myriad things that we key on to differen-
successor to the race as population and the race as tiate “us” from our neighbors, “them.” Today we would
essence, and it is the idea of race employed by most certainly expand the list to include the things the give
contemporary defenders of race in physical anthropo- us the earliest and most basic signals of who we are
logy and population genetics. Nevertheless, it would be and who we’re not: language, mode of dress or per-
largely unintelligible to scholars of earlier generations, sonal grooming, food preferences, body movement.
who might otherwise be inclined to agree with the This seems to be what humans evolved doing, and
proposition that race is “real.” may well precede the emergence of our species itself.
Ten Facts about Human Variation 267
In distinguishing our group from others, in these 2. HUMAN BIOLOGICAL VARIATION IS

socially transmitted, historically constructed, and sym- CONTINUOUS, NOT DISCRETE
bolically powerful ways, we structure most of our daily
lives. What makes us group members also renders all In his 1749 discussion of human variation from
of our sensory input and experience meaningful. We Natural History, General and Particular, Buffon wrote,
think and communicate using the metaphors and sym- “On close examination of the peoples who compose
bols of our group. We groom and dress ourselves each of these black races, we will find as many varieties
according to the conventions of our group; indeed, as in the white races, and we will find all the shades
the decisions we actually make during the course of from brown to black, as we have found in the white
our lives are rigidly constrained by the relatively races all the shades from brown to white” (Buffon,
meager options culturally available. In other words, 1749, p. 454).
the vast bulk of human behavioral and mental diversity That would seem, on the face of it, to preclude
is culturally constituted.1 the possibility of taxonomically dividing people
It is of some significance that the strongest cultural neatly into black and white; or even into black, brown,
distinctions are maintained between neighboring and white. Buffon’s empiricism, unfortunately, had
groups, who are nevertheless very closely related gen- already lost the day to Linnaean idealism in the area
etically to one another. This would constitute a para- of human taxonomy. Linnaeus’s rigorous hierarchical
dox if there were a close and deterministic relationship approach to biological systematics was so obviously
between genetics and human behavior. Rather, how- right in permitting us to understand the relationships
ever, if the bulk of human behavioral and cognitive among species, that it stood to reason that Linnaeus
diversity is of the sort that differentiates one group was correct in applying his ideas below the level of
from another (culture), and this variation is social the human species as well. This created a paradox
and historical in origin, then genetic variation can be in the writings of Johann Friedrich Blumenbach a
invoked to explain at best a tiny part of human differ- generation later.
ence in thought and deed – presumably some of the Blumenbach was, like Buffon, an empiricist in
differences identifiable among members of the same matters of human variation; but he was also, like Lin-
group. naeus, a taxonomist. Thus, he famously wrote in 1775,
Considered another way, an imaginary neuropep- “One variety of mankind does so sensibly pass into the
tide whose variant allele made someone a bit more other, that you cannot mark out the limits between
aggressive, say, might be found both in a wealthy them” (Bendyshe, 1865, pp. 98–99), and yet neverthe-
Parisian and in a poor Sri Lankan (and in many less proceeded to do just that. The same paradox
others). The variant allele might make its possessor inheres in the work of population geneticists over two
slightly more aggressive, but a Sri Lankan sharing the centuries later (e.g., Cavalli-Sforza et al., 1994).
allele with a Parisian would hardly have their lives An alternative to the taxonomic approach in micro-
thereby rendered significantly more similar. Their dif- evolutionary studies was suggested by Julian Huxley in
ferent lives would be shaped by their different cultural 1938 (Huxley, 1938). Since a large component of the
traditions and practices. Even the (culturally medi- variation that exists within a species is structured as
ated) responses to their aggressive behavior would geographical gradients, he suggested, why not simply
cause their personal experiences and perceptions to describe them that way, rather than trying to shoehorn
diverge. If the question, then, is to understand the the populations into taxonomic categories? In fact,
major features of human behavioral diversity, a focus Huxley did not mention humans among his examples;
on behavioral genetics is manifestly a case of the tail nor did he reject the establishment of subspecific taxa.
wagging the dog. In the 1950s other zoologists began to suggest rejecting
the subspecies altogether (Wilson and Brown, 1953),
and Livingstone (1962) was extending the argument to
1
Biologized theories of human history have been put forward humans when he denied the very biological existence
periodically from Arthur de Gobineau’s (1853–1855) The of human races.
Inequality of Human Races through C. D. Darlington’s (1969) Trying to explain clinal variation in human phys-
The Evolution of Man and Society. It is in this narrow historical
sense, where (as Émile Durkheim famously noted) social facts ical form from northern to southern Europe in taxo-
are only explicable by prior social facts, that the analytic separ- nomic terms is what compelled William Z. Ripley
ation between biological (microevolutionary) and cultural phe- (1899) to introduce a subdivision of “the races of
nomena has been most useful. In a broader sense, the
interaction between the “natural” and the “cultural” is more Europe” into Teutonic (Nordic), Alpine, and Mediterra-
complex and problematic. At very least, historical events often nean. (Today, even the simple use of a plural in his title
have biological consequences, which in turn engender different seems foreign to us.) Carleton Coon’s (1939) revision of
responses – as evidenced in the well-known relationships among
agriculture, malaria, the human gene pool, and modern The Races of Europe identified over a dozen of them.
medicine. Where no criteria exist other than “difference,”
268 Jonathan Marks
certainly a broad cline of physical form could be Further, the relationship between processes of
subdivided in a pseudo-taxonomic fashion effectively human demographic history, and the products they
without limit. It is simply a classic square-peg/round- have yielded at different times, is often far from clear.
hole problem. Patterns of relative genetic distinctiveness might be
This clinal pattern is evident for most human traits, expected from several different demographic pro-
extending from lactose persistence through to skin cesses. Consequently, different clustering analyses
color. The reason for this pattern is two-fold: (1) nat- applied to human populations by different researchers
ural selection, with environmental conditions varying have often yielded different results. Clusters of popula-
gradually over space; and (2) gene flow, culturally tions may be produced as well simply by sampling
mediated in humans. There are very few systems that discontinuously (Serre and Pääbo, 2004).
do not show much in the way of geographical gradi- The idea that human populations fall naturally
ents. Yet even the genetic markers that permit full into genealogical clusters is itself the result of a gloss
differentiation of disparate groups (almost all one on the Biblical theory of human biogeography. Gen-
allele in West Africans and almost all another allele in esis 10 tells us that Noah’s three sons (Ham, Shem,
East Asia at the Duffy blood group locus on chromo- and Japheth) went out and populated the world after
some 2 exhibit clines of differing intensities in different surviving the Deluge. Ham has sons named Cush,
regions (East Africa, West and South Asia). Mizraim, Phut, and Canaan – and is the ancestor
It seems, then, that a division of the world into of both the Babylonians (Babel) and the Egyptians
human races – reasonably discrete from one another (Mizraim). Shem has sons named Elam, Asshur,
and relatively few in number – was an aberration, Arphaxad, Lud, and Aram – and is an ancestor of
derived from a peculiar view of human variation other local city-states. And Japheth sires Gomer,
adopted by scientists from the seventeenth to the twen- Magog, Madai, Javan, Tubal, Meshech, and Tiras –
tieth century. Scholars have differentiated the peoples and once again, is an ancestor of a group of city-
they encounter according to diverse criteria, but states. “These are the families of the sons of Noah,”
human variation in nearly all times and places has the Bible tells us, “after their generations, in their
been perceived on a local, not a continental/global, nations: and by these were the nations divided in the
scale. This is because fundamental patterns of human earth after the flood.”
difference are principally gradational, not discrete. By the first century, the Jews understood this to
explain the peopling of the three known continents.
According to The Antiquities of the Jews by Flavius
3. CLUSTERING POPULATIONS Josephus (Book I, Chapter 6), Ham heads south to
IS ARBITRARY beget the Egyptians, Ethiopians, and other Africans;
Shem begets the Asians as far east as India (including
Human identities are culturally produced, and can the Hebrews themselves, through his son Heber); and
assume a wide range of forms. Those that are princi- Japheth is the ancestor of the European peoples, as far
pally geographic can be extensively subdivided; one west as Spain.
can be Caucasian, Nordic, Slavic, Baltic, and Latvian In the nineteenth century, this story was embel-
simultaneously. All have been racialized by someone or lished even further, as Noah curses his grandson
another. Canaan for an ambiguous sexual deed perpetrated
Approaching the issue from the bottom, so to by his father Ham. Josephus had interpreted the
speak, where the most basic human populations are curse in the context of Jewish origins, and the polit-
local, how do they fit together into more inclusive ical/religious/military transformation of “Canaan”
entities? into “Judea.” But to American physical anthropolo-
We could try to cluster them genealogically, but as gists in the era of slavery, that curse became the
Frederick Hulse (1962) pointed out, there is no reason Biblical justification for the modern enslavement of
to think human populations are actually genealogically Africans.
structured entities, and every reason to think they are Nevertheless, there was very little change in the
not. Gene flow (both small-scale and long-term, and biohistorical model explaining the human race. The
large-scale and short-term) is a pervasive feature of three sons of Noah emigrate to the corners of the earth
human history, and the horizontal modes of genetic and populate it, becoming the pure progenitors of the
transmission it produces are complementary to the people living there; and where their remote descend-
vertical modes of genetic transmission depicted in ants encounter one another, impure races are found.
genealogical trees (Fix, 2005). Consequently, the more The power of this model is such that it even underlies
accurate mode of representation of human populations some genetic studies of the modern era. Thus, promin-
is not as a tree, but as a trellis, capillary system, or ent population geneticists can casually write, as
rhizome (Moore, 1994; Palsson, 2007; Arnold, 2009). recently as 1993:
[H]uman populations can be subdivided into five major estimated to be an admixture of 65% ancestral Chinese
groups: (A) negroid (Africans), (B) Caucasoid (Europeans and 35% ancestral Africans” (Bowcock et al., 1991,
and their related populations), (C) mongoloid (East Asians p. 839). That is, the samples were intended to represent
and Pacific Islanders), (D) Amerindian (including Eskimos), larger categories assumed to be natural and separate.
and (E) australoid (Australians and Papuans). (There are
intermediate populations, which are apparently products of
gene admixture of these major groups, but they are ignored
here.) (Nei and Rouchoudhury, 1993, pp. 936–937)
5. POPULATIONS ALSO HAVE
A CONSTRUCTED COMPONENT
Of course, there was never a time when people lived
only in Lagos, Oslo, and Seoul; indeed, the most “Population” is a term that is notoriously difficult
ancient representatives of Homo sapiens sapiens are to define rigorously. The usage above is intended to
right there in the middle. That raises a crucial question juxtapose the “local” against the “global” – or onto-
about the statistical clustering of populations: What do logically real “demes” against reified human mega-
the clusters actually represent? What is their connec- populations. And yet, local human populations, as
tion to human history? While most population geneti- previously noted, tend to distinguish themselves by
cists readily acknowledge that the clusters are features such as language, dress, religion, and dietary
statistical reifications (Templeton, 1998), it is not too prohibitions or preferences. These are not biological
difficult to find them naı̈vely interpreted as cladoge- attributes, but they help circumscribe an entity that is
netic events, with that occasional rare admixture. to some extent biological, namely the local human
And indeed, philosopher Robin Andreasen (2000, population or deme.
2004) misunderstands the evolutionary meanings of The boundaries being nonbiological, they are con-
those trees in precisely that fashion, as a series of sequently porous to biological input, in the form of
literal, historical bifurcations that produced – you gene flow (e.g., Hunley and Long, 2005). This can take
guessed it – races. place through social practices, such as exogamy and
adoption; economic practices, such as trade and sub-
sistence; and political practices, such as warfare, slave
4. POPULATIONS ARE BIOLOGICALLY raids, and forced migrations.
REAL, NOT RACES Unfortunately, a large class of population genetics
models have tended to work best for populations in
Gilmour and Gregor (1939) coined the word “deme” to isolation from one another, which in turn necessitates
refer to the local population that exists as an ecological a high degree of “purity” for the populations under
and social unit in nature. The focus on the population study. This assumption was raised during the public
genetics of human demes is what permitted biological discussion over the Human Genome Diversity Project
anthropologists of the 1970s to avoid “race” altogether. in the 1990s, as the Project itself continually talked
The application of this concept to human diversity of “isolated” populations. But this had in fact been
revolutionized the study of physical anthropology in highlighted as a problem half-a-century earlier, as
the years following World War II. The genetical pro- Boston University’s anthropological geneticist William
cesses described in the evolutionary synthesis were C. Boyd had proclaimed the purity of the Navajo group
measurable and meaningful at the local level; Sewall he was studying. But cultural anthropologist Clyde
Wright’s work showed that local populations were Kluckhohn knew the specific community and its eth-
effectively the units of general microevolution. That is nohistory, and knew of its extensive interbreeding,
consequently where the study of human population with Walapai, Apache, Laguna, and Anglo/Spanish
genetics would have to focus. contributions. “In spite of all this, [they] conclude from
Larger units than the deme lack cohesion or time their blood group data that the Ramah Navaho repre-
depth. Their evolutionary meaning is consequently not sent an ‘unusually pure’ Indian group” (Kluckhohn and
obvious. To adopt a unit of analysis of human biology Griffith, 1950, p. 401). The implication was clear that
larger than that of the local population or deme, then, the population in question would actually have their
is what requires some justification today. Perhaps the complex history erased by the geneticists, and would
most interesting question in this vein is that of repre- be falsely simplified and reified into one in which they
sentation: Can local populations “stand for” anything were more-or-less “pure.”
other than themselves? In one famous study, geneti- The myth that non-European peoples are “pure”
cists used 94 African pygmies, 64 “Chinese . . . living in and “unmixed,” and have more or less always been
the San Francisco Bay Area,” 110 samples from “indi- where (and as) we find them today, was comprehen-
viduals of European origin from ongoing studies in sively refuted by Eric Wolf (1982) in Europe and the
our laboratories or reported in the literature,” and People without History. That it complicates some popu-
concluded sweepingly that “ancestral Europeans are lation genetic analyses is unfortunate (Moore, 1994;
270 Jonathan Marks
Templeton, 1998), but human populations are biocul- structured quite differently from the rest of the known
tural units, connected economically, socially, and gen- human gene pool.
etically; and with complex histories intertwined with
those of their neighbors (Lasker and Crews, 1996).
7. PEOPLE ARE SIMILAR TO THOSE NEARBY
AND DIFFERENT FROM THOSE FAR AWAY
6. THERE IS MUCH MORE VARIATION
WITHIN GROUPS (POLYMORPHISM) The primary factor governing between-group variation
THAN BETWEEN GROUPS (POLYTYPY) in our species is geography, a fact known even to the
ancients. This allows us grossly to predict patterns of
Lewontin’s (1972) calculation that there is six times relatedness: a Dane will tend be more similar to an
more within-group variation than between-group vari- Italian than to a Hopi. This, however, only allows us
ation in the gene pool of Homo sapiens has been the to classify the Dane and the Italian in relation to the
subject of periodic criticism, but the results have Hopi; it does not tell us whether Danes and Italians
proved remarkably robust to the kinds of genetic data themselves belong to the same group or to different
analyzed. Barbujani et al. (1997) found a similar result ones. There are indeed geographical patterns in the
for nuclear DNA, as did Rosenberg et al. (2002). human gene pool, and they can indeed be used to allot
The most obvious conclusion is that the human people into groups (Witherspoon et al., 2007); the
species does not come naturally partitioned into groups simply do not correspond to “races,” in any
reasonably discrete gene pools, which had been the previously or generally understood sense of that term.
predominant theory of race for most of the twentieth The ability to discriminate Swedes from Nigerians gen-
century. etically does not tell you what to do with Moroccans.
A. W. F. Edwards (2003) has recently criticized the The existence of genetic variation over space is thus
invocation of these numbers against the race concept disconnected from race as theory of human groups and
as “Lewontin’s fallacy,” on the grounds that a propor- their classification – a point sufficiently important, yet
tion of the diversity detectable in the human gene pool subtle, as to be lost on some geneticists! In fact, one
is indeed correlated with geography, and thus can be needs neither statistics nor genetics to tell an Inca from
used to sort people into large groups, if one focuses a Dinka.
upon it closely enough. The argument here is not with In general, the most geographically proximate
the data, but with the meaning of the data and its peoples are the most genetically similar. In rare cases,
relation to human races. Geographical correlations a (permeable) barrier of language, politics, or ethnicity
are far weaker hypotheses than genetically discrete might serve to reinforce a genetic distinction between
races, and they obviously exist in the human species one people and their neighbors (Hulse, 1957); these
(whether studied somatically or genetically). What is differences are nevertheless often genetically subtle,
unclear is what this has to do with “race” as that term arbitrary, and discordant. If the Ainu of Hokkaido are
has been used through much of the twentieth century – more hirsute than other Japanese, can one be a glab-
the mere fact that we can find groups to be different rous Ainu? Likewise, can one be an Rhþ Basque, or a
and can reliably allot people to them is trivial. Again, tall pygmy?
the point of the theory of race was to discover large The answer is presumably “yes” to all of those,
clusters of people that are principally homogeneous although perhaps with varying degrees of aspersion
within, and heterogeneous between, contrasting cast upon one’s ancestry, in proportion to the degree
groups. Lewontin’s analysis shows that such groups of purity ascribed to the group itself. Once again, how-
do not exist in the human species, and Edwards’s ever, this is hardly meaningful in the context of races;
critique does not contradict that interpretation. but rather, only in the context of local populations.
Moreover, the Lewontin numbers show that pat- Perhaps the most celebrated confusion of geo-
terns of human genetic diversity simply do not map graphic difference for race followed the publication of
well onto the patterns of human behavioral or cogni- Genetic Structure of Human Populations (Rosenberg
tive diversity. The latter kinds of differences tend to be et al., 2002). The authors studied genetic variation
localized at the borders of human groups, as noted in 1052 people from 52 populations and then asked a
above, and are of the sort we call cultural (Peregrine computer program called Structure to group the
et al., 2003; Bell et al., 2009). To the extent that genetic samples. When they asked it to produce two groups,
diversity is structured quite differently (mostly poly- Structure gave them EurAfrica and East Asia–
morphism and clines), it seems unlikely that genetic Oceania–America. When asked for three groups, Struc-
differences could play a significant role in understand- ture gave Europe, Africa, and East Asia–Oceania–
ing the major patterns of human behavior, unless America. When asked for four, it gave Europe, Africa,
variation in the hypothetical genes involved were East Asia–Oceania, and America. When asked for five,
it gave roughly the continents. And when asked for 8. RACIAL CLASSIFICATION IS HISTORICAL AND
six, it gave the continents and the Kalash people of POLITICAL, AND DOES NOT REFLECT NATURAL
Pakistan. When asked for more (up to twenty groups), BIOLOGICAL PATTERNS
it gave more (Bolnick, 2008).
This was more or less what population geneticists The contemporary racialization of Hispanics in the
had been doing with the human gene pool since the United States (see above) is certainly prima facia
pioneering work of Cavalli-Sforza and Edwards (1965). evidence for the political embeddedness of racial
On the face of it, once again, this would seem to have classifications. In classic anthropological fashion,
little relevance for race. The user specifies the number the cultural aspects of race are revealed most clearly
of groups, and geographic proximity is the strongest when we contrast the classifications and their uses
predictor of similarity, so asking the computer to break from place to place and time to time. Thus, while
the human species into five groups might reasonably “Black” in the United States has effectively meant
be expected to yield groups roughly corresponding “possessing any recent African ancestry,” that
to the continents. And the Kalash people of Pakistan category in the United Kingdom traditionally
certainly do not have green skin and square heads; referred to South Asian ancestry (meaningful in the
nor do they constitute a “natural” contrast against context of the colonial relationships between Britain
Europeans or Africans. and India), and only recently has the category
Nevertheless, a headline in the New York Times “Afro-Caribbean” emerged there to designate what
announced, “Gene study identifies five main human Americans mean by “Black.” People of South Asian
populations, linking them to geography” and quoted ancestry in the United Kingdom are now commonly
Marcus Feldman2, the principal author of the study, regarded as “Asian” in the United Kingdom, but in
to the effect that “the finding essentially confirmed the the United States the term instead tends to connote
popular conception of race” (Wade, 2002). people of East Asian ancestry.
Of course the popular conception of race as a clas- Central and South American classifications have
sification system applies not just to the more-or-less tended to incorporate more categories, based on actual
indigenous peoples surveyed by the geneticists, but as variation in skin shade, in contrast to the “one drop of
well to the entire admixed urban populations of the blood” rule prevalent in the United States. While there
modern world, especially the Americas. This raises an is commonly status differential associated with skin
important criticism of genetic “racial” studies: their color, it is nevertheless quite different from the binary
focus on a mythological past rather than on a real racial system of the United States.
present (Cartmill, 1998). What biological relevance The point is that biological or genetic difference
does an exercise like this have, after all, for the peoples can be studied and quantified, but it is not race. Race
of New York, Chicago, Los Angeles, Mexico City, Rio de is a sense-making system imposed upon the facts of
Janeiro, or Johannesburg? It is indeed an odd and difference. Races are not merely human divisions, they
perverse approach to history, geography, and genetics are politically salient human divisions. All classifica-
that would cast a blind eye to the centuries of colonial tions exist to serve a purpose; the purpose of a racial
contact and demographic reconfiguration that have classification is to naturalize human differences – that
constructed the human gene pool. is, to establish important categories and make their
In modern American populations, it is certainly distinctions appear to be rooted in nature, rather than
reasonable to expect people who look “black” to tend in history or politics.
to cluster genetically with Africans when examined The pervasive tendency for racial classifications to
with carefully selected genetic markers (Bamshad see sub-Saharan Africans as a single group, for
et al., 2003), but the vagaries of Mendelian genetics example, has far more to do with the politics and
and the complexities of human history will combine history of slavery than with the gene pool of Africans.
to place an increasing amount of weight on the phrase After all, fieldworkers like Seligman (1930) and
“tend to.” Further, given nontrivial amounts of poly- Hiernaux (1975) consistently emphasized the physical
morphism and admixture, there is always a nontrivial diversity of Africans. Julian Huxley could write, “It is a
possibility that a particular person may have the commonplace of anthropology that many single terri-
“wrong” racial marker at a specific locus. That is ultim- tories of tropical Africa, such as Nigeria or Kenya,
ately why a racialized pharmacopoeia is a very poor contain a much greater diversity of racial type than
and risky substitute for an individualized one, which all Europe” (Huxley, 1931, p. 379). Today, their genetic
will have to be predicated on the direct assessment of diversity is generally considered to harbor the ances-
individual genotypes. tral gene pool of the rest of the world. Sub-Saharan
Africans thus encompass more genetic diversity
than other “races,” and more significantly, constitute
2
Feldman (personal communication) said it was a misquotation. a paraphyletic category, and are thus not even
272 Jonathan Marks
taxonomically comparable to other “races” (Marks, Thus, the temptation to represent evolutionary
1995). So if the empirical data have long been known history as a series of cladogenetic events seems to be
to contradict it, how then do we account for the pre- nearly as problematic just above the human species as
sentation of sub-Saharan Africans as consistently just below it. Clearly, the demographic histories of
monolithic in racial classifications as late as those of these populations made the patterns of genetic differ-
Campbell (1962) and Boyd (1963)? 3 ence we see today more difficult to interpret than
earlier generations of scholars appreciated.
9. HUMANS HAVE LITTLE GENETIC

VARIATION
10. RACIAL ISSUES ARE SOCIAL–POLITICAL–
ECONOMIC, NOT BIOLOGICAL
Ferris et al. (1981) found a much greater degree of
heterogeneity in the mitochondrial DNA of chimpan-
The most important aspect of the study of race is its
zees and gorillas than in humans. This finding was
connection to racism, a political ideology in which
soon extended to nuclear DNA by Deinard (1997) and
humans are ranked according to group membership.
Kaessmann et al. (2001). Stone et al. (2002) found very
It has occasionally been argued that the absence of
different patterns of diversity in chimpanzees and
taxa equivalent to zoological subspecies in humans
humans as well, chimpanzees having deeper coales-
invalidates racism, as if all we had do to disband the
cences, and more between-group variation (which is
Ku Klux Klan would be to teach them some population
especially striking, given their considerably more
genetics.
restricted range), than humans. At some loci where
This view, however, misrepresents the basis of
humans are variable, apes turn out to be less variable,
racism, for it takes racism to be predicated on science.
but this is the result of a statistical bias – if we try to
In fact racism is independent of science, and is simply
identify variation in apes where humans are already
one of many anti-democratic political discourses that
known to vary, then we miss the many loci at which
function to rationalize social inequalities. Sexism, anti-
apes vary but humans do not.
Semitism, and homophobia are quite real, in spite of
Although it must be noted that there is a
the fact that the groups constituted by women, Jews,
conservation-driven push towards “taxonomic infla-
and homosexuals possess varying degrees of “natural-
tion” in the apes, the levels and degrees of genetic
ness.” In other words, it is the social ranking and
differentiation in our closest relatives seem to be
prejudice, not the biology, which comprise the salient
considerably different from our own. Ape subspecies
features of racism.
appear to cluster strongly together with mitochondrial
Race is thus paradoxically of minor relevance to
DNA, for example, while human races do not. To the
racism. The “race” in “racism” is the first – the essen-
extent that they have traditionally been divided into
tialist – version of race, in which any group can possess
subspecies, then, these great ape taxa represent very
its own innate qualities, and individual people can be
different entities than human races.
relied upon to embody those qualities. The categories
One interesting consequence of finding such high
are still real and experienced, however, despite how
levels of genetic diversity in the apes is the difficulty it
little they may correspond to biology (Smedley and
imposes upon phylogenetic reconstruction (Ruano
Smedley, 2005).
et al., 1992; O’hUigin et al., 2002). Very high levels of
If “white” and “black” denote intractably large,
homoplasy and ancestral polymorphism undermine
highly heterogeneous, extensively overlapping popula-
the assumption of parsimony in molecular phyloge-
tions, then, as Lewontin (1972) recognized, there can
netics (Marks, 1994; Satta et al., 2000; Chen and Li,
be little justification for ascribing great biological
2001), and contribute to the relatively large statistical
meaning to the perceived discontinuities between
errors associated with the calculation of divergence
them. On the other hand, if: (1) considerable social
times of human and ape species (Stauffer et al., 2001;
inequality is mapped onto the categories; and (2)
Glazko and Nei, 2003; Kumar et al., 2005). This in turn
phenotypes are coconstructions of genotypes and the
suggests the need for models of ape-human ancestry
cultural conditions under which the genotypes are
more complex than just a sequence of simple bifurcations
expressed, then it follows that; (3) significant perceived
(Chaline et al., 1991; Deinard, 1997; Barbulescu et al.,
differences between the two groups, particularly etio-
2001; Marks, 2002; Patterson et al., 2006; Arnold, 2009).
logically complex ones like odor (Classen, 1995), body
form (Bogin, 1988), or intelligence (Lewontin et al.,
3
Coon’s (1962) The Origin of Races followed Gates’ (1948) 1984), are simply more likely to be attributable to their
Human Ancestry in splitting the Khoisan peoples of southern
Africa off from other Africans, thus doubling the number of
different social statuses (especially class and ethnicity)
African races. than to their gene pools.
This conclusion, obviously, is not value-neutral. difference is consequently often quite valuable. After
The ascription of inequality to biological causes is a all, the newest work is hardly carried out in an intellec-
political position that minimizes the role of political– tual, historical, or cultural vacuum.
economic factors in producing and maintaining that Earnest Hooton almost understood this, trying to
social inequality. The implication is that biological differentiate his own ostensibly benign physical
causes require biological remedies, or at least, not anthropology from that of the Nazis, while neverthe-
remedies involving significant expenditures on social less remaining a eugenicist long after it fell out of
programs. Obviously there is considerable harmony fashion in American academia. He warned, somewhat
between this ostensibly scientific conclusion and a pol- poignantly,
itical agenda of social conservatism, often explicitly so.
There is a rapidly growing aspect of physical anthropology
Indeed, this is what links the reasoning of the social
which is nothing less than a malignancy. Unless it is excised,
Darwinists, eugenicists, and segregationists of earlier it will destroy the science. I refer to the perversion of racial
eras with works like The Bell Curve (Herrnstein and studies and of the investigation of human heredity to political
Murray, 1994) in the modern era. Consequently they uses and to class advantage . . . [T]he output of physical
necessitate a higher degree of scrutiny than the ordin- anthropology may become so suspect that it is impossible to
ary run of scientific work, and generally, they do not accept the results of research without looking behind them for
stand up well to it (Boas, 1911; Hogben, 1931; Merton a political motive (Hooton, 1937, pp. 217–218).
and Montagu, 1940; Dobzhansky, 1962, 1963; Gould,
1981; Lieberman, 2001; Marks, 2005).
In the case of health care, for example, it is quite
uncontroversial that identifiers such as ancestry, age, CONCLUSIONS
and occupation carry different statistical health risks
and that knowledge of them can aid in producing Both human beings, and the scientific study of human
a proper diagnosis. Being born white carries a risk of beings, are coproductions of nature and culture.
1 in 2 500 of having cystic fibrosis; being born black Human biologists are very familiar with the manifold
carries a risk of 1 in 15 000. Nevertheless, one needs to processes by which “culture” is inscribed upon the
guard carefully against misdiagnosing the presentation human organism, and is ultimately not separable
of symptoms in a black child, say, on the grounds that from the biology, or the human phenotype – “nature.”
cystic fibrosis is a white child’s disease, since that act It has proven more difficult to accept the idea that
puts lives directly at risk (Garcia, 2003). Further, race science itself – despite being a human activity, taking
itself is a red herring here: being Ashkenazi Jewish, place in a cultural context, and being subject to con-
Pennsylvania Amish, “not northern European,” a foot- flicting interests of various kinds – produces conclu-
ball player, a primary school teacher, or a computer sions about nature that are ultimately also not
hacker puts one at higher risk for familial dysautono- separable from culture. The idea that you can separate
mia, Ellis–van Creveld syndrome, lactose intolerance, the natural from the cultural with a high degree
knee problems, mild viral infections, and carpal tunnel of confidence, however, is an Aristotelian survival
syndrome, respectively, but those labels do not desig- (Goodman et al., 2003).
nate groups we would identify as races. And more The most significant aspect of the study of human
importantly, since the social inequality associated with diversity is that it consists of natural–cultural facts.
race is a significant variable affecting many aspects of These facts emanate from the kinds of questions
life and health care (Sankar et al., 2004), it should not framed, the manner in which categories are envisioned
be surprising the some of the most well-known racia- and established, the applications that assign people to
lized medical issues – low birthweight and hyperten- the categories, the meanings attributed to group mem-
sion – also do not stand up well under scrutiny as bership, and of course, the program of the investigator.
innate differences (David and Collins, 1997; Kaufman Certainly there is a base of data that can inform us
and Hall, 2003). about the patterns of diversity that exist in our species,
Most significantly, the modern context of racial both somatic and genetic. The problem lies in the pre-
science involves another player, in addition to science sumptions: (1) that the biological data on human vari-
and politics – the economics of health care, in which ation are fundamentally separable from their cultural
“racial pharmacogenomics” is being positioned as a context and values, and from the interests of the scien-
source of new markets for the pharmaceutical industry tists producing them; and (2) that the data themselves
(Duster, 2005; Bibbins-Domingo and Fernandez, are meaningful independently of a stream of Euro-
2007). With such conflicting interests, it becomes American ideas about difference, heredity, and hier-
harder than ever to evaluate the merits of scientific archy. That is why the problem of race has never been
research on the genetics of race. A broad perspective resolved by genetics; its domain is anthropological,
on what we already know about science and human rather than biological.
274 Jonathan Marks
DISCUSSION POINTS Boyd, W. C. (1963). Genetics and the human race. Science,
140, 1057–1065.
1. What are the incompatibilities among the three Brodkin, K. (1999). How Jews Became White Folks and What
concepts of race discussed in this essay? That Says About Race in America. Piscataway, NJ: Rutgers
2. Why can’t we separate facts of nature from culture? University Press.
Buffon, Comte de (1749) Variétés dans l’espèce humaine. In
3. Are Hispanics a race?
Histoire Naturelle, Générale et Particuliére, Vol. 3. Paris:
4. Old anthropology books used to show maps of the
L’Imprimerie Royale, pp. 371–530.
races of the world, with, for example, no presence
Campbell, B. (1962). The systematics of man. Nature, 194,
of Europeans, Asians, or Africans in America. What 225–232.
are the merits of, and problems with, that? Cartmill, M. (1998). The status of the race concept in phys-
5. What are the major patterns of human genetic vari- ical anthropology. American Anthropologist, 100, 651–660.
ation and the major patterns of human cognitive Cavalli-Sforza, L. L. (1974). The genetics of human popula-
variation, and how do they relate to one another? tions. Scientific American, 231, 81–89.
What implications can be drawn from that? Cavalli-Sforza, L. L. and Edwards, A. W. F. (1965). Analysis
of human evolution. In: Genetics Today: Proceedings of the
XI International Congress of Genetics, S. J. Geerts (eds).
Oxford: Pergamon, pp. 923–933.
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16 The Evolution and Endocrinology
of Human Behavior: a Focus on Sex
Differences and Reproduction
Peter B. Gray
INTRODUCTION BACKGROUND
Overarching theoretical frameworks

The aim of this chapter is to highlight some of the core
concepts and empirical findings concerning the evolu- There is more than one way to answer a “why” question
tion and endocrinology of human behavior. To do this, in biology (such as why do sex differences exist).
we first review some basic principles in the evolution In fact, we can distinguish four complementary
and endocrinology of behavior. These principles have approaches to answering any biological question:
been derived from studies with various taxa rather (1) proximate (mechanism); (2) adaptation (function);
than humans alone. Indeed, nonhuman theoretical (3) phylogenetic (evolutionary history); and (4) devel-
and empirical findings have inspired some of the opment (ontogeny) (Tinbergen, 1963; Bolhuis and
human research, and the research on humans should Giraldeau, 2005). A focus on the evolution and endo-
be viewed in comparative contexts. Next, we investi- crinology of human behavior most clearly integrates
gate a series of examples illustrating empirical two of these approaches – endocrine mechanisms of
research on the evolution and endocrinology of human behavior within a functional perspective – but may also
behavior with a focus on sex differences and repro- consider the ontogeny of behavioral endocrine mech-
ductive behavior. These examples have been chosen anisms and phylogenetic context.
because they illustrate well the relationships between Adoption of a functional, or adaptive, perspective
human hormones and behavior and they offer enough has several advantages. For one, it stimulates the devel-
data to enable drawing some conclusions. For some opment of testable hypotheses. For example, suppose
of these examples, cross-cultural data are also avail- one recognizes that human males face a life history
able, helping show the ways endocrine mechanisms allocation problem of optimizing investment in mating
underlie human behavior across variable sociocultural (male–male competition and mate seeking) and
environments. parenting effort. One then wonders about the neuroen-
A comprehensive literature review of human find- docrine mechanisms that modulate this allocation
ings, much less nonhuman behavioral endocrinology, challenge. Another advantage is that an adaptive per-
would involve a very long book rather than a book spective helps organize what might otherwise be a pile
chapter. Yet in the course of reviewing some well- of facts about endocrinology and behavior; it suggests
documented examples, readers may gain an appreci- some underlying organizational principles for why
ation for the excitement of this research niche as mechanisms work the way the do (e.g., why male–male
well as the types of research questions remaining competition and mate seeking are both commonly
to be addressed. For the unavoidably hooked student linked to elevations in male testosterone – both beha-
or researcher, please see Ellison and Gray (2009), viors facilitate reproductive access to mates).
Carter et al. (2005) Adkins-Regan (2005), Nelson Adoption of a focus on the proximate, or mechan-
(2005), Sapolsky (2004), Becker et al. (2002), and Pfaff istic, understanding of behavior may have several
et al. (2002) for excellent overviews of hormones and different advantages (Panksepp et al., 2002; Piersma
behavior. In these latter volumes, readers can find and Drent, 2003). For one, an understanding of mech-
full treatments of topics such as the relationships anism helps constrain adaptationist thinking. Neuro-
between hormones and diet, sleep, exercise, aggres- endocrine mechanisms underlying behavior tend to
sion, and stress that are largely outside the scope of evolve through “tinkering” of existing mechanisms
the present chapter. (e.g., alterations in neurotransmitter or hormone
277
278 Peter B. Gray
receptor distribution; changes in neural connections), Evolution of human behavior

casting doubt on novel, modular mechanisms of Evolutionary theory recognizes that selection can act
human behavior arising de novo during recent human on multiple levels (gene, individual, group) but that
evolution (Quartz and Sejnowski, 2002). Another selection on individuals tends to be the most powerful.
advantage of focusing on mechanisms is that they sug- Consequently, adaptive accounts of human behavior
gest, based on principles of homology, mechanisms of typically consider the fitness (relative reproductive
behavior that may operate in humans (like in other success) costs and benefits to individual behavior.
species). In turn, this can yield predictions about The overarching question from this adaptationist
the neuroendocrine bases of human behavior based approach is: how do individuals behave in ways maxi-
on findings from nonhuman animals. For example, if mizing reproductive success?
research on rodents implicates the hormone oxytocin In maximizing reproductive success, behaviors can
in pair bonding, then this knowledge may stimulate arise that benefit others like kin at cost to oneself.
research in humans investigating the role of this same Kin selection theory shows how heritable tendencies
hormone in human pair bonding. A further benefit to benefit relatives can spread. Co-operative behavior
of studying mechanisms in a comparative approach among unrelated individuals can also evolve in various
is that the types of invasive, experimental designs ways, including via processes of reciprocal altruism
conducted in, say, laboratory rodents are often not (I scratch your back now and you scratch my back
ethically or logistically feasible in humans, meaning later) or indirect reciprocity (I behave in ways leading
that we are forced, to some degree, to rely on evidence to you wanting to co-operate with me). Fitness costs to
from other species for making causal inferences on behavior are also contingent on a variety of variables:
hormone-behavior relationships. The nonhuman work reproductive value (likelihood of future reproductive
may converge with clinical findings from atypical output), social status, and physical condition of both
human development (e.g., behavioral effects of a actors and recipients of behavior impact whether selec-
mutated hormone receptor or enzyme such as 5-a tion will favor certain behaviors.
reductase). Though largely outside the scope of this How individuals maximize reproductive success
chapter, another important aspect of mechanisms is will depend on the social context. Hence, historical
that an understanding of them may have implications and cross-cultural variation in human sociocultural
for the development of clinical treatments for beha- environments is important (Low, 2000; Richerson and
vioral problems (e.g., use of hormone replacement Boyd, 2005). This sociocultural variation presents
therapy for treating depression or sexual problems). different opportunities and constraints to individuals:
In this chapter, I highlight the interplay between with kin to assist with allocare, a woman may have
functional and mechanistic approaches to human more children; in small-scale bellicose societies in
behavior. In sections below, brief summaries of the which male–male bonds enable defense against neigh-
relevant concepts are provided. It also bears emphasis bors, weaker husband–wife and father–child relation-
that any behavior has a developmental course to it ships may emerge; when formal education systems
(e.g., the onset of sex-differentiated behavior), even if arise, children may reduce their care of younger sib-
less emphasis is given to development in this chapter. lings to advance their own education.
Moreover, phylogeny may have important impli- Several additional complications remain. A school
cations, especially when considering whether mechan- of thought, championed by evolutionary psycholo-
isms of human behavior may operate similarly or gists, questions whether humans would be expected
differently compared with other species. The most to behave adaptively in contemporary environments
straightforward approach is to assume that mechan- (Barkow et al., 1992; Irons, 1998). The psychological
isms of human behavior may be similar to those of mechanisms underlying human behavior evolved in dif-
other taxa, especially the more closely related to us ferent environments from those in which we typically
(e.g., rhesus monkeys more relevant than rats, in turn find ourselves (like a large city populated by strangers).
more relevant than fruit flies or nematodes). However, Thus, we may behave maladaptively in our novel
interesting exceptions to homologous mechanisms worlds, yet understandably according to scenarios of
exist and should be appreciated; for example the human evolution. Other reasons for humans behaving
masculinizing effects of hormones in rodent brains in nonoptimal ways include pleiotropic effects, trade-
appear, unlike in primates, to entail the conversion of offs, and constraints. As an illustration, testosterone
testosterone to estradiol (which does the masculini- has multiple effects (pleiotropy), some of which may
zing!) (Nelson, 2005). Also showing the importance of work against one another (e.g., a trade-off between
phylogeny, effects of hormonal changes across the maintaining elevated testosterone levels in response to
menstrual cycle are much more pronounced in rodents social challenges that may compromise immune func-
and New World monkeys than in Old World monkeys tion). For review of these general principles concerning
and apes (Dixson, 1998). the evolution of human behavior, a number of clear
The Evolution and Endocrinology of Human Behavior 279
accounts exist (Betzig, 1997; Pinker, 1997; Hrdy, 1999; to steroid release by the gonads. These feedback loops
Cartwright, 2000; Barrett et al., 2002; Konner, 2002; are usually negative, but occasionally positive. More-
Buss, 2003, 2005; Gaulin and McBurney, 2004). over, they incorporate information from other struc-
Some implications from evolutionary principles tures and systems too; intricate co-ordination with the
of human behavior can be drawn with respect to the nervous system, immune system, and other endocrine
underlying endocrine mechanisms. One implication is axes allows behavioral responses appropriate for an
that males and females have faced different selective individual’s physical condition and social context.
environments over evolutionary history, and thus we The causal arrow between hormones and behavior
might expect to find endocrine mechanisms playing an points both directions. Elevations or decreases in hor-
important role in the development of sex differences. mones may alter behavior; you may have noticed this
Human reproduction typically occurs within contexts if you have a neutered or spayed pet since these oper-
of long-term pair bonds; consequently, we should ask ations have altered sex steroid secretions. Behavior can
about mechanisms underlying pair bonds and parental also affect hormones. If you have felt an acute rise in
care in nonhuman animals to gain potential insights arousal when giving a presentation to a large audience,
into these human behaviors. Kinship has occupied a it is quite possible that this behavior increased your
central role in our ancestral social organization, even if cortisol levels. The bidirectional causal effects of
it sometimes seems less important in large cities hormones and behavior reflect the complex feedback
replete with strangers and friends rather than extended loops through which these systems operate.
family members. We might expect that degree of In this chapter, I will focus on a limited set of
relatedness between individuals (or proxies thereof, hormones. The hypothalamus-pituitary-gonadal axis
such as proximity during early childhood develop- alluded to above will feature in discussions of human
ment) will have predictable impacts on endocrine- sex differences and sex-typed behavior. Prolactin is a
mediated behavior. Finally, we must locate the peptide hormone released, largely under negative
development and expression of behavior, and under- control by dopamine, from the anterior pituitary gland.
lying mechanisms, in particular sociocultural contexts. Oxytocin and vasopressin are small peptide hormones
The specific environment in which behavior develops released from the posterior pituitary. Each of these
and is expressed will shape how mechanisms work hormones passes through the circulatory system until
(see Chapter 24 of this volume). reaching target tissues where they are bound by the
appropriate hormone receptor (e.g., the androgen
receptor binds testosterone). Once bound to the appro-
ENDOCRINOLOGY OF HUMAN BEHAVIOR priate receptor, physiological changes can be induced,
including both rapid (e.g., progesterone altering the
As a complementary approach to functional questions inhibitory neuorotransmitter g-aminobutyric [GABA]
concerning human behavior, a focus on endocrine activity) and longer-acting (e.g., estradiol-facilitating
mechanisms highlights some of the proximate ways gene expression) effects.
in which human behavior occurs. Endocrine mechani-
sms play important roles in the expression of human
behavior. The endocrine system helps co-ordinate HUMAN HORMONES AND BEHAVIOR
behavior by serving as a key system of communication EXAMPLES
within the body (see Chapter 8 of this volume). The
endocrine system incorporates information from both With this general background on the evolution and
within and outside the body to help generate appropri- endocrinology of behavior in mind, let us now turn to
ate responses. Hormonal systems can guide an indivi- a series of human behavioral endocrinology examples.
dual toward behaviors appropriate for its condition These are examples focused on sex differences and
(e.g., age, nutritional status, disease status) and social reproductive behavior. This focus thus emphasizes
context (e.g., availability of mates, infant caretaking). examples closely tied to survival and reproductive
The endocrine system consists of ductless glands success, the ultimate currency in a Darwinian world.
that release hormones into the body to effect responses For each of these examples, I begin with a question.
at specific tissues elsewhere in the body (Reed Larsen In these studies, I present primarily human data. My
et al., 2003; Nelson, 2005). While this classic view of phylogenetic bias may be excusable here because
hormone action has many exceptions, this straightfor- this volume focuses on human evolutionary biology.
ward view captures key points of it. In the course of Moreover, the literature on hormones and behavior
hormone release, complex feedback loops emerge. For consists of elegant field and experimental research on
example, the hypothalamus releases gonadotropin- species like voles and rhesus monkeys that researchers
releasing hormone (GnRH), in turn facilitating the commonly extrapolate to humans. Here, we skip the
pituitary to release gonadotropins that in turn lead extrapolation and proceed directly to humans.
280 Peter B. Gray
WHAT IS THE HORMONAL BASIS OF SEX androgens promote development of secondary sexual
DIFFERENCES IN HUMAN BEHAVIOR? characteristics such as underarm hair and sebaceous
glands (which can manifest as acne).
Sex differences exist because they have been favored by Against this backdrop of human sex differentiation,
natural selection, including sexual selection. Over evo- roles for other genes, both on sex and autosomal
lutionary time, females and males have faced different chromosomes, have been identified (Arnold, 2002).
selective pressures to maximize survival and repro- The involvement of some of these other genes suggests
ductive success, leading to the kinds of sex differences slight modifications to the picture above about sex
in behavior described below. A complementary ques- differentiation. Moreover, species differences among
tion to the functional origins of sex differences in mammals exist (e.g., masculinization of the mouse
behavior is to ask about the proximate mechanisms brain, unlike that of an Old World monkey or ape
underpinning them. The fundamental mechanisms brain, involves estradiol bound to estrogen receptors).
underlying human sex differences have been elegantly Nonetheless, we do quite well employing the standard
shown (Migeon and Wisniewski, 1998; Vilain and scenario above to understand the fundamental ways
McCabe, 1998; Nelson, 2005). Centuries of experience human sexes differ.
castrating male domesticated animals and twentieth- One other central concept to the role of hormones
century endocrinology experiments (e.g., castration in human behavioral sex differences should be high-
and hormone replacement studies on laboratory lighted: the distinction between organizational and
rodents) laid the nonhuman groundwork for under- activational effects (Nelson, 2005). Organizational
standing the role of hormones in sex differences. The effects typically refer to permanent effects of hormones
story of human hormonal bases to sex differences is occurring early in life, whereas activational effects
yet another remarkable story of biological conserva- refer to more transient behavioral effects of changes
tion: the mechanisms differentiating human males in hormone levels. To illustrate the distinction, if we
and females look much like those of a typical mammal. were to inject testosterone into a mouse fetus during a
The process of differentiating males from females sensitive period early in life, we might “organize” its
begins with the sex chromosomes. Males possess brain as masculine; injecting testosterone into that
an X and Y chromosome and females two X chromo- same male’s adult brain might demonstrate short-lived
somes. A gene on the Y chromosome – the SRY gene “activational” effects too on male behavior.
(for sex determining region of the Y chromosome) – This background on human sex differentiation,
encodes a protein that causes the initially undif- documenting the crucial roles played by sex steroids,
ferentiated fetal gonads to become testes. As the underlies many of the sex differences in human behav-
testes develop, they begin secreting testosterone and ior that have been observed. Consider, for a moment,
Müllerian inhibiting hormone (MIH) at around week some of the best-documented sex differences in beha-
12 of gestation. Testosterone “tells” other undiffer- vior. Taken from several exhaustive reviews of human
entiated tissues to develop male phenotypes (e.g., pro- sex differences (Maccoby, 1998; Archer and Lloyd,
state gland, penis). In many cases, testosterone is first 2002; Lippa, 2002; Hines, 2004; Cohen-Bendahan
converted to a more potent androgen, dihydrotestos- et al., 2005; Nelson, 2005), these are displayed in
terone (DHT), which binds to the androgen receptor in Table 16.1. The directionality and effect sizes given in
appropriate tissues and thereby leads to the develop- Table 16.1 are drawn from these reviews, with effect
ment of male phenotypes. The MIH secreted by the sizes in some cases estimated by Cohen’s d statistic
testes induces the Müllerian duct system to regress. (number of standard deviations differentiating males
So in the absence of testicular hormones promo- and females) and in other cases more subjective
ting male phenotypes, undifferentiated structures will means. These patterns represent distributions (e.g., a
develop as female phenotypes. Such observations have given female may not differ from a given male) that can
led to the concept of females as the default sex (an also be situated in a broader social context (e.g., the
undifferentiated individual will become female in the magnitude of the sex difference in openness to sexual
absence of substances promoting maleness). This char- behavior varies according to demographic and other
acterization largely holds for the role of hormones factors [Schmitt, 2005]).
early in life. However, at puberty, hormones play cen- Several types of evidence convincingly demonstrate
tral roles in promoting female and male phenotypes that the human behavioral sex differences shown in
respectively (Ellison, 2001). At puberty, estrogens in Table 16.1 can largely be traced to hormonal effects.
women promote secondary sexual characteristics like There are five key types of evidence. The first is that
sex-specific regional fat deposition but also neural experimental research on closely related organisms
mechanisms underlying behavior. Androgens in males like mice, rats, and rhesus macaques commonly
also propel male secondary sexual characteristics, shows that comparable sex differences can be traced
including those involved in behavior. In both sexes, to organizational and activational effects of hormones
TABLE 16.1. Human sex differences in behavior

Providing vivid testimony of such effects, changes
in cognition, mood, and behavior experienced by
Male/female transsexuals while taking hormones to change their
Behavior patterning Effect size
sex have been described (Roughgarden, 2004).
Physical aggression M>F Large To illustrate these various lines of evidence impli-
Direct care of children F>M Large cating hormones in human behavioral sex differences,
Verbal fluency F>M Large take rough-and-tumble play as an example. Experi-
Toy preferences (e.g., males – Large ments with rhesus monkeys support the masculinizing,
and balls; females and organizational, effects of prenatal androgens. So
and dolls) do human cases of atypical development. Some girls
Rough-and-tumble play M>F Very large presenting with congenital adrenal hyperplasia, char-
Preference for boys as M>F Very large acterized by steroid enzyme abnormalities, have
playmates unusually high androgen levels; some of these same
Preference for girls as F>M Very large girls display more masculine play patterns as children.
playmates
Hence, several lines of evidence like these highlight the
Risk-taking behavior M>F Small
roles of hormones in accounting for sex differences in
Socioemotional behavior F>M Medium human behavior (Hines, 2004; Nelson, 2005).
in groups
Decoding nonverbal F>M Medium
behavior
WHAT ARE THE HORMONAL CORRELATES
Task-oriented behavior M>F Medium
in groups OF HUMAN PAIR BONDING AND
Active nonverbal behavior/ M>F Large PARENTAL CARE?
body movement
Openness to sexual behavior M > F Large Long-term bonds between adult mates (pair bonds)
Orientation toward same-sex M > F Large appear to be a derived feature of human behavior
dominance hierarchy arising, perhaps in the genus Homo, within the past
Sexual coercion (e.g., rape) M>F Large 1.8 mya (Gray et al., 2004). Fossil evidence suggests a
Sexual attraction to males F>M Very Large reduction in body size dimorphism consistent with a
Sexual attraction to females M>F Very Large tendency toward reduced male–male contest competi-
tion and rise in pair bonding (Flinn et al., 2005),
though new fossil evidence questions whether these
(Nelson, 2005; Wallen, 2005). For example, rhesus trends began around 1.8 mya or more recently with
female play patterns can be masculinized with andro- archaic Homo sapiens around 0.5 mya (Lordkipanidze
gen administration early in life. The second line of et al., 2007). Regardless of the exact timing of the
evidence is correlational human research. Here, as an origin of human pair bonds, however, these are none-
example, weak, yet positive correlations between adult theless noteworthy because they occur in only about
male testosterone levels and physical aggression have 5% of mammalian species, and are absent in our
been observed (Book and Quinsey, 2005), suggesting closest living relatives, common chimpanzees and
activational differences in testosterone play some role bonobos (Reichard and Boesch, 2003). Changes in
in the sex difference in physical aggression. The third male parental investment (e.g., provisioning and/or
line of evidence involves clinical cases of atypical direct care of children) may have arisen at this same
human development (Cohen-Bendahan et al., 2005). juncture, or perhaps more recently in our lineage.
For example, XY individuals with a nonfunctional If asking about the hormonal bases of human pair
androgen receptor appear and behave largely like bonding and parental care, we can turn to research on
females, implicating androgens in phenotypic mascu- sheep, rats and voles – where most of the relevant and
linization. A fourth line of evidence refers to human experimental research has been conducted. This body
hormonal interventions leading to unintended conse- of research has focused on roles of the peptide hor-
quences. As an example, women taking progestins in mones oxytocin and vasopressin (Carter, 1998; Young
the 1960s and 1970s to improve pregnancy symptoms and Wang, 2004). In nonhuman animals, oxytocin and
unintentionally exposed their fetuses to androgenic prolactin facilitates maternal care and, less consist-
effects of these; the exposed offspring reported a higher ently, adult pair bonds; effects of oxytocin and prolac-
likelihood of using physical aggression than controls, tin are more clearly recognized in females, but also
indicative of organizing influences of androgens on appear sometimes in males. In nonhuman animals,
physical aggression. A fifth line of evidence refers to vasopressin is involved in courtship, male–male com-
human hormonal interventions, usually undertaken petition, and mate and offspring guarding, with its
for clinical, cosmetic, or quality-of-life reasons. effects more pronounced among males (Storm and
282 Peter B. Gray
Tecott, 2005). Here, we draw inspiration from nonhu- blunting her responsiveness to stressors that might
man animal functional and proximate considerations otherwise interfere with maternal care.
to briefly review the hormonal correlates of human While oxytocin plays a role in human maternal
pair bonding and parental care. We concentrate on care, it also seems to be involved in human pair
whether oxytocin and vasopressin play roles in human bonding. In fact, some of the neuroendocrine mechan-
pair bonding and parental care, but also take brief isms involved in parental care appear homologous to
tours to investigate the roles of cortisol and prolactin. those involved in pair bonding (Bartels and Zeki,
Oxytocin has classically recognized roles in smooth 2004). Several studies have examined oxytocin levels
muscle contraction, including that involved in uterine of men and women involved in relationships like
contractions and milk release (Sanchez et al., 2009). marriage to ask whether individual differences in rela-
Orgasm also stimulates oxytocin release (Kruger et al., tionship quality are associated with baseline differ-
2003), as do touch and nipple stimulation (Uvnas- ences in oxytocin levels. Women reporting more
Moberg, 1998). Psychological effects of oxytocin frequent hugs in their marital relationships showed
tend to be anxiolytic. Overall, effects of oxytocin have higher oxytocin levels and lower cardiovascular acti-
been characterized as those of a “relaxing, feel-good” vity (Light et al., 2005).
hormone. Other research methods entailing brief interactions
These psychological effects have important func- between male and female partners, measuring oxyto-
tional effects, particularly with respect to promoting cin levels before and after these interactions, have
affiliative social behavior. Increased oxytocin can con- shown that changes in oxytocin levels appear positively
dition rewarding association between sex, touch, and related to pair bonding outcomes. For example,
other interactions with a partner. Neural pathways Grewen et al. (2005) found that both men and women
activating dopamine facilitate these rewarding effects reporting higher partner support had higher oxytocin
in social memory circuits (Young and Wang, 2004). levels before and after a brief behavioral interaction
Moreover, oxytocin tends to downregulate stress with their partner. Cardiovascular effects were more
responsiveness (Uvnas-Moberg, 1998). This may be pronounced in women than men in this study, how-
advantageous by immunizing an individual against ever. Furthermore, Chen and colleagues observed
stressors in favor of focused, calm attention on a social positive correlations between increases in female oxy-
partner. tocin levels and researcher ratings of partner support
Oxytocin may play a role in human maternal care during brief interactions among couples (Sanchez
(Uvnas-Moberg, 1998). Rushes of oxytocin occur et al., 2009).
during uterine contractions, both facilitating birth Given the expectation that oxytocin will have
and setting the stage for rewarding interactions stronger relationships with female behavior, it remains
between a mother and her newborn. Placing a newborn interesting that links between oxytocin and male
on a mother’s chest increases the mother’s oxytocin behavior have also been shown. Several experimental
levels (Matthiesen et al., 2001). In addition to facilitat- interventions relying on intranasal oxytocin have
ing maternal–offspring bonding, these maternal con- observed increased trust (Kosfeld et al., 2005) and
texts of oxytocin release appear to dampen a mother’s effects on social memory (Kirsch et al., 2005) in men,
stress responsiveness. further showing that links between oxytocin and
Mothers appear to have downregulated behavior occur in males too. Even if oxytocin may have
hypothalamus-pituitary-adrenal (HPA) activity com- a longer-standing role in promoting maternal behavior
pared with nonmothers, at least for the first days or (e.g., in mammals), then its effects can carry over not
weeks postpartum (Uvnas-Moberg, 1998). In fact, ele- only to females pair bonded to a mate, but also pair
vated cortisol levels among mothers of newborns bonded males. This is particularly intriguing because
appear positively associated with maternal interest estrogen is known to have facilatory effects on oxyto-
and care of offspring (Fleming et al., 1997; Fleming, cin, another reason to expect relationships between
2005). Aside from this initial window, maternal inter- oxytocin and behavior to be more prominent in women
actions with an infant, including breast-feeding and (Carter, 2007).
touch, increase oxytocin which, in turn, may help Although closely related to oxytocin, vasopressin
reduce stress reactivity. Breast-feeding mothers has quite different physiological and behavioral
showed less HPA activity than control women on an effects. Its classical roles in vasoconstriction and water
exercise stressor test (Altemus et al., 1995) as well as a retention have long been recognized (and given rise to
psychosocial stressor (Heinrichs, 2001), suggesting its alter-ego name of antidiuretic hormone). Psycho-
downregulatory effects of maternal care (and oxyto- logical effects have also been recognized for decades,
cin) on stress responsiveness. The reduced stress including increased anxiety (Landgraf and Holsboer,
responsiveness of mothers may facilitate more relax- 2005). Research on nonhuman animals suggests vaso-
ing, positive interactions with her offspring, while pressin is more likely to be associated with male than
female human behavior since its effects are potentiated facilitate human maternal care as well as both male
by testosterone (Delville et al., 1996) and the vasopres- and female involvement in adult pair bonds.
sin system is sexually dimorphic. Generally, we should Vasopressin appears linked to male–male competition,
expect vasopressin to facilitate adaptive anxiety and but it is premature to draw conclusions regarding a
rapid behavioral responsiveness within contexts of role for vasopressin in human pair bonding and paren-
male–male competition, courtship, and mate- and off- tal care given the paucity of data. In mothers, cortisol is
spring defense. positively associated with initial engagement in inten-
There are remarkably few data on vasopressin and sive offspring care, then cortisol responsiveness
human male social behavior to address whether behav- appears downregulated with maternal care and effects
ioral correlates of vasopressin are consistent with of oxytocin. Prolactin levels appear positively related
expectations. Only three studies in humans have exam- with human paternal care.
ined links between vasopressin and male aggression.
Positive associations between cerebrospinal fluid
Do male testosterone levels differ according
(CSF) vasopressin levels and aggression have been
to relationship status?
observed (Coccaro et al., 1998). Male subjects random-
ized to receive an intranasal spray of vasopressin dis- Testosterone may be adaptively linked with variation
played increased interest in angry faces compared to in male reproductive effort by promoting male–male
males given a placebo spray (Thompson et al., 2004). competition in reproductive contexts, but being lower
A follow-up study by Thompson et al. (2006) suggested in contexts of affiliative pair bonding and paternal care
sexually dimorphic effects of vasopressin adminis- (Wingfield et al., 1990; Ketterson and Nolan, 1999).
tration. Both women and men reporting increased Such theoretical research has considerable empirical
anxiety associated with vasopressin administration, support in many, but certainly not all, vertebrates. This
but women (unlike men) channeled that anxiety into body of research provides one rationale for thinking
more socially affiliative cognition. That is, women human male testosterone levels too might differ
appeared drawn toward positive interactions with according to differential reproductive effort – and we
others when given vasopressin, while males were more can use pair bonding status and paternal care as indi-
primed toward agonistic responses. cators of variation in reproductive effort.
If vasopressin plays a role in male–male aggression, The first human study addressing this question was
we might also expect from nonhuman data elevated published by Booth and Dabbs (1993) based on a
vasopressin during courtship and in contexts of mate- sample of several thousand US Army veterans. They
and offspring-guarding. However, no data, to my found that married men had significantly lower testos-
knowledge, address these expectations in humans. terone levels than their unmarried counterparts.
Roles for at least two other hormones involved in A rapidly growing human literature on the topic of
paternal care have been raised: prolactin and testoster- human male pair bonding, parenting, and testosterone
one. Prolactin stimulates milk production, and is has extended these initial findings to consider pair
responsive to nipple stimulation, orgasm, and psycho- bonding status (not just marital status), paternal care,
logical stressors, among other stimuli. In a variety of and societies outside the United States (reviewed in
taxa, elevated prolactin is associated with paternal care van Anders and Watson, 2006a; Gray and Campbell,
(Ziegler, 2000; Nelson, 2005). In humans, three studies 2009).
have considered prolactin and paternal care. Two stu- Studies in North America have consistently found
dies of highly invested Canadian fathers revealed that men involved in long-term committed relation-
increases in prolactin levels associated with responses ships such as marriage have lower testosterone levels
to infant cries or interactions with a child (Berg and than unpaired men. Initially, the focus had been on
Wynne-Edwards, 2001; Fleming et al., 2002), although marital relationships, with married US men found to
men’s prolactin responses differed according to experi- have lower testosterone levels than single men (Booth
ence and recency of infant interactions (Delahunty and Dabbs, 1993; Mazur and Michalek, 1998; Gray
et al., 2007). In a sample of 43 Jamaican men, fathers et al., 2004a). Three other studies of business school
maintained relatively flat prolactin profiles across a students (Burnham et al., 2003) and undergraduate
20 minute session interacting with an adult female students (McIntyre et al., 2006; Gray et al., 2004b)
partner and youngest child, whereas prolactin levels found that similar differences held for men involved
of single men sitting alone during this time declined in relationships outside of marriage; that is, involve-
(Gray et al., 2007a). In the next section, we consider ment in a committed, romantic relationship, whether
the evidence that lower testosterone levels may be married or not, was associated with lower testosterone
associated with paternal care. levels. Moreover, lower testosterone levels of partnered
To summarize the hormonal correlates of human men were observed among men regardless of whether
pair bonding and parental care, oxytocin appears to they lived in the same city or were engaged in
284 Peter B. Gray
long-distance relationships with their partners (van (Kenyan Swahili: Gray, 2003; Beijing, China: Gray
Anders and Watson, 2007). et al., 2006; Japan: Sakaguchi et al., 2006; Bangladesh:
Extending this body of research to consider pater- Magid et al., 2006). In the two societies in which male
nal care, two studies observed lower, though nonsigni- testosterone levels have been considered with respect
ficant, testosterone levels among paired fathers to polygyny, in one society men with two wives had
compared with married men without children (Gray higher testosterone levels than other men in the sample
et al., 2002; Burnham et al., 2003). Three other studies (Kenyan Swahili: Gray, 2003), whereas in the other
of Canadian fathers showed a role for testosterone in study men with multiple wives had lower testosterone
fatherhood. Two of these found lower testosterone levels (Ariaal of Kenya: Gray et al., 2007b). In Beijing,
levels among fathers compared with control non- China (Gray et al., 2006), a rural village in Dominica
fathers (Berg and Wynne-Edwards, 2001; Fleming (Gangestad et al., 2005a) and in urban Jamaica (Gray
et al., 2002). Storey et al. (2000) found that fathers et al., 2007a), fathers had lower testosterone levels
had lower testosterone levels shortly after birth com- than nonfathers, although this was not true among
pared to men whose babies were about to be born. Bangladeshi men (Magid et al., 2006).
Moreover, Fleming et al. (2002) found that paternal Several factors may help account for the less con-
responsiveness to infant stimuli such as infant cries sistent links between testosterone and relationship
was inversely related to men’s testosterone levels. status outside of North America. If men’s behavior
Several other North American studies have changes little with marriage, and men are uninvolved
observed finer points in the links between testosterone, in direct paternal care, then we would be less likely to
pair bonding and paternal care. Among both Harvard find lower testosterone levels associated with pair
and University of New Mexico undergraduate students, bonding and fatherhood. If acquisition of an additional
those pair bonded men less interested in seeking extra- wife in a polygynous society is better predicted by male
pair mates tended to have lower testosterone levels age, social status, or wealth, then links between pol-
than paired men more interested in extrapair mating ygynous marriage and elevated testosterone may be
(McIntyre et al., 2006). In examining links between dependent on such considerations (and may help
testosterone and marital interactions among a recently account for the discrepant Kenyan results). Even the
wed Pennsylvanian sample, husbands and wives with context of extrapair mating may be differentially linked
similarly low testosterone levels were found to exhibit to finding elevated testosterone (Mazur and Michalek,
more supportive interactions when observed (Cohan 1998) or not (Gray et al., 2006); depending on variation
et al., 2003). A Canadian study extended these findings in how socially sanctioned the pursuit of extrapair
by considering sexual orientation and both men and mates is, including the availability of access to mis-
women: men paired with women and women paired tresses or prostitutes, then perhaps elevated testoster-
with women had lower testosterone levels than their one associated with affairs will only arise where males
unpaired counterparts, but men paired with men and must engage in overt male–male competition and
women paired with men did not show differences in courtship. These considerations suggest that the use
testosterone levels according to partner status (Van of relationship status as a proxy for human male
Anders and Watson, 2006b). mating and parenting effort has less validity in some
Of course, what happens in North America may not sociocultural contexts than others, and may in turn
be representative of what happens elsewhere in the help account for the less consistent findings cross-
world. Human pair bonding and paternal behavior culturally.
vary cross-culturally. In some societies, husbands and While summarizing the human male testosterone,
wives may be highly supportive of each other; in pair bonding and paternal care literature, it is import-
others, as measured by indices such as cosleeping, ant to bear in mind several caveats. Almost all of these
coeating, spending leisure time together, and providing studies have relied on cross-sectional research designs
emotional support, husbands and wives may be quite in which the causal relationships between hormones
aloof (Whiting and Whiting, 1975). Human paternal and behavior remains undefined. In one of the rare
care also exhibits considerable variation both in terms longitudinal designs, men’s testosterone levels
of direct care (e.g., holding and carrying a child) and increased around the time of divorce (Mazur and
indirect care (e.g., defending and provisioning) Michalek, 1998), and we saw above that men’s baseline
(Marlowe, 2000). testosterone predicted paternal responsiveness in a
Perhaps not surprisingly, the cross-cultural Canadian sample; these studies suggest, consistent
research on this topic is less consistent than that from with general hormone-behavior principles, that testos-
North America (Gray and Campbell, 2009). In some terone and men’s social relationships are likely recipro-
societies, monogamously married men have lower tes- cally related to each other. The sample sizes of most of
tosterone levels than unmarried men (Ariaal of north- these studies are modest, at least compared with epi-
ern Kenya: Gray et al., 2007b), but in others they do not demiological studies. The effect sizes (as measured by
percentage differences in testosterone between groups in places where they could meet mates) around the
of men, correlation coefficients, and p values) are also time of ovulation. Finally, the behavioral shift to
modest. Many things happen in different male rela- mating may come at a sacrifice to other activities like
tionships, and variation in testosterone levels com- eating and sleeping. We would expect such behavioral
monly appears to be one of these things – especially shifts around the time of ovulation to be due to effects
in North America. All this said, male testosterone levels of increased estrogen and/or increased androgen levels.
do appear to commonly differ according to relation- Since, after ovulation, physiological mechanisms
ship status – as one might have anticipated. initially act as if fertilization has occurred, we should
expect the latter half of the menstrual cycle, or luteal
phase, to support behaviors appropriate to pregnancy
Does female behavior change across
like increased eating, sleeping, and lower energy
the menstrual cycle?
expenditure (fewer public displays). Moreover, sexual
A tremendous amount of research has recently behavior may decrease relative to an expected periovu-
addressed potentially adaptive changes in human latory peak. Effects during the luteal phase would pre-
female mating psychology, including sexual behavior, sumably be due largely to rising concentrations of
across the menstrual cycle (reviewed in Gangestad progesterone.
et al., 2005b). As one illustration of this tantalizing If fertilization has not occurred, a consequence will
literature, females prefer the scent of more be short-circuiting the endocrine mechanisms that had
symmetrical males around the time of ovulation been acting as if the female were pregnant; behavioral
(Gangestad and Thornhill, 1998). Here, we begin with effects at this time should be viewed as by-products
functional logic predicting changes in several facets of rather than functionally designed. During the late
female behavior including, but not limited to, sexual luteal phase, a transient increase in sexual behavior
behavior across the menstrual cycle. The logic predict- could be expected from the rapidly diminishing physio-
ing changes in female behavior includes behavioral logical support for pregnancy; decreases in caloric
shifts viewed as adaptive as well as behavioral shifts intake might also arise. At the time, both estrogen
viewed as by-products of other traits. Relevant empi- and progesterone levels plummet, suggesting that they
rical evidence is briefly considered below to determine would be implicated in behavioral shifts associated
whether a priori expectations are supported or not with menstruation. Because of the potentiating effects
given the available data. Last, a case is made for of estrogen on oxytocin, premenstrual declines in
more research directed at changes in female behavior oxytocin may also have behavioral effects indirectly
studied across the so-called “reproductive cycle” through decreased oxytocin (Brizendine, 2006).
(pregnancy, postpartum amenorrhea [suppression of So do the expected changes in female behavior
ovulation after birth], cycling). occur across the menstrual cycle? With respect to
An adaptive perspective suggests human female sexual behavior, drawing primarily on North American
behavior should change across the menstrual cycle. and Western European samples, results have been
We might anticipate shifts in key behavioral domains mixed (reviewed in Brewis and Meyer, 2005). In some
such as sexual behavior, relationship dynamics, dietary studies, fluctuations in sexual activity have been
intake, display activities, and sleep. Because the fertile observed, but not consistently. However, arguably two
window is short (1 day), and the life span of sperm in of the best designed studies involving North American
the reproductive tract also short (about 3–5 days), we pair bonded (but not maternal) females, including
would expect selection to have favored female beha- urine collection for hormone assay and cycle phase
viors resulting in successful mating behavior around assignment, did find increases in intercourse fre-
the time of ovulation (Pillsworth et al., 2004). The most quency in the days prior to and around ovulation
straightforward psychological and behavioral evidence (Bullivant et al., 2004; Wilcox et al., 2004). In
of successful mating behavior would be increases in expanding the cross-cultural scope of this research,
female libido, to motivate behavior, and sexual beha- however, we often encounter more evolutionary-
vior (i.e., vaginal intercourse) itself around the time of relevant contexts in which to address this question –
ovulation. As other correlates of successful mating contexts in which females already have children. In a
behavior around the time of ovulation, we might sample of pair bonded, reproductive-age women from
anticipate changes in relationship dynamics among 13 countries (e.g., Guinea, Haiti, Peru) relying on ques-
pair bonded women. Women attached to their partners tionnaire responses to identify cycle phase and sexual
may be more likely to spend time around their mates; activity, no increases in sexual behavior appeared
their mates may also be more likely to mate guard around the time of ovulation (Brewis and Meyer,
them. If women are unpaired or seeking additional 2005). The only patterned sexual behavior across the
mating opportunities, they may engage in more cycle was a reduction during menses, a pattern also
public display (e.g., more likely to flirt or spend time reported in a different cross-cultural survey (Ford and
286 Peter B. Gray
Beach, 1951). Interestingly, several negative predictors orchestrated by hormones, that occur across a “repro-
of sexual behavior observed in Brewis and Meyer’s ductive cycle” (menstrual cycle, pregnancy, postpar-
study were being older, breast-feeding, having more tum amenorrhea). Women residing in human hunter-
children, and being involved in a polygynous (rather gatherer and other natural fertility populations spend
than monogamous) union. the bulk of their reproductive years pregnant or lactat-
Several studies have investigated whether relation- ing – not experiencing decades of continuous men-
ship dynamics (e.g., time spent with a partner, felt strual cycles (Ellison, 2001; Eaton et al., 1994).
commitment to a partner) change across the menstrual Consequently, in addition to examining behavioral
cycle. In a diary study of 38 US women (in which shifts across the menstrual cycle, we should be devot-
women reported self and partner’s behavior daily), ing greater attention to the shifts in female behavior
women reported more mate guarding by their partner across the reproductive cycle. Toward this end, I briefly
around the time of ovulation (Haselton and Gangestad, consider the female behavioral changes we might
2006). Similar patterns emerged from behavioral expect to occur with pregnancy and postpartum
observations in a small, Caribbean village (Gangestad amenorrhea.
et al., 2005a). In a study of UK women, subjects While pregnant, we might expect decreased sexual
reported higher commitment to their relationship on behavior (already pregnant), increased food consump-
cycle days associated with high progesterone levels tion, and decreased activity levels, especially near the
(Jones et al., 2005). time of birth. Hormonal changes associated with
Fessler (2003) has recently reviewed both nonhu- pregnancy, including steady rises in estrogens, andro-
man and human data assessing potential changes in gens, progesterone, dehydroepiandrosterone sulfate
dietary intake and female activity patterns across the (DHEAS), and cortisol, may facilitate some of these
menstrual cycle. In his review, he observed that dietary expectations but also yield by-product behavioral
intake decreased in 10 of 16 studies around the time of effects (Buckwalter et al., 2001; Greenspan and
ovulation – evidence, he noted, that could be viewed as Gardner, 2001). For example, the rising estrogen levels
suggesting adaptive changes in the salience of female (especially estriol) and androgen levels during preg-
motivation at that time. There was mixed evidence nancy may maintain libido and in turn promote sexual
whether female activity patterns shifted across the behavior more than might otherwise be expected
cycle. For example, one study observed an increase in during a time when a female cannot conceive. After
volunteerism around the time of ovulation. In a recent birth, rapid decreases in pregnancy hormones may
exhaustive review of sleep research, no clear, consist- play a role in postpartum depression (Bloch et al.,
ent patterns were observed in sleep patterns across the 2003; Nelson, 2005). Such changes should be viewed
menstrual cycle (Moline et al., 2003). as by-products of pregnancy rather than adaptive. The
What should we conclude about variation in female suppressed gonadal steroid levels during postpartum
behavior across the menstrual cycle? Behavioral effects amenorrhea prevent a new pregnancy during a time
tend to be modest, if they can be measured at all. This when a mother is subject to the metabolic challenges of
observation is consistent with the view that human breast-feeding, with maternal condition and energy
behavior tends to be quite flexible – that conserved balance playing additional roles in the resumption of
endocrine mechanisms operate but with greater cor- menstrual cycles (Ellison, 2001). The dramatic changes
tical control over our behavior than, say, laboratory in hormone levels may interact with perceived social
rodents (Panksepp et al., 2002; Keverne, 2005). support to help account for variation in mood and
Another conclusion is that patterns in female behavior depression postpartum. Reduced sexual activity post-
across the menstrual cycle may be contingent upon the partum thus may be expected, but dietary intakes
contexts in which they are measured. In samples of increased.
young, nulliparous women, we may be more apt to Focusing on sexual behavior, we observe both some
observe periovulatory peaks in sexual behavior than consistent patterns as well as cross-cultural variation
in samples of older women with multiple children pre- in female behavior across the reproductive cycle. Both
sent in the household. As Fessler (2003) reminds us, in the United States (Laumann et al., 1994; Rathus
studies of dietary intake and activity are lacking in et al., 2005) and cross-culturally (Ford and Beach,
societies where food availability is constrained and 1951), pregnant women tend to continue engaging in
where women walk as part of subsistence activities – sexual activity. However, the frequency of sexual acti-
perhaps we are underestimating these latter effects in vity tends to diminish the longer the pregnancy. Inter-
places where these are more meaningful determinants course is commonly avoided the initial weeks
of female reality and reproductive success. postpartum, with resumption of sexual activity quite
From an evolutionary perspective, a focus on variable cross-culturally; in some societies, it is
female behavioral changes across the menstrual cycle avoided for months to years, but this tends to be
overlooks the more dramatic life history shifts, among societies practicing polygyny, meaning that a
husband has alternative sexual outlets (Ford and Beach, interventions for treating social deficits. If
1951). Several reviews primarily of North American testosterone interferes with social relationships, might
studies show that the frequency of sexual behavior tends those individuals taking high doses of exogenous
to be less common postpartum than before pregnancy androgens be compromising their intimate social rela-
(von Sydow, 1999; De Judicibus and McCabe, 2002). tionships? If fluctuations in female sex steroids across
Breast-feeding tends to be negatively associated the reproductive cycle account for variation in sexual
with postpartum sexual behavior, perhaps due to behavior, clinicians might advise patients accordingly.
direct hormone effects (e.g., elevated prolactin helping There are many exciting paths that research on the
suppress sex steroid levels) or other reasons (e.g., a evolution and endocrinology of human behavior
mother feeling less desire for physical contact from might take. The further links to functional imaging
her adult partner) (De Judicibus and McCabe, 2002). (e.g., Bartels and Zeki [2004] on the neural correlates
Fatigue, physical health concerns (e.g., after episiot- of maternal and romantic love, which showed that
omy), and changes in body image also tend to play neural structures rich in oxytocin and vasopressin
common roles predicting postpartum sexual behavior. receptors were activated by subjects viewing photo-
Generally, then, it does appear that patterning of graphs of a romantic partner or one’s child) may pro-
sexual activity is consistent with expectations of vide direct insight into neural actions of hormones
highest frequencies among cycling women, but dimin- (otherwise rarely accessible in humans). The availabi-
ished frequencies with pregnancy (especially advanced lity of minimally invasive hormone measures (in saliva,
pregnancy) and postpartum. Of course, these are quite urine, and finger-prick blood spots) opens the door to
general conclusions, calling for more behavioral data cross-cultural and epidemiological research that would
on women across this important transition in life. otherwise be prohibitive in clinical settings (e.g., meas-
uring hormonal correlates of allocare or aggression in
naturalistic settings). Greater attention to the develop-
CONCLUSIONS mental course of neuroendocrine mechanisms will
illuminate the ways early social experiences “get under
This chapter has provided a taste of the evolution and the skin”; these may include effects of social depriv-
endocrinology of human behavior. Beginning with some ation (Fries et al., 2005), but also more typical early
general principles concerning the evolution of behavior social experiences in various cultural settings (see
and endocrinology, we turned to a set of four examples to Chapter 27 of this volume).
flesh out some of the best empirical evidence document- Indeed, the variable cross-cultural expression of
ing the links between human hormones and behavior. human behavior effectively provides a remarkable set
The work on hormones and human sexual differentiation of “natural social experiments” unprecedented for any
demonstrates elegant, well-documented roles for the other vertebrate. International human migrations and
role of hormones in generating sex differences in human travel increasingly bring this variation close to home
behavior. A nascent literature on the hormonal correlates (e.g., a doctor treating a diverse patient population;
of human pair bonding and parenting has, in several students, business people, and politicians interacting
studies, implicated the peptide oxytocin in maternal care with people of diverse backgrounds). Many research
as well as both male and female pair bonding. A review questions could be addressed based on this variation:
of the human male testosterone, pair bonding, and What are the hormonal correlates of sibling or grand-
parenting literature revealed that pair bonded and pater- parental allocare? What are the hormonal correlates
nal men commonly exhibit lower testosterone levels of human to nonhuman animal interactions (see
than their single counterparts, although these effects Odendaal and Meintjes, 2003)? Do adoptive parents
were more consistent in North American samples. Some show similar hormonal bases of allocare compared with
evidence suggests changes in female behavior across biological parents? In the world of the evolution and
the menstrual cycle, although that evidence is not espe- endocrinology of human behavior, we have learned
cially strong and overlooks the more dramatic, and evo- much recently, but fascinating questions remain.
lutionary relevant, changes in female behavior occurring
across the reproductive cycle.
There are clinical and epidemiological implications DISCUSSION POINTS
of existing human research on the evolution and endo-
crinology of behavior. When parents face the decision 1. Why do boys engage in more rough-and-tumble
of what gender to raise a child of ambiguous sex, play than girls? Provide answers to this question
knowledge of the biological basis of sex differences employing each of the four perspectives high-
may inform their decision. Oxytocin may facilitate lighted in Tinbergen’s framework.
some of the health benefits of social relationships, in 2. Among hunter-gatherer societies, women spend
turn raising the possibility of oxytocin-based most of their reproductive years pregnant or
288 Peter B. Gray
lactating. Infants are typically nursed two to four Archer, J. and Lloyd, B. (2002). Sex and Gender, 2nd edn.
years. Contrast that reproductive context with one Cambridge: Cambridge University Press.
in which women commonly gives birth by cesarean Arnold, A. P. (2002). Concepts of genetic and hormonal
section, often aided by administration of synthetic induction of vertebrate sexual differentiation in the
oxytocin (e.g., pitocin), to one or two children over twentieth century, with special reference to the brain.
In Hormones, Brain and Behavior, vol. 4, D. W. Pfaff,
the course of their lives, and which they nurse for a
A. P. Arnold, et al. (eds). San Diego, CA: Academic Press,
few months postpartum. What are some potential
pp. 105–135.
behavioral impacts of this latter reproductive scen-
Barkow, J. H., Cosmides, L. and Tooby, J. (eds) (1992). The
ario, both on the mother and offspring, compared Adapted Mind: Evolutionary Psychology and the Generation
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3. Suppose you were designing a clinical trial to tionary Psychology. Princeton: Princeton University Press.
determine whether testosterone supplementation Bartels, A. and Zeki, S. (2004). The neural correlates of
affected family relationships in older men. Why maternal and romantic love. Neuroimage, 21, 1155–1166.
might you expect (or not) that increased testoster- Becker, J. B., Breedlove, S. M., Crews, D. et al. (eds) , (2002).
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testosterone, cortisol, and estradiol levels in men becom-
4. Researchers have pointed out that species differ-
ing fathers. Mayo Clinic Proceedings, 76, 582–592.
ences in pair bonding and paternal care of closely
Betzig, L. (ed.) (1997). Human Nature: a Critical Reader.
related species of voles (small rodents) appear to be
Oxford: Oxford University Press.
underpinned by the oxytocin and vasopressin
Bloch, M., Daly, R. C. and Rubinow, D. R. (2003). Endocrine
systems. What evidence is there that human female factors in the etiology of postpartum depression. Compa-
involvement in long-term pair bonds and maternal rative Psychiatry, 44, 234–246.
care is facilitated by oxytocin? Similarly, what evi- Bolhuis, J. J. and Giraldeau, L -A. (2005). The Behavior of
dence is there that human male involvement in Animals: Mechanisms, Function, and Evolution. Malden,
long-term pair bonds and paternal care is facili- MA: Blackwell.
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5. Imagine you were designing a two-year field issues: a response to Archer et al. Aggressive and Violent
research study to investigate potential shifts in Behavior, 10, 637–646.
female behavior across the menstrual cycle and Booth, A. and Dabbs, J. M. (1993). Testosterone and men’s
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manioc and plantains) living in the Amazon Basin.
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Which behaviors would you seek to examine? How
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Buss, D. M. (2003). Evolutionary Psychology: the New
Science of the Mind, 2nd edn. New Needham, MA: Allyn
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Part III
Reproduction
“The reproduction of mankind is a great marvel and

mystery. Had God consulted me in the matter, I should
have advised him to continue the generation of the
species by fashioning them out of clay.”
Martin Luther (1483–1546)
293
17 Human Mate Choice
David P. Schmitt
From an evolutionary perspective, animal mate choice seen among truly monogamous species, especially
depends in large part on the natural mating system primates (Alexander et al., 1979). Moreover, across
of a species. The natural mating system of humans, foraging cultures – the predominantly polygynous cul-
however, seems at first glance to contain internal con- tures in which humans have spent most of our evolu-
tradictions. On the one hand, humans show several tionary history (Frayser, 1985; Brown, 1991; Pasternak
signs of having a monogamous mating system. et al., 1997) – there are ethnographically pervasive links
For example, humans are highly altricial – we have among men’s status, polygynous marriage, and repro-
prolonged childhoods and rely heavily on extended ductive success (Low, 2000; Turke and Betzig, 1985).
families throughout our life spans (Alexander and In contrast, very few cultures (<1%) have polyandrous
Noonan, 1979). We also appear designed to form marriage systems (Broude and Greene, 1976).
romantic pair bonds, having a dedicated neurochemis-
try of attachment associated with monogamy when
comparisons are made across mammalian species EVOLUTIONARY THEORIES OF MATE CHOICE
(Fisher, 1998; Young, 2003).
On the other hand, humans seem to possess Evolutionary psychologists tend to reconcile these
evolved design features associated with multimale/ seemingly contradictory findings by acknowledging
multifemale or “promiscuous” mating systems. For that humans, like several other species, are probably
example, humans possess psychological and physio- designed and adapted for more than one mating strat-
logical adaptations to sperm competition (Baker and egy (Mealey, 2000; Barash and Lipton, 2001). Specific-
Bellis, 1995; Shackelford and LeBlanc, 2001), such as ally, most evolutionary psychologists view humans as
women’s adaptive timing of extrapair copulations coming equipped with specialized mate choice adapta-
(Gangestad and Thornhill, 1998; Haselton and Miller, tions for both long-term mating (i.e., marriage and
2006), men’s specialized expressions of sexual jealousy extended pair bonding) and short-term mating (i.e.,
(Buss, 2000; Schützwohl, 2006), and the physical struc- promiscuity and infidelity; see Buss and Schmitt,
ture of the human penis serving as a semen displace- 1993). Not all people pursue both mating strategies at
ment device (Gallup et al., 2003). Among men, causal all times. Instead, humans possess adaptive desires,
sex with multiple partners is often viewed as desirable preferences, and behavioral tactics that are differen-
(Symons and Ellis, 1989; Oliver and Hyde, 1993), with tially activated depending on whether a long-term or
most men agreeing to have sex with complete strangers short-term mating strategy is actively being pursued at
when asked in field experiments (Clark and Hatfield, the time (Schmitt et al., 2003; Schmitt, 2005a).
1989). Adaptive patterns of premarital sex, extramar- Most evolutionary theories of human mating
ital sex, and mate poaching by both men and women argue that such a flexible mating design – comprised
have been documented across cultures (Broude and of both long-term monogamous adaptations and
Greene, 1976; Schmitt et al., 2004a). short-term promiscuous adaptations – would have
Moreover, there is further evidence that humans provided important reproductive benefits to humans
are designed, at least in part, for polygynous mating. in our ancestral past, allowing individuals to function-
For example, men and women have sexually differentially respond to a wide range of familial, cultural, and
ated life history traits such as men’s tendencies to be ecological contexts (Pedersen, 1991; Buss and Schmitt,
more physically aggressive, to die much earlier, and to 1993; Lancaster, 1994; Belsky, 1999; Gangestad
physically mature much later than women across all and Simpson, 2000). Evolutionary theories further
known cultures (Archer and Lloyd, 2002; Kaplan and acknowledge that humans can benefit from shifting
Gangestad, 2005). Such sex differences are usually not between long-term and short-term mating strategies
295
296 David P. Schmitt
during their life span, when in different stages of to mate more quickly, at lower cost, and will initiate
romantic relationships, and across the ovulatory relationships with more partners than the heavier-
cycle (Gangestad, 2001; Klusmann, 2002; Schmitt investing parent (Bateson, 1983).
et al., 2002). Thus, humans have evolved the capacity Much of the evidence in favor of Parental Invest-
to follow a mix of different strategies – both long- ment Theory (Trivers, 1972) has come from species
term and short-term – depending on fitness-related where females happen to be the heavy-investing sex
circumstances. (see Clutton-Brock, 1991). In such species, Parental
Most evolutionary psychology approaches further Investment Theory leads to the prediction that sexual
postulate that men and women possess design features selection has been more potent among males. Upon
that cause sex differences in mate choice within long- empirical examination, males of these species tend to
term and short-term mating contexts. For example, display more competitiveness with each other over
when men seek short-term mates they appear motiv- sexual access to heavier-investing females, and to
ated by adaptive desires for sexual variety – desires that exhibit more intrasexual competition through greater
lead them to functionally pursue numerous mating aggressiveness, riskier life history strategies, and
partners and to consent to sex relatively quickly com- earlier death than females (Archer and Lloyd, 2002;
pared to women (Clark and Hatfield, 1989; Symons Trivers, 1985). Lesser-investing males also exhibit rela-
and Ellis, 1989; Okami and Shackelford, 2001; Schmitt tively indiscriminate intersexual mate choice, often
et al., 2003). Women’s short-term mating motivations seeking multiple partners and requiring less time
appear not to be rooted in the desire for numerous before initiating sex than females do (Geary, 1998).
sexual partners and seem focused, instead, on other Perhaps the most compelling support for Parental
factors such as obtaining select men who display dom- Investment Theory (Trivers, 1972), however, has come
inance, intelligence, or creativity (i.e., show high from “sex-role reversed” species. In species where
genetic quality; see Gangestad and Thornhill, 1997; males are the heavy-investing parent, the processes of
Regan et al., 2000; Penton-Voak et al., 2003). As a sexual selection are thought to have been more potent
consequence, evolutionary approaches predict men’s among females. Females of these species vie more fer-
and women’s mate choices and attraction tactics will ociously for sexual access to heavy-investing males
differ in important ways, especially within the context and require little from males before consenting to sex.
of short-term mating. Most evolutionary theories of Evidence of this form of sexual differentiation has been
human mate choice are based on the assumption that documented among such “sex-role reversed” species
the sexes will differ in some ways, an assumption as the red-necked phalarope, the Mormon cricket,
that can be traced to the logic of Parental Investment katydids, dance flies, water bugs, seahorses, and a var-
Theory (Trivers, 1972). iety of fish species (Alcock, 2001). Parental Investment
Theory, therefore, is not a theory about males always
having more interest in indiscriminate sex than
Parental Investment Theory
females. Instead, it is a theory about differences in
According to Parental Investment Theory (Trivers, parental investment obligations systematically relating
1972), the relative proportion of parental investment – to sex differences in mate choice and relationship
the time and energy devoted to the care of individual initiation.
offspring (at the expense of other offspring) – varies Among humans, many men invest heavily in their
across the males and females of different species. children by teaching social skills, emotionally nurtur-
In some species, males provide more parental investing children, and investing in their offspring both
ment than females. In other species, females possess resources and prestige. Nevertheless, men incur much
the heavy-investing burdens (e.g., most mammals; lower levels of obligatory or “minimum” parental
Clutton-Brock, 1991). Sex differences in parental investment in offspring than women do (Symons,
investment burdens are systematically linked to pro- 1979). Women are obligated, for example, to incur
cesses of sexual selection (Darwin, 1871). The sex that the costs of internal fertilization, placentation, and
invests less in offspring is intrasexually more competi- gestation in order to reproduce. The minimum physio-
tive, especially over gaining reproductive access to logical obligations of men are considerably less –
members of the opposite sex. That is, the lesser- requiring only the contribution of sperm. Furthermore,
investing sex is reliably more aggressive with their all female mammals, including ancestral women,
own sex, tends to die earlier, tends to mature later, carried the obligatory investments associated with
and generally competes for mates with more vigor lactation. Lactation can last several years in human
than the heavier-investing sex (Alcock, 2001). Further- foraging environments (Kelly, 1995), years during
more, the lesser-investing sex of a species is intersexu- which it is harder for women than men to reproduce
ally less discriminating in mate choice than the and invest in additional offspring (Blurton Jones,
heavier-investing sex. The lesser-investing sex is willing 1986). Finally, across all known cultures human males
Human Mate Choice 297
typically invest less in active parenting effort than influences, regnant cultural norms, and other features
females (Low, 1989; Munroe and Munroe, 1997). of social and personal context (see also Gangestad
This asymmetry in parental investment should and Simpson, 2000; Schmitt, 2005a, 2005b).
affect human mate choice, with the lesser-investing
sex (i.e., men) displaying greater intrasexual competi-
tiveness and lower intersexual “choosiness” in mate EVOLUTION OF SEX DIFFERENCES
preferences. Numerous studies have shown that men IN MATE CHOICE
exhibit greater physical size and competitive aggres-
Sex differences in long-term mating
sion (Archer and Lloyd, 2002), riskier life history strat-
egies (Daly and Wilson, 1988), relatively delayed Although SST views both sexes as having long-term
maturation (Geary, 1998), and earlier death than and short-term mating strategies within their reper-
women do across cultures (Alexander and Noonan, toire, men and women are predicted to psychologically
1979). In addition, men’s mate preferences are, as pre- differ in what they desire (i.e., mate choice) and in
dicted, almost always less “choosy” or discriminating how they tactically pursue (i.e., initiate) romantic rela-
than women’s, especially in the context of short-term tionships. In long-term mate choice, the sexes are
mating (Kenrick et al., 1990; Regan et al., 2000). predicted to differ in several respects. Men are
Because men are the lesser-investing sex of our hypothesized to possess long-term mate choice adap-
species, they also should be more inclined toward ini- tations that place a greater premium on signals of
tating low-cost, short-term mating than women. fertility and reproductive value, such as a woman’s
Human sex differences in the desire for short-term youth and physical appearance (Symons, 1979; Buss,
sex have been observed in studies of sociosexuality 1989; Jones, 1995; Kenrick and Keefe, 1992; Singh,
(Simpson and Gangestad, 1991; Jones, 1998; Schmitt, 1993). Men also prefer long-term mates who are sexu-
2005a), motivations for and prevalence of extramarital ally faithful and are capable of good parenting (Buss
mating (Seal et al., 1994; Wiederman, 1997), quality and Schmitt, 1993). Women, in contrast, are hypothe-
and quantity of sexual fantasies (Ellis and Symons, sized to place a greater premium when long-term
1990), quality and quantity of pornography consump- mating on a man’s status, resources, ambition, and
tion (Malamuth, 1996), motivations for and use of maturity – cues relevant to his ability for long-term
prostitution (McGuire and Gruter, 2003), willingness provisioning – as well as his kindness, generosity, emo-
to have sex without commitment (Townsend, 1995), tional openness – cues to his willingness to provide for
willingness to have sex with strangers (Clark, 1990; women and their children (Ellis, 1992; Feingold, 1992;
Clark and Hatfield, 1989), and in the fundamental dif- Cashdan, 1993; Townsend and Wasserman, 1998;
ferences between the short-term mating psychology of Buunk et al., 2001; Brase, 2006).
gay males and lesbians (Bailey et al., 1994). Clearly, Conversely, men who display cues to long-term
sex differences in parental investment obligations provisioning, and women who display youthfulness,
have an influence on men’s and women’s fundamental tend to be the ones that are most effective at initiating,
mate choices and basic reproductive strategies. enhancing, and preserving monogamous mating
relationships (Buss, 1988; Tooke and Camire, 1991;
Walters and Crawford, 1994; Landolt et al., 1995;
Sexual strategies theory
Hirsch and Paul, 1996; Schmitt, 2002). From an evolu-
Buss and Schmitt (1993) expanded on Parental Invest- tionary perspective, the differing qualities that men
ment Theory (Trivers, 1972) by proposing Sexual Strat- and women preferentially respond to are thought to
egies Theory (SST). According to SST, men and women help solve the adaptive problems that men and women
have evolved a pluralistic repertoire of mating strat- had to overcome throughout human evolutionary his-
egies. One strategy within this repertoire is “long-term” tory (Schmitt and Buss, 1996). Of course, in our ances-
mating. Long-term mating is usually marked – for both tral past men and women also faced similar problems
men and women – by extended courtship, heavy invest- of mate choice, leading to little or no sex differences in
ment, pair bonding, the emotion of love, and the dedi- some domains (Buss and Schmitt, 1993).
cation of resources over a long temporal span to the Numerous survey and meta-analytic studies
mating relationship and any offspring that ensue. have confirmed many of the major tenets of SST,
Another strategy within the human mating repertoire including the fact that men and women seeking long-
is “short-term” mating, defined as a relatively fleeting term mates desire different attributes in potential part-
sexual encounter such as a brief affair, a hook-up, or ners (e.g., Cunningham et al., 1995; Jensen-Campbell
one-night stand. Which sexual strategy or mix of strat- et al., 1995; Graziano et al., 1997; Regan, 1998a, 1998b;
egies an individual pursues is predicted to be contin- Li et al., 2002; Kruger et al., 2003; Urbaniak and
gent on factors such as opportunity, personal mate Kilmann, 2003). Several investigators have replicated
value, sex ratio in the relevant mating pool, parental or confirmed SST-related findings using nationally
representative, cross-cultural, or multicultural samples mate preferences of one sex should have a substantive
(Feingold, 1992; Knodel et al., 1997; Sprecher et al., impact on the effectiveness of attraction tactics used
1994; Walter, 1997; Schmitt et al., 2003). Other investi- by the opposite sex. If men possess an evolved prefer-
gators have validated key SST hypotheses concerning ence for physical attractiveness, the argument goes,
sex differences in long-term mate choice using nonsur- women should be more engaged than men at using
vey techniques such as studying actual mate attraction, mate initiation and attraction tactics that manipulate
online dating services, speed dating contexts, personal physical attractiveness. Conversely, if women prefer
advertisements, actual marital choices, spousal con- resources more than men do, men should be more
flicts, and which traits lead to divorce (Betzig, 1989; engaged than women at using resource-related tactics
Wiederman, 1993; Kenrick et al., 1994; Townsend and of initiation and attraction. Empirical evaluations
Wasserman, 1998; Salmon and Symons, 2001; Schmitt have supported this aspect of sexual selection in
et al., 2001; Dawson and McIntosh, 2006; Hitsch et al., humans. For example, Buss (1988), Tooke and Camire
2006). These experimental, behavioral, and naturalistic (1991), and Walters and Crawford (1994) all demon-
methodologies suggest evolutionary-supportive find- strated that women are judged more effective than men
ings are not merely stereotype artifacts or social desir- when using appearance-related tactics of initiation and
ability biases limited to self-reported mate choice. attraction, whereas men are judged more effective than
Hitsch et al. (2006) recently examined 22 000 mem- women when using resource-related tactics of roman-
bers of an online dating service and tested for sex tic initiation and attraction (for a meta-analysis of
differences in the attributes of members who were mate attraction results, see Schmitt, 2002).
sought out and contacted by other members as pro- Perceived sex differences in physical appearance
spective partners versus those who were not. For and resource-related tactic effectiveness have also been
female members, physical attractiveness (as judged documented within more specialized rating contexts of
from a photograph) accounted for 30% of the variance romantic attraction. Buss (1988) found sex differences
in whether men contacted them. For men, physical in effectiveness ratings of appearance and resource-
attractiveness accounted for 18% of the variance. related tactics when used by men and women to both
In contrast, women’s income accounted for 4% of the attract and retain a long-term marital partner (see also
variance in whether men contacted them. For men, Flinn, 1985; Bleske-Rechek and Buss, 2001). Schmitt
income accounted for 7% of the variance. When com- and Buss (1996) documented sex differences in per-
bining physical attractiveness and income as predict- ceived tactic effectiveness across both self-promotion
ors, researchers found for women that having high and competitor derogation forms of mate attraction (see
income could not make up for having relatively low also Greer and Buss, 1994; Walters and Crawford,
or even average levels of physical attractiveness. How- 1994). Schmitt and Buss (2001) found sex differences
ever, a man of average attractiveness was considered in perceived appearance and resource-related mate
just as desirable as the most attractive men if he made attraction within the specialized context of obtaining
at least $205 500 per year (Hitsch et al., 2006). a long-term mating partner who is already in a rela-
Kenrick et al. (1994) demonstrated a double disso- tionship, what they called the context of mate poaching
ciation of “contrast effects” in that experimental expos- (see also Bleske and Shackelford, 2001; Schmitt and
ure to physically attractive women tended to lessen a Shackelford, 2003). Whether researchers ask people
man’s commitment to his current relationship partner. directly, observe their real-life behavior, or subtly look
However, exposure to physically attractive men had for indirect effects, the pervasive range of sex differ-
no effect on women’s commitment to their current ences in long-term mating psychology supports the
partners. Conversely, when women were exposed to evolutionary perspective on mate choice.
targets who had high status and resource-related attri-
butes, this lessened women’s (but not men’s) commit-
Sex differences in short-term mating
ment to their current romantic partners. Kenrick et al.
(1994) argued that this indirect research method not According to SST, both sexes are hypothesized to
only confirms self-reported mate preference findings, pursue short-term mateships in certain contexts,
but further shows that men’s and women’s evolved but for different reproductive reasons that reflect sex-
mate preferences unconsciously influence men’s specific adaptive problems (Buss and Schmitt, 1993).
and women’s satisfaction and commitment over the For women, the asymmetry in obligatory parental
long-term course of relationships (see also Buss and investment (Symons, 1979; Trivers, 1972) leaves them
Shackelford, 1997; Little and Mannion, 2006). little to gain in reproductive output by engaging in
Another indirect effect of sex-differentiated mating indiscriminate, short-term sex with high numbers of
desires can be found in the context of relationship partners. Women can reap evolutionary benefits from
initiation and romantic attraction. According to short-term mating (Hrdy, 1981; Greiling and Buss,
Sexual Selection Theory (Darwin, 1871), the evolved 2000); however, women’s psychology of short-term
mate choice appears to center on obtaining men of but less than 20% of women, expressed desires for
high genetic quality rather than numerous men in multiple sexual partners (Schmitt et al., 2003). This
high-volume quantity (Smith, 1984; Gangestad and finding supports the key SST hypothesis that men’s
Thornhill, 1998; Banfield and McCabe, 2001; Li and short-term mating strategy is very different from
Kenrick, 2006). women’s and is based, in part, on obtaining large
For men, the potential reproductive benefits from numbers of sexual partners.
short-term mating with numerous partners can be pro- Other findings from the cross-cultural study by
found. A man can produce as many as 100 offspring by Schmitt et al. (2003) documented that men universally
mating with 100 women over the course of a year, agree to have sex after less time has elapsed than
whereas a man who is monogamous will tend to have women do, and that men from all world regions expend
only one child with his partner during that same time more effort on seeking brief sexual relationships than
period. In evolutionary currencies, this represents a women do. For example, across all cultures nearly 25%
strong selective pressure – and a potent adaptive of married men, but only 10% of married women,
problem – for men’s short-term mating strategy to reported that they are actively seeking short-term,
center on obtaining large numbers of partners (Schmitt extramarital relationships (see also Wiederman,
et al., 2003). Obviously, 100 instances of only one-time 1997). These culturally universal findings support the
mating would rarely produce precisely 100 offspring; view that men evolved to seek large numbers of
however, a man mating with 100 women over the course sex partners when they pursue a short-term mating
of a year – particularly repeated matings when the strategy. Some women also pursue short-term mates.
women are nearing ovulation and are especially inter- However, when women seek short-term mates they are
ested in short-term mating (Gangestad, 2001) – would more selective and tend to seek out men who are phys-
likely have significantly more offspring than a woman ically attractive, intelligent, and otherwise possess
mating repeatedly with 100 interested men over the high-quality genes (Buss and Schmitt, 1993; Gangestad
course of a year. and Thornhill, 1997, 2003).
According to SST, three of the specific design fea-
tures of men’s short-term mating psychology are:
(1) men possess a greater desire than women do for a EVOLUTION OF INDIVIDUAL DIFFERENCES
variety of sexual partners; (2) men require less time to IN MATE CHOICE
elapse than women do before consenting to sexual
intercourse; and (3) men tend to more actively seek The previous section addressed the evolutionary
short-term mateships than women do (Buss and psychology of how men and women choose and initate
Schmitt, 1993). This suite of hypothesized sex differ- short-term and long-term mating relationships.
ences has been well supported empirically. For Another important question is when and why an indi-
example, Schmitt et al. (2003) documented these fun- vidual man or woman would choose to pursue a long-
damental sex differences across 10 major regions of term mateship versus a short-term mateship. Several
the world. When people from North America were theories have suggested that personal circumstances –
asked “Ideally, how many different sexual partners including stage of life, phenotypic quality, local
would you like to have in the next month?” over 23% ecology – play an adaptive role in shaping or evoking
of men, but only 3% of women, indicated that they people’s strategic mating choices (Buss and Schmitt,
would like more than one sexual partner in the next 1993; Gangestad and Simpson, 2000). Among the more
month. This finding confirmed that many men, important sex-specific personal characteristics that
and few women, desire sexual variety in the form of affect mating strategies are men’s overall mate value
multiple sexual partners over short time intervals. and women’s ovulatory status.
Similar degrees of sexual differentiation were found
in South America (35.0% vs. 6.1%), Western Europe
Mating differences within men
(22.6% vs. 5.5%), Eastern Europe (31.7% vs. 7.1%),
Southern Europe (31.0% vs. 6.0%), the Middle East According to SST (Buss and Schmitt, 1993), men pos-
(33.1% vs. 5.9%), Africa (18.2% vs. 4.2%), Oceania sess a menu of alternative mating strategies that they
(25.3% vs. 5.8%), South/Southeast Asia (32.4% vs. can follow. Whether a man chooses to pursue a short-
6.4%), and East Asia (17.9% vs. 2.6%). These sex differ- term or long-term mating strategy (or both) may
ences also persisted across a variety of demographic depend, in part, on his status and prestige. In foraging
statuses, including age, socioeconomic status, and cultures, men with higher status and prestige tend to
sexual orientation. Moreover, when men and women possess multiple wives (Betzig, 1986; Borgerhoff
who reported actively pursuing a short-term mating Mulder, 1987, 1990; Cronk, 1991; Heath and Hadley,
strategy were asked whether they wanted more 1998), and in so doing polygynous men are able to
than one partner in the next month, over 50% of men, satisfy aspects of both their long-term pair bonding
desires and short-term “numerous partner” desires. (sometimes in addition to long-term mating) whereas
In most modern cultures, men with high status are women strategically prefer a single monogamous
unable to legally marry more than one woman. How- mateship. An important determinant of individual
ever, they are more likely to have extramarital affairs mate choice, therefore, is overall mate value in the
and to practice de facto or “effective” polygyny in the mating marketplace, with men of high mate value
form of serial divorce and remarriage (Brown and and women of low mate value more likely to pursue
Hotra, 1988; Fisher, 1992; Buss, 2000). Given an equal short-term mating strategies.
sex ratio of men and women in a given culture, this According to Strategic Pluralism Theory (Ganges-
results in other men – namely those with low status tad and Simpson, 2000), men should also be more
and prestige – being limited to monogamy in the form likely to engage in short-term mating when they
of one wife. Some low-status men are left with no wives exhibit the physical characteristics most preferred by
at all and may be forced to resort to coercive, promis- women who desire a short-term mate, especially those
cuous-mating strategies (Thornhill and Palmer, 2000). traits indicative of high genetic quality. Higher facial
Consequently, an important source of individual vari- symmetry, for example, is indicative of low genetic
ation in men’s mate choice and relationship initiation mutation load in men, and women adaptively prefer
tactics is status and prestige. facial symmetry when pursing short-term mates
Whether a man follows a more short-term or long- (Gangestad and Thornhill, 1997). This is because one
term oriented mating strategy depends on other factors of the key benefits women can reap from short-term
as well, many of which relate to the man’s overall value mating is to gain access to high-quality genes that they
in the mating marketplace (Gangestad and Simpson, might not be able to secure from a long-term partner
2000). A man’s “mate value” is determined, in part, by (Gangestad, 2001).
his status and prestige. It is also affected by his current Evidence that physically attractive men adaptively
resource holdings, long-term ambition, intelligence, respond to women’s desires and become more promis-
interpersonal dominance, social popularity, sense of cuous comes from other sources, as well. For example,
humor, reputation for kindness, maturity, height, men who possess broad and muscular shoulders, a
strength, and athleticism (Chagnon, 1988; Ellis, 1992; physical attribute preferred by short-term oriented
Pierce, 1996; Miller, 2000; Nettle, 2002). women (Frederick et al., 2003), tend toward short-term
Most studies of men in modern cultures find that, mating as reflected in an earlier age of first intercourse,
when they are able to do so as a result of high mate more sexual partners, and more extrapair copulations
value, men choose to engage in multiple mating rela- (Hughes and Gallup, 2003). In numerous studies,
tionships. For example, Lalumiere et al. (1995) Gangestad and his colleagues have shown that women
designed a scale to measure overall mating opportun- who seek short-term mates place special importance
ities. The scale, similar to overall mate value, included on the physical attractiveness of their partners,
items such as “relative to my peer group, I can get dates and that physically attractive men are more likely to
with ease.” They found that men with higher mate pursue short-term mating strategies (Thornhill and
value tended to have sex at an earlier age, to have a Gangestad, 1994, 1999; Gangestad and Thornhill,
larger number of sexual partners, and to follow a more 1997; Gangestad and Cousins, 2001).
promiscuous mating strategy overall (see also Landolt Some research suggests that genetic and hormonal
et al., 1995; James, 2003). predispositions may affect men’s mate choice and
Another potential indicator of mate value is the relationship initiation strategies (Bailey et al., 2000).
social barometer of self-esteem (Kirkpatrick et al., Much of this research focuses on the moderating
2002). Similar to the results with mating opportunities, effects of testosterone (Dabbs and Dabbs, 2000).
men who score higher on self-esteem scales tend to For example, married men, compared to their same-
choose and to successfully engage in more short-term age single peers, tend to have lower levels of testoster-
mating relationships (Walsh, 1991; Baumeister and one (Burnham et al., 2003), though this is not true
Tice, 2001). Indeed, in a recent cross-cultural study among married men who are also interested in concur-
by Schmitt (2005b), this revealing trend was evident rent extrapair copulations or short-term mateships
across several world regions. The same relationship (McIntyre et al., 2006). Men who are expectant fathers
was usually not evident, and was often reversed, and hope to have children only with their current part-
among women in modern nations (see also Mikach ner have relatively low testosterone (Gray et al., 2002),
and Bailey, 1999). That is, women with high self- whereas men possessing high testosterone tend to have
esteem were more likely to pursue monogamous, more sexual partners, to start having sex earlier, to
long-term mating strategies. These findings would have higher sperm counts, to be more interested in
seem to support Parental Investment Theory (Trivers, sex, to divorce more frequently, and are more likely to
1972), in that when mate value is high and people are have affairs (Alexander and Sherwin, 1991; Udry and
given a choice, men prefer short-term mating Campbell, 1994; Mazur and Booth, 1998; Manning,
2002). The root cause of this mate choice variability their psychology to that of a short-term mating strat-
may lie in early testosterone exposure and its effects on egist. It has also been shown that women who are
the activation of men’s short-term mating psychology. nearing ovulation find the pheromonal smell of sym-
Exposure to high testosterone levels in utero causes metrical men more appealing than when women are
increased masculinization of the human brain and less fertile (Gangestad and Thornhill, 1998; Rikowski
increased testosterone in adulthood (Manning, 2002; and Grammer, 1999), that women who mate with more
Ridley, 2003). If men’s brains are programmed for symmetrical men have more frequent and intense
greater short-term mating in general (Trivers, 1972; orgasms (Thornhill et al., 1995), and that men with
Symons, 1979), this would lead to the hypothesis attractive faces have qualitatively better health (Shack-
that those who are exposed to higher testosterone in elford and Larsen, 1999) and semen characteristics
utero would be more likely to develop short-term (Soler et al., 2003). Finally, women appear to dress
mating strategies in adulthood. In women, though, more provocatively when nearing ovulation (Grammer
other factors appear to adaptively influence mating et al., 2004), though women near ovulation also reduce
strategy choice. risky behaviors associated with being raped, especially
if they are not taking contraception (Bröder and
Hohmann, 2003).
Mating differences within women
Overall, there is compelling evidence that women’s
Women’s desires for engaging in sexual intercourse mating strategies shift, from a long-term mating
tend to vary across their ovulatory cycles. On average, psychology to a more short-term oriented mating
women’s desires for sex peak during the late follicular psychology, precisely when they are the most fertile.
phase, just before ovulation when the odds of becom- It is possible that these shifts reflect women seeking
ing pregnant would be maximized (Regan, 1996). high-quality genes from extrapair copulations while
It was once thought that this shift in sexual desire maintaining a long-term relationship with a heavily
evolved because it increased the probability of having investing partner (Gangestad, 2001; Haselton and
conceptive intercourse in our monogamous female Miller, 2006).
ancestors. However, several studies have now docu- Additional individual differences and personal situ-
mented that women’s short-term desires for men with ations may be linked to adaptive variability in women’s
high-quality genes actually peak in the highly fertile mate choices and relationship initiation strategies.
days just before ovulation (Gangestad and Thornhill, For example, short-term mating strategies are more
1997; Gangestad, 2001; Haselton and Miller, 2006). likely to occur when in adolescence, when one’s part-
For example, women who are interested in short- ner is of low mate value, when one desires to get rid of
term mating tend to prefer men who are high in dom- a mate, and when one has recently divorced – all situ-
inance and masculinity (Buss and Schmitt, 1993), as ations where short-term mating may serve specific
indicated by testosterone-related attributes such has adaptive functions (Cashdan, 1996; Greiling and Buss,
prominent brows, large chins, and other features of 2000). In some cases, short-term mating seems to
facial masculinity (Mueller and Mazur, 1998; Perrett emerge as an adaptive reaction to early developmental
et al., 1998; Penton-Voak and Chen, 2004). Short-term experiences within the family (Michalski and Shackel-
oriented women may prefer these attributes because ford, 2002). For example, short-term mating strategies
facial markers of testosterone are honest indicators of are more likely occur among women growing up in
immunocompetence quality in men (Gangestad and father-absent homes (Moffit et al., 1992; Quinlan,
Thornhill, 2003). During the late follicular phase, 2003) especially in homes where a stepfather is present
women’s preferences for men with masculine faces (Ellis and Garber, 2000). In these cases, the absence of
conspicuously increase (Johnston et al., 2001; Penton- a father, and presence of a stepfather, may indicate to
Voak et al., 2003), as do their preferences for masculine young women that mating-age men are unreliable.
voices (Puts, 2006), precisely as though women are In such environments, short-term mating may serve
shifting their mating psychology to follow a more as the more viable mating strategy choice once in
short-term oriented strategy around ovulation. adulthood (see also Belsky, 1999).
A similar ovulatory shift can be seen in women’s Finally, some have argued that frequency-depend-
preference for symmetrical faces. Women who gener- ent or other forms of selection have resulted in differ-
ally pursue a short-term mating strategy express ent heritable tendencies toward long-term versus
strong preferences for male faces that are symmetrical, short-term mating (Gangestad and Simpson, 1990).
perhaps because facial symmetry is indicative of There is behavioral genetic evidence that age at first
low mutation load (Gangestad and Thornhill, 1997). intercourse, lifetime number of sex partners, and
During the late follicular phase, women’s preference sociosexuality – a general trait that varies from
for symmetrical faces increases even further (Gangestad restricted long-term mating to unrestricted short-term
and Cousins, 2001), again as though they have shifted mating – are somewhat heritable (Bailey et al., 2000;
Rowe, 2002). However, most findings suggest heritabil- be responded to if men are to remain competitive in the
ity in mate choice and mating strategy is stronger in courtship marketplace.
men than in women (Dunne et al., 1997). Using data from sex ratio fluctuations over time
within the United States, Pedersen (1991) marshaled
a compelling case for a causal link between sex ratios
and human mating strategies (see also Guttentag and
EVOLUTION OF CULTURAL DIFFERENCES Secord, 1983). For example, high sex ratio fluctuations
IN MATE CHOICE have been historically associated with increases in
monogamy, as evidenced by lower divorce rates and
Sex ratios and human mating
men’s greater willingness to invest in their children.
In addition to sex and individual differences in mating Low sex ratios have been historically associated with
strategies, mate choices and attraction behaviors indexes of short-term mating, such as an increase in
appear to vary in evolutionary-relevant ways across divorce rates and a reduction in what he termed female
cultures (Frayser, 1985; Kelly, 1995; Pasternak et al., “sexual coyness.” In a recent cross-cultural study
1997). Pedersen (1991) has speculated that the relative (Schmitt, 2005a), national sex ratios were correlated
number of men versus women in a given culture with direct measures of basic human mating strategies
should influence mating behavior. Operational sex across 48 nations in an attempt to test Pedersen’s
ratio can be defined as the relative balance of mar- (1991) theory. As expected, cultures with more men
riage-age men versus marriage-age women in the local than women tended toward long-term mating, whereas
mating pool (Secord, 1983). Sex ratios are considered cultures with more women than men tended toward
“high” when the number of men significantly outsizes short-term mating (see also Barber, 2000).
the number of women in a local culture. Sex ratios are
considered “low” when there are relatively more
Attachment and human mating
women than men in the mating market. In most cul-
tures women tend to slightly outnumber men, largely Several combinations of life history theory (Low, 1998)
because of men’s polygyny-related tendency to have a and attachment theory (Bowlby, 1969) have suggested
higher mortality rate (Daly and Wilson, 1988). Never- that certain critical experiences during childhood
theless, significant variation often exists in sex ratios play a role in the development of human mating
across cultures, and within cultures when viewed over strategies (Belsky, 1999). Perhaps the most prominent
historical time (Guttentag and Secord, 1983; Grant, of these theories is a life span model developed by
1998). Belsky et al. (1991). According to this model, early
Pedersen (1991) argued that a combination of social experiences adaptively channel children down
Sexual Selection Theory (Darwin, 1871) and Parental one of two reproductive pathways. Children who
Investment Theory (Trivers, 1972) leads to a series of are socially exposed to high levels of stress – especially
predictions concerning the effects of sex ratios on insensitive/inconsistent parenting, harsh physical
human mating strategies. According to sexual selection environments, and economic hardship – tend to
theory, when males desire a particular attribute in develop insecure attachment styles. These children
potential mating partners, females of that species tend also tend to physically mature earlier than those chil-
to respond by competing in the expression and provi- dren who are exposed to less stress. According to
sion of that desired attribute. Among humans, when Belsky and his colleagues, attachment insecurity and
sex ratios are especially low and there are many more early physical maturity subsequently lead to the evolu-
women than men, men should become an especially tionary-adaptive development of what is called an
scarce resource that women compete for with even “opportunistic” reproductive strategy in adulthood
more intensity than normal (see also Guttentag and (i.e., short-term mating). In cultures with unpredict-
Secord, 1983). able social environments, it is therefore argued, chil-
When combined with the parental investment dren adaptively respond to stressful cues by developing
notion described earlier in which men tend to desire the more viable strategy of short-term mating.
short-term mating (Trivers, 1972), this leads to the Conversely, those children exposed to lower
hypothesis that humans in cultures with lower sex levels of stress and less environmental hardship tend
ratios (i.e., more women than men) should possess to be more emotionally secure and to physically
more short-term oriented mating strategies. Con- mature later. These children are thought to develop a
versely, when sex ratios are high and men greatly out- more “investing” reproductive strategy in adulthood
number women, men must enter into more intense (i.e., long-term mating) that pays evolutionary divi-
competition for the limited number of potential female dends in low-stress environments. Although the causal
partners. Women’s preferences for long-term mono- mechanisms that influence strategic mating are most
gamous relationships become the key desires that must prominently located within the family, this model also
suggests that certain aspects of culture may be related of mate choice and relationship initiation – differ in
to mating strategy variation (see also Belsky, 1999). adaptive ways across sex, individual circumstance, and
A closely related theory has been proposed by cultural context.
Chisholm (1996). Chisholm argues that local The sexes differ significantly in their adaptations
mortality rates – presumably related to high stress for short-term mate choice. Men’s short-term mating
and inadequate resources – act as cues that faculta- strategy is based primarily on obtaining large numbers
tively shift human mating strategies in evolutionary- of partners, being quick to consent to sex, and more
adaptive ways. In cultures with high mortality rates actively seeking brief sexual encounters. Women’s
and unpredictable resources, the optimal mating strat- short-term strategy is more heavily rooted in obtaining
egy is to reproduce early and often, a strategy related to partners of high genetic quality, including men who
insecure attachment, short-term temporal orienta- possess masculine and symmetrical features. Both
tions, and promiscuous mating strategies. In cultures sexes desire long-term monogamous partners who are
that are physically safe and have abundant resources, kind and understanding, but men place more emphasis
mortality rates are lower and the optimal strategy is to on youth, and women on social status, when consider-
invest heavily in fewer numbers of offspring. In safer ing a long-term mate.
environments, therefore, one should pursue a long- Individual differences in mate choice within each
term strategy associated with more monogamous sex appear to emerge as adaptive responses to key
mating. Collectively, the Belsky et al. (1991) and personal circumstances. Men high in social status and
Chisholm (1996) theories can be referred to as a “devel- mate value, for example, tend to pursue more short-
opmental-attachment theory” of human mating term oriented mating strategies than other men, and
strategies. highly valued men strive for polygynous marriages
Numerous studies have provided support for where possible (or serial marriages where polygyny is
developmental-attachment theory (Moffit et al., 1992; illegal). Women nearing ovulation tend to manifest
Belsky, 1999; Ellis and Garber, 2000; Barber, 2003; desires indicative of their short-term mating psych-
Quinlan, 2003). In a recent attempt to test developmen- ology, expressing more potent mate choice for mascu-
tal-attachment theory, Schmitt et al. (2004b) measured line and dominant men and being more sensitive to the
the romantic attachment styles of over 17 000 people pheromones of symmetrical men.
from 56 nations. They related insecure attachment Features of culture and local ecology influence the
styles to various indexes of familial stress, economic differential pursuit of long-term versus short-term
resources, mortality, and fertility. They found over- mating strategies. In cultures with high stress levels
whelming support for developmental-attachment and high fertility rates, insecure attachment and
theory. For example, nations with higher fertility rates, resulting short-term mating psychologies in men and
higher mortality rates, higher levels of stress (e.g., poor women may be more common. As a result, in these
health and education), and lower levels of resources cultures evolutionary psychologists expect men to
tended to have higher levels of insecure romantic emphasize obtaining large numbers of partners and
attachment. Schmitt (2005a) also found that short- women to emphasize physical features associated with
term mating was related to insecure attachment across masculinity and symmetry in potential mates (see
cultures. As expected, the dismissing form of insecure Schmitt, 2005a). Finally, the relative sex ratio of men
attachment was linked to short-term mating in men versus women in the local mating pool may play a
and fearful/preoccupied forms of insecure attachment causal role in generating differences in mate choice
were linked to short-term mating in women. These behavior both over historical time and across the many
findings support the view that stressful environments diverse forms of human culture.
cause increases in insecure romantic attachment,
increases presumably linked to short-term mating
strategies (see also Kirkpatrick, 1998). DISCUSSION POINTS
14. What features of mate choice and romantic

CONCLUSIONS attraction in humans show the most sexual differ-
entiation, and what features show a high degree
From an evolutionary perspective, humans seem to of sexual similarity? What adaptive problems
possess psychological adaptations related to monog- faced by humans over the ancestral past explain
amy, polygyny, and promiscuity. It appears that sexual differentiations in mate choice?
humans evolved a pluralistic mating repertoire, organ- 15. How would a shift toward higher levels of short-
ized in terms of basic long-term and short-term mating term mating influence a culture? For example, if
psychologies. The activation and pursuit of these women were to engage in increasingly more
mating psychologies – including concomitant patterns short-term mating over time, how would women’s
evolved short-term mate preferences come to Baumeister, R. F. and Tice, D. M. (2001). The Social Dimen-
more greatly influence a culture? How would sion of Sex. Needham Heights, MA: Allyn and Bacon.
men’s evolved short-term mate preferences influ- Bateson, P. (ed.) (1983). Mate Choice. Cambridge: Cambridge
ence a culture experiencing a shift toward a short- University Press.
term mating system? Belsky, J. (1999). Modern evolutionary theory and patterns
of attachment. In Handbook of Attachment, J. Cassidy and
16. Can short-term mating that results from insecure
P. R. Shaver (eds). New York: Guilford, pp. 141–161.
parent–child attachment serve adaptive func-
Belsky, J., Steinberg, L. and Draper, P. (1991). Childhood
tions? Describe those functions.
experience, interpersonal development, and reproductive
17. How would a bias in sex ratios due to warfare or strategy: an evolutionary theory of socialization. Child
high rates of male imprisonment (i.e., more Development, 62, 647–670.
women than men) come to influence a culture’s Betzig, L. (1986). Despotism and Differential Reproduction: a
mating behavior? Discuss an example from recent Darwinian View of History. New York: Aldine de Gruyter.
history. Betzig, L. (1989). Causes of conjugal dissolution: a cross-
cultural study. Current Anthropology, 30, 654–676.
Bleske, A. L., and Shackelford, T. K. (2001). Poaching, prom-
iscuity, and deceit: combating mating rivalry in same-sex
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18 Mate Choice, the Major
Histocompatibility Complex,
and Offspring Viability
Claus Wedekind and Guillaume Evanno
INTRODUCTION exist in humans, they are likely to also affect offspring

viability.
Human offspring become independent relatively late in Let us start with a more general question, namely,
life and fitness in our species is therefore critically why is there sex at all? Or: why do we need males in our
linked to the amount and quality of the parental care species? Asexual reproduction is common in many
that children receive. This explains, in evolutionary plants and animals. Thinking harder about the evolu-
terms, why humans generally have a resource-based tionary costs and benefits of sex may help us to better
mating system where both sexes invest substantially understand why mate choice may indeed be strongly
into offspring (Trivers, 1972). Women are expected to linked to genetic aspects, and why mate choice for
prefer men who are likely to provide much parental “high genetic quality” partners may in turn help main-
care in the form of active parenting and/or in the taining sex as an, in evolutionary terms, costly way of
amount of resources they can provide. These men are, reproduction.
in turn, expected to be choosy about the women they
select as mates (Trivers, 1972; Johnstoneet al., 1996).
The present chapter is not about this rather obvious
link between mutual mate choice and offspring sur- SEX, SEXUAL SELECTION, AND INFECTIOUS
vival. Instead, we focus on probably less obvious DISEASES
aspects of mate selection that are likely to influence
offspring viability. These include various genetic For evolutionary biology, explaining the success of
aspects that may play a role, e.g., inbreeding avoidance sexual reproduction has been a challenge because sex
or preference for characteristics that are linked to her- involves a number of enormous disadvantages com-
itable viability or to genes that may be complementary pared to asexual reproduction. The major disadvantage
to the chooser’s own genes. Genes of the major histo- is called “the cost of meiosis” (Williams, 1975;
compatibility complex (MHC) have been intensively Maynard Smith, 1978): a female that reproduces sexu-
studied in this context. The MHC genes play a central ally is only 50% related to her offspring while an asex-
role in controlling immunological self- and nonself ual female transmits 100% of her genes to each of her
recognition (Apanius et al., 1997). The MHC is also daughters. Hence, gene transmission is about twice as
one of the most polymorphic regions of the genome, efficient in asexuals as it is in sexuals. The other evolu-
and it has been found to influence sexual selection. tionary disadvantages of sex are, for example, cellular-
We will outline the various concepts that have been mechanical costs, damages through recombination,
proposed about possible genetic aspects of sexual exposure to risks, mate choice, mate competition, etc.
selection, and we will summarize a number of experi- (Andersson, 1994). Therefore, if asexuals would have a
mental studies on humans and other organisms that similar survival probability as sexuals, a mutation
provide support for one or the other model. We will causing a female to produce only asexual daughters
also briefly discuss the possibility of differential paren- would, when introduced into a sexually reproducing
tal investment, i.e., of life history strategies that take population, rapidly increase in frequency and outcom-
the perceived quality of a present partner and the per- pete sexuals in numbers within few generations
ceived future reproductive success into account. Differ- (Williams, 1975; Maynard Smith, 1978). Obviously,
ential parental investment has been intensely studied this does not seem to happen very often, so sex must
in various animal models. If such life history strategies come with large evolutionary benefits. What might
309
310 Claus Wedekind and Guillaume Evanno
these benefits be? And what are the disadvantages investment into gametes as the result of disruptive
of asexual reproduction? selection: smaller gametes can be produced in greater
One serious disadvantage of asexual clones is that number, and larger gametes provide the later zygote
they are likely to die out after some hundred or thou- with more resources to survive better (Parker and
sand generations because of a fatal mechanism called Baker, 1972). Such anisogamy automatically leads to
“Muller’s ratchet” (Muller, 1932). Muller’s ratchet pre- a race among males to ensure that their sperm find and
dicts that slightly deleterious mutations are accumu- fertilize eggs. This is when sexual selection comes into
lated in asexuals from generation to generation until play. It is expected already in the most primitive sexual
the genome does not code for a viable organism any organisms, and although the difference in egg and
longer and the population goes extinct (Andersson, sperm size can be trivial in more complex organisms
1994). On a first glance it may therefore seem that sex with lactation or intense sexual advertisment, sexuals
must be so successful because recombination followed will probably never get rid of sexual selection (Kokko
by selection can result in the efficient removal of dam- et al., 2006). In order to propagate their genes, individ-
aged genes from generation to generation. However, uals must not only survive natural selection, i.e., all the
such a benefit of sex is likely to have a significant effect lethal threats imposed by harsh climates, predators,
only when it is too late, i.e., after an asexual population pathogens, and competitors, but they must also be
has outcompeted all its sexual conspecifics. Without able to find a mate and withstand competition from
any further benefits of sex, asexuals are expected to rivals of the same sex for access to potential mates.
outcompete sexuals within only few generations They have to be successful in sexual selection. Some-
because of the “cost of meiosis” and the other costs times, females have to compete for access to males and
mentioned above, i.e., sexuals would die out before are chosen by males. However, sexual selection is usu-
Muller’s ratchet drove the asexual population to extinc- ally stronger on the male sex, because males usually
tion (Michod and Levin, 1987; Kondrashov, 1993; have a much higher potential rate of reproduction
Howard and Lively, 1994). Muller’s ratchet itself, there- than females (Cluttonbrock and Vincent, 1991;
fore, cannot explain the evolutionary success of sex. Cluttonbrock and Parker, 1992). Regardless of the dir-
Another set of hypotheses suggests that sex enables ection, sexual selection shapes the evolution of a
the spread or even the creation of advantageous traits. species, and it might even help to maintain sexual
This second category of hypotheses on the evolutionary reproduction itself (Agrawal, 2001; Siller, 2001).
significance of sex requires that the direction of selec- Mate choice (intersexual selection) and competi-
tion is continuously changing, i.e., the main sources tion for mates (intrasexual selection) are two large
of mortality are short-term environmental changes. categories of sexual selection. They both cause a
The condition is especially fulfilled in coevolving number of immediately negative aspects, including
systems such as parasite–host communities. The idea the waste of resources for being attractive (the pea-
is that host resistance genes that are advantageous cock’s tail as a classical example in animals, various
today might become disadvantageous in the near forms of status-signaling in humans) or the risk of
future because parasites evolve to overcome them. injury or distraction from predator surveillance during
Therefore, hosts must continuously change gene com- intrasexual struggles or courtship behavior. Further-
binations, and sex is an efficient means to do so. This more, transmission, maintenance, and growth of many
idea is called the “Red Queen hypothesis” (Jaenike, pathogens are increased during the courtship phase
1978; Hamilton, 1980). Of course, the argument can of their host, either directly by sexual behavior
be turned around to predict that any form of sex and itself (transmittance of ectoparasites or sexually trans-
recombination in parasite populations is maintained mitted microparasites) or indirectly by a reduction
as a diversity-generating mechanism to counteract of immunocompetence of the host (Grossman, 1985;
the rapidly changing selection imposed by the host’s Folstad and Karter, 1992), which may be a conse-
immune system (Gemmill et al., 1997; Wedekind and quence of an adaptive resource reallocation during
Rüetschi, 2000). Hence, the evolutionary conflict the courtship phase, mating, and reproduction
between pathogens and hosts may select for diversity- (Wedekind and Folstad, 1994; Gustafson et al., 1995).
generating mechanisms on both sides and in turn pre- These disadvantages that are associated to sexual
vents both parties from dying out as a direct or indirect selection add to the evolutionary costs of sex men-
consequence of Muller’s ratchet. tioned above.
Sexual reproduction is a very powerful diversity- Sexual selection does not need to be over when
generating mechanism. But there is more to sex than mating has occurred. There are various postcopulatory
just creating diversity, even in evolutionary terms. As selection levels possible, especially in mammals with
soon as we have two different mating types (males and their internal fertilization and their intense mother–
females), different reproductive strategies can evolve. embryo interaction (see points 2–8 in Figure 18.1).
This usually starts with anisogamy, i.e., an unequal Postcopulatory inter-sexual selection (also called
Mate Choice, the Major Histocompatibility Complex, and Offspring Viability 311
is hence a possibility that is discussed for humans

too (see below).
INBREEDING AND INBREEDING DEPRESSION
If sex evolved as a diversity-generating mechanism and

sexual selection as a consequence of conflicts between
and within the sexes, it may not be surprising that mate
choice often takes at least the degree of kinship
between two individuals into account. Mating between
kin not only reduces the efficiency of sex as a diversity-
generating mechanism but also gives rise to inbreeding
depression. Inbreeding depression is the immediately
reduced fitness of inbred offspring that results from
the manifestation of deleterious traits. The more
closely the breeding pair is related, the more homozy-
gous the offspring will be. Therefore, recessive deleteri-
ous mutations will be expressed. The significance of
inbreeding depression has been studied in many
systems. Pedigree and/or molecular data from natural
populations that allow for identifying kinship and
quantifying inbreeding have revealed that inbreeding
18.1. The levels at which females or female reproductive tissue
depression is usually substantial enough to affect indi-
could select for or invest differentially into different offspring
genotypes: (1) male choice; (2) selection on sperm with vidual performance, but it varies across taxa, popula-
the female reproductive tract; (3) egg choice for sperm; tions, and environments. In bird and mammal
(4) the second meiotic division in the egg (that only starts some populations, inbreeding depression usually affects
time after the genetic material of the sperm has entered birthweight, survival, reproduction, tolerance or resist-
the egg); (5) selection on the early embryo by the oviduct;
ance to diseases, predators, and other stress factors
(6) implantation; (7) maternal supply to the developing embryo
and spontaneous or induced abortion; (8) maternal care after (Keller and Waller, 2002). Analogously, in plants it
birth. Figure reproduced from Wedekind (1994). affects seed set, germination, survival, and tolerance
or resistance to stress (Keller and Waller, 2002). Quan-
titative estimates of the effects of inbreeding depres-
“cryptic female choice”) may include selection on sion are, however, often difficult to obtain, because
sperm within the female reproductive tract, nonran- there are a number of potentially confounding factors
dom gamete fusion, a nonrandom second meiotic div- that need to be taken into account.
ision in the egg, and/or selective support of the embryo In the case of humans, matings between first-
or the offspring. Preferences for certain kind of sperm degree cousins are frequent in various cultures, and
have been observed in vertebrates and invertebrates various quantitative estimates of inbreeding depres-
(reviewed in Birkhead, 1996, 2000). In many plants, sion exist. The estimates are quite consistent: Descend-
growth of the pollen tube is often affected by the ants of such pair bondings have on average a 4–5%
stigma and depends on the combination of male and increased probability of not reaching their 10th year
female alleles on the self-incompatibility locus (Jordan of life (Bittles and Neel, 1994; Modell and Darr, 2002).
et al., 2000). In mice (Mus musculus), gamete fusion One could carefully project this estimate to other kinds
and the second meiotic division of the egg is not fully of kin matings, for example brother–sister matings.
random with respect to genetics (Pomiankowski and The average degree of relatedness between first-degree
Hurst, 1993; Wedekind et al., 1996; Rülicke et al., cousins is 12.5%, for half-sibs it is 25%, and for full sibs
1998). Analogous results have been found in other it is 50%. Inbreeding depression might then rise up to a
species (Eberhard, 1996; Zeh and Zeh, 1997), but roughly 20% increased probability of inbred children
Stockley (1997) could not find it in common shrews not reaching their 10th year of life. Other authors esti-
(Sorex araneus). Last but not least, in many mammals mate this increased mortality to 25% (Aoki, 2005).
the outcome of pregnancy may be often depend on the This is obviously a significant reduction in offspring
dam’s perception of the sire’s attractiveness or other viability and fitness that may, however, still be wide-
aspects that may be fitness relevant (Bruce, 1954; spread in many human cultures because of the signifi-
Rülicke et al., 2006). Such differential maternal in- cant social benefits that consanguineous marriages
vestment has been observed in some mammals and often provide (Modell and Darr, 2002). In captive
animals (e.g., in zoos), full-sib matings lead on average the oviduct while sperm from other clones progressed
to about a 33% increased mortality in the offspring to the ovary (Bishop, 1996). Furthermore, a negative
(Ralls et al., 1988). correlation was found between the mating success of
Inbreeding depression is a genetic effect, but it is pairs and their overall genetic similarity (Bishop,
not heritable. If an inbred individual mates with an 1996). In the tunicate Botryllus sp., eggs appeared to
unrelated one, the resulting offspring is not likely to resist fertilization by sperm with the same allele on
suffer from a reduced viability as compared to all other the fusibility locus for longer time than sperm with a
offspring of outbreeding pairs. However, the immedi- different allele on it (Scofield et al., 1982).
ate viability and fitness reduction that is linked to Within vertebrates, a series of fertilization experi-
inbreeding depression is expected to select for mech- ments in mice revealed that gamete fusion is not
anisms that lead to kin recognition and inbreeding random with respect to the sperm’s and the eggs’ geno-
avoidance. Indeed, there are many examples of types (Wedekind et al., 1996; Rülicke et al., 1998).
inbreeding avoidance in animals and humans (Pusey In these studies, mice of two inbred strains that were
and Wolf, 1996). bred to differ only in MHC but otherwise had an iden-
Incestuous matings are in many human societies a tical genetic background. F1s of both strains were
cultural taboo, but these taboos may often be politic- paired or used for in-vitro fertilization experiments,
ally motivated (e.g., to avoid too much accumulation of and the MHC of the resulting blastocysts was analyzed
power), and there is much variation among the various by polymerase chain reaction. The observed nonran-
human societies with regard to this taboo (Thornhill, dom fusion of male and female genetic material could
1991; Scheidel, 1996). Beside such social factors that at least partly be explained by inbreeding avoidance.
influence the rate of inbreeding, there also exists a These first experimental data on mice confirmed previ-
number of more biological factors. Avoidance of kin ous observations of deviations from Mendelian inherit-
as mates often relies on recognition of familiarity ance of some alleles in rats (Palm, 1969, 1970; Hings
(Clarke and Faulkes, 1999; Penn and Potts, 1999). In and Billingham, 1981, 1983, 1985), mice (Potts et al.,
some species, odors that reveal information about 1991), and lizards (Olsson et al., 1996). However, the
highly polymorphic loci seem to play a crucial role in data could also be explained in the light of hypotheses
this recognition of familiarity and hence inbreeding that compete to the inbreeding avoidance hypothesis.
avoidance (Brown and Eklund, 1994; Penn and Potts, We will therefore come back to these examples later.
1999). In humans, the so-called “Westermarck effect”
(Westermarck, 1891) may also play an important role
in avoiding inbreeding. Westermarck postulated that “GOOD-GENES” AND “COMPATIBLE-GENES”
men and women who were raised together in some sort SEXUAL SELECTION
of family-like structure are usually not sexually
attracted to each other, regardless of whether they are Apart from inbreeding avoidance, there are a number
genetically related or not. Shepher (1983), for example, of more sophisticated forms of sexual selection, based
found that marriages among communally reared chil- on general phenotypic appearance or on sexual signals
dren in an Israelian kibbutz were virtually absent. such as odors, certain forms of behavior, fluctuating
Analogous observations in other cultures followed asymmetry, or secondary sexual characteristics. The
(Wolf, 1995), and more recent studies (Lieberman literature usually groups criteria for mate choice into
et al., 2003; Fessler and Navarrete, 2004) found that a three classes (Andersson, 1994): (1) criteria that reveal
history of cosocialization with an opposite-sex individ- direct benefits, such as parental care or nuptial gifts;
ual is linked with a decreased tolerance of other’s inces- (2) “Fisherian traits”, i.e., traits that are attractive to
tuous behaviors. Such effects are stronger in females members of the other sex but do not reveal anything
than in males (Lieberman et al., 2003; Fessler and else (Fisher, 1930); and (3) indicators of “good genetic
Navarrete, 2004), and the effect seems to have, among quality” (Zahavi, 1975; Hamilton and Zuk, 1982;
others, an olfactory basis (Schneider and Hendrix, Grafen, 1990). In the following we concentrate on
2000; Weisfeld et al., 2003). this last class of criteria, because a preference for
Inbreeding avoidance does not need to be confined “good genetic quality” is expected to increase offspring
to mating decisions. Nonrandom gamete fusion with survival while a preference for Fisherian traits is not.
respect to kinship has been observed in various taxa. “Genetic quality” is, in the context of sexual selec-
The ascidian Diplosoma listeranum, for example, is a tion, an umbrella term. It includes “good genes” and
colonial, sessile, marine filter-feeder that disperses “compatible genes” (Neff and Pitcher, 2005). “Good
sperm into surrounding water. Sperm are taken up genes” are alleles that increase fitness directly and, in
and pass via the oviduct to reach oocytes within the principle, independently of the rest of the genome.
ovary. Autoradiography of labeled sperm revealed that If variation in such loci exists within a population,
sperm from the same clone were normally stopped in i.e., when there is variation in fitness that can be linked
to such loci, population studies will show additive gen- (1999) concluded that sexual selection for “good genes”
etic variance for viability, and populations are expected is widespread across vertebrate taxa, but its effect on
to evolve in response to directed selection. “Compatible offspring survival varies. Their meta-analysis revealed
genes” are defined as alleles that increase fitness only that male sexual characters chosen by females on aver-
when in combination with other alleles, i.e., only when age accounted for only 1.5% of the variance in off-
in a specific genotype. Such fitness effects can be due spring viability, but the authors stressed that many of
to epistasis, i.e., due to interactions with alleles on the studies included in their analysis may only partly
other loci, or due to any sort of heterozygote advantage estimate the full fitness consequences of mate choice
(e.g., overdominance) when the allele is paired with a for offspring survival. The effects were generally
specific homologue. In population studies, “compatible- stronger for studies where the target of selection had
gene” effects will be revealed in significant nonadditive been identified than those with an unknown target of
genetic variance for viability: some male–female com- selection. Indeed, more recent experimental studies
binations will then have a higher fitness than other demonstrated that “good genes effect” of mate choice
combinations, regardless of possible “good-genes” can be very strong: optimal mate choice in a whitefish
effects. In principle, alleles that contribute to any kind (Coregonus sp.), for example, would reduce pathogen-
of “good genetic quality” can code for all sort of traits. correlated embryo mortality by 67% as compared to
However, there are good reasons to assume that most random mating (Wedekind et al., 2001). Hence, the
of these alleles play a role in the coevolution between potential effects of pathogen-driven sexual selection
hosts and their pathogens, i.e., that sexual selection for on offspring viability can be, at least in some vertebrate
“good genetic quality” is expected to be pathogen taxa, very significant.
driven. A potential indicator of genetic quality that has
The most important aspect of the interaction been intensely studied is fluctuating asymmetry (FA):
between a pathogen and its host is the virulence an the random deviations from perfect bilateral symmetry
infection is associated with, here defined as the loss sometimes observed on various body parts. Develop-
of fitness the pathogen causes to the host. Although mental instability reveals the tendency of an organism
this definition sounds as if virulence were a specific to be influenced by various stress factors (environmen-
trait of a pathogen, it is not. Rather, it is the result of tal-like pathogens, or genetic-like mutations) during
the interaction between this pathogen and its host development (Thornhill and Gangestad, 2006). Fluctu-
(Bull, 1994; Read, 1994; Ebert and Hamilton, 1996). ating asymmetry can then be considered as a measure-
Sexual reproduction and the different forms of patho- ment of developmental instability. Many studies
gen-driven sexual selection have the potential to provide evidence for a link between FA and mate
increase or decrease virulence. Firstly, as indicated attractiveness (reviewed in Møller and Thornhill,
above, the ability of the host to reproduce sexually 1998; more recent studies include Scheib et al., 1999;
plays a significant if not the most important role here Brown et al., 2005; Little and Jones, 2006). An up-to-
(Ebert and Hamilton, 1996). Sexual reproduction date meta-analysis of studies on humans reported a
(especially in the case of outcrossing) results in a statistically significant global effect size of 0.30 (Pear-
rearrangement of host genes. Pathogen populations son’s r) between facial symmetry and mate attractive-
that have adapted to one host line have to readapt to ness (Rhodes and Simmons, 2007). In these studies,
the next one and so on. Hence, host reproduction by attractiveness was either measured as self-reported
sex leads to the existing pathogen population being reproductive success or by rating. The authors also
suboptimally adapted to their current host population. analyzed the attractiveness of body symmetry separ-
This could typically mean that the pathogens are less ately from face symmetry and found a lower but sig-
virulent than would be expected if they were optimally nificant effect size of 0.14 (P < 0.001). It is, however,
adapted to their host (Ebert, 1994). This benefit of less clear whether there exists a relationship between
sexual reproduction could be amplified by certain FA and mate quality. Rhodes and Simmons (2007) also
forms of mate choice. made a meta-analysis of studies looking at symmetry
Hamilton and Zuk (1982) were the first who sug- and health measured as self-reported health status.
gested that individuals in good health and vigor are They found low and not significant effect sizes both
preferred in mate choice because they are the ones that for facial and body symmetry. The link between paren-
are likely to possess heritable resistance to the predom- tal FA and offspring survival has been rarely investi-
inant pathogens. By preferring healthy individuals one gated (Waynforth, 1998) but one study revealed a
may thereby produce resistant progeny. This could higher FA in mothersof preterm infants (Livshits et al.,
result in subsequent generations of hosts that are 1998). Overall, while the relationship between FA
better adapted to the local pathogens, i.e., that are less and mate attractiveness is well established in humans,
susceptible (Grahn et al., 1998). In a meta-analysis on further investigations are needed to demonstrate a
the available empirical evidence, Møller and Alatalo potential link between FA and mate quality.
A preference for indicators of health and vigor will

lead to populations where all individuals of one sex
have the same mate preference, i.e., the members of
the opposite sex can be ranked in an universally valid
order of attractiveness, and less attractive individuals
would only be taken as mates if the more attractive
ones are not available for some reasons. However, in
some species this prediction does not appear to be
fulfilled (Wedekind, 1994, 2002a; Neff and Pitcher,
2005). This may be, at least partly, due to the fact that
an offspring’s level of resistance depends on both its
mother’s and father’s genetic contribution. At loci that
are important for the parasite–host interaction (e.g.,
immunogenes), certain combinations of alleles may 18.2. Participant of the study by Wedekind et al. (1995) where
be more beneficial than others. If individuals choose the odors of six T-shirts worn by men were evaluated for pleas-
their mates in order to produce such beneficial allele antness, sexiness, and intensity. One T-shirt was unused. Three
of the T-shirts had been worn by men who shared no or very few
combinations, their preferences would have to depend
major histocompatibility complex (MHC) antigens with the
on their own genotypes as well as their partners’ ones woman who judged the odors, while three other T-shirts had
(Wedekind, 1994). As a consequence, individuals with been worn by men who shared as many MHC antigens with the
different alleles would show different preferences, and woman as possible in the study sample. It turned out that
there would be no universally valid order of sexual women who were not using the contraceptive pill at the time
of the experiments preferred the odors of MHC-dissimilar men
attractiveness with respect to signals that reveal herit-
(as predicted from mouse studies [Penn and Potts, 1999]), while
able disease resistance. Sexual selection for such women on the pill preferred the odors of MHC-similar men.
“complementary genes” is therefore expected to lead This preference change could be due to hormones that simulate
to very different dynamics as compared to sexual selec- aspects of pregnancy. Pregnancy is known to change
tion for “good genes.” MHC-linked odor preferences in mice (Manning et al., 1995).
The “compatible-genes” sexual selection hypothesis
usually predicts that dissimilar genotypes are more
attractive to each other, e.g., because mating with dis- Potts et al., 1991; Roberts and Gosling, 2003). They
similar genotypes leads to heterozygous offspring that chose according to their own MHC-types, apparently
may benefit from some sort of heterozygote advantage, to reach certain allele combinations or to avoid certain
as has often been proposed in the case of the MHC allele combinations in the progeny.
(Thursz et al., 1997; Carrington et al., 1999; McClelland Humans can distinguish the odors of two congenic
et al., 2003). It has to be stressed, however, that MHC inbred mouse strains that differ only in their MHC
heterozygotes are sometimes less resistant to infec- (Gilbert et al., 1986), and rodents seem to be able to
tions than expected from the average response of recognize human MHC-types (Ferstl et al., 1992).
homozygotes (McClelland et al., 2003; Wedekind Wedekind et al. (1995) found that women’s preferences
et al., 2005). for male odors correlated with the degree of similarity
Preferences for mates or for sperm of genetically of their own and the men’s MHC type. T-shirt odors
dissimilar types have been observed in different verte- were judged as more pleasant when they were worn
brate taxa. Olsson et al. (1996) found in a population of by men whose MHC genotype was different from that
sand lizards (Lacerta agilis), where most females mate of the judging woman (Figure 18.2). The difference in
with more than one male, that the male’s genetic simi- odor assessment was reversed when the women were
larity to the female correlates with the proportion of taking oral contraceptives (studies by Thorne et al.,
her offspring that he sires: more dissimilar males sire 2002 and Roberts et al. 2008, revealed further effects
more offspring, both in the field and in the laboratory. of oral contraceptives on odor perception). Further-
They concluded that the female reproductive tissue more, the odors of MHC-dissimilar men more fre-
actively selects from genetically dissimilar sperm. So quently reminded the women of their own present or
far, the best example of mate preferences that depend former partners than did the odors of MHC-similar
on the chooser’s own genotype is the mouse and the men. These memory associations suggested that the
effects of genes on the MHC. Mice base their mate MHC or other linked genes influence human mate
choice to a large extent on odors. These odors reveal choice. Later experiments (Wedekind and Füri, 1997;
some of the allelic specificity of the MHC (Yamazaki Thornhill et al., 2003; Santos et al., 2005; Roberts et al.,
et al., 1979, 1983a, 1983b, 1994), and this information 2008) with new combinations of T-shirt wearers and
is often used in mate choice by males and females smellers provided further support of a link between
(Yamazaki et al., 1976, 1988; Egid and Brown, 1989; MHC and body odors (but see Jacob et al. 2002, and
Wedekind’s 2002b, comments on this). When men and to at least one external factor that can vary over time.
women sniffed at male and female odors, there was no In an in vitro experiment with two congenic mouse
significant effect of gender in the correlation between strains, Wedekind et al. (1996) tested whether: (1) eggs
pleasantness and MHC similarity (Wedekind and Füri, select for sperm according to their MHC; and
1997). Carol Ober and her colleagues then found in a (2) whether the second meiotic division of the egg is
large study on American Hutterites that married influenced by the MHC type of the fertilizing sperm
couples were less likely to share MHC loci than (Figure. 18.1). They found that neither egg–sperm
expected by chance, even after incest taboos were stat- fusion nor the second meiotic division is random, but
istically controlled for (Ober et al., 1997), but Hedrick that both processes depend on the MHC of both the egg
and Black (1997) could not confirm the effect in South and the sperm. However, these selection levels did not
Amerindians. See Roberts and Little (2008) for a recent simply select for heterozygous MHC-combinations.
review on the subject. Sometimes the eggs appeared to prefer homozygous
It is still not yet clear whether MHC-correlated combinations, and sometimes they appeared to prefer
mate preferences in mice or in humans optimize the heterozygous combinations. This effect of time was
offspring’s immunogenetics or whether the MHC statistically significant. It seemed that the external
merely serves as a marker of kinship to avoid inbreed- factor that influenced sexual selection was an uncon-
ing (Potts and Wakeland, 1993; Apanius et al., 1997). trolled epidemic by mouse hepatitis virus (MHV).
If the first variant holds, this would further improve The presence of MHV appeared to stimulate a prefer-
host defense against pathogen populations, i.e., it ence for heterozygous combinations, while when
would further reduce the observable level of virulence. absent, the mice seemed to prefer homozygous vari-
However, even if the first variant holds, it remains ants. To test this hypothesis, Rülicke et al. (1998)
unclear what kind of MHC-complementarity is pre- repeated the experiment in vivo with two groups of
ferred, i.e., whether individuals simply prefer other mice: some females were experimentally exposed to
types to ensure a higher proportion of MHC-heterozy- MHV while the others were sham exposed. When
gous offspring (Brown, 1997) because heterozygosity the authors typed the blastocysts of these mice for the
at the MHC appears to be beneficial on average MHC, they found again that infected mice had
(Hedrick and Thomson, 1983; Thursz et al., 1997; more MHC-heterozygous embryos than noninfected
Carrington et al., 1999; but see Lipsitch et al., 2003; mice. This time, the finding was the outcome of an
Wedekind et al., 2005), or whether mate choice aims to experiment designed to test an a priori hypothesis.
reach specific allele combinations that are more bene- Several authors have previously searched for devi-
ficial under given environmental conditions than ations from the expected ratios of MHC-heterozygosity
others (Wedekind and Füri, 1997). At the moment, in the progeny of controlled matings (Palm 1969, 1970;
there are only few indications that such beneficial Hings and Billingham 1981, 1983, 1985; Potts et al.
allele combinations exist. The strong linkage disequi- 1991). They reported a significant variability of MHC-
librium observed between some alleles of the MHC heterozygote frequencies which, however, remained
could be explained by long-term epistatic fitness effects poorly understood because there appeared to be a gen-
(Klein, 1986; Maynard Smith, 1989), but there is still eral inability to replicate previous findings (see discus-
much need for research on the beneficial or deleterious sion in Hings and Billingham 1985). Rülicke et al.’s
aspects of various homo- or heterozygous combin- (1998) results could lead to an explanation for the
ations of MHC-haplotypes under given environmental apparently controversial findings published before,
conditions, i.e., under given pathogen pressures. since they could perform the experiments under
Choice for complementary alleles would be most defined hygienic conditions with a selective and moni-
efficient, i.e., it would result in the highest fitness tored viral infection, i.e., they could control for the
return, if individuals were able to choose their mate factor infection that was not fully controlled for in the
conditionally (Wedekind, 1999). A well-tuned condi- previous studies and that could have influenced their
tion-dependent mate selection could have evolved in outcome. However, it is still not clear whether MHC-
some species because of a nontrivial fitness advantage. heterozygous offspring of the mice strains used in the
Conditional choice would take the present pathogen above experiments have a greater resistance to
pressure into account and would promote allele com- MHV-infection than homozygous variants, and it is
binations in the host that ensure the optimal defense still not known whether homozygous offspring have
against these pathogens. However, this requires higher survival in the absence of MHV. If so, nonran-
physiological achievements that have not been demon- dom fusion of egg and sperm with regard to their
strated so far. respective MHC and to the presence or absence
Two studies on mice suggest that sexual selection of MHV could improve the health of the progeny, i.e.,
takes not only the male and female MHC-genotypes it would decrease the observed level of virulence in
into account, but is also conditional since it responds a locally adapted host-pathogen system.
DIFFERENTIAL PARENTAL INVESTMENT (Weckstein et al., 1991; Ho et al., 1994), to the inter-
birth interval (Ober et al., 1988), to the placenta and
Evolutionary theory predicts that parents invest in baby birthweight (Reznikoff Etievant et al., 1991), and
each offspring according to the potential fitness return to the likelihood of otherwise unexplained spontan-
of that offspring (Fisher, 1930). If, for example, the eous abortions in the first three month of pregnancy,
relative reproductive value of sons and daughters as found in the United States (Beer et al., 1985),
differs for different females or different males, sex Germany (Karl et al., 1989), Japan (Koyama et al.,
allocation theory predicts that females adjust the sex 1991), Finland (Laitinen, 1993), or a Chinese popula-
ratio of their offspring according to their own condition in Taiwan (Ho et al., 1990).
tion or according to their mate’s attractiveness (Trivers
and Willard, 1973). Life history theory also predicts
that parental investment depends on the perceived POSSIBLE GENETIC CONSEQUENCES
mate quality (Williams, 1966). Such conditional paren- OF FREE MATE CHOICE
tal investment was first demonstrated in experiments
and field studies that showed that females increase There are many examples of human interference with
their investment in the current brood when mated with animal and plant reproduction. Free mate choice is
a preferred male (Burley, 1982; Delope and Møller, usually circumvented in many farm animals and
1993; Petrie and Williams, 1993). Increased parental plants, and it is often rather restricted in zoo animals.
effort may lower one’s own survival and future repro- Even in our own species there are cases in which free
ductive potential (Saino et al., 1999). mate choice is at least partly prevented, e.g., for some
Recent studies on birds have identified the mech- cultural reasons. From a genetical point of view, this
anisms of these life history decisions. Some female can also be the case as a result of infertility treatment
birds lay more eggs (Petrie and Williams, 1993) or with some forms of assisted reproductive technology,
larger eggs (Cunningham and Russell, 2000) after especially so in donor insemination and in egg or
copulating with preferred males. In the latter case the embryo donation (donors are usually anonymous),
females produced offspring of better body condition but possibly also in intracytoplasmic sperm injection
when paired with preferred males. Gil et al. (1999) where potential egg choice is not allowed for.
found that females deposit higher amounts of testos- It may be too early to speculate about the evolution-
terone and 5a-dihydrotestosterone in their eggs when ary consequences of such interference in our own
mated to attractive males. In kestrels, maternal hor- species. The implication of sexual selection on para-
mones influence offspring survival (Sockman and site–host coevolution is not well understood in natural
Schwabl, 1999), and in canaries, chick social rank is systems, and it is even less understood in a culturally
positively correlated with the concentration of yolk shaped species like our own one. Moreover, while the
testosterone in the eggs from which they hatched, sug- evidence for cryptic female choice (Figure. 18.1) is
gesting that the development of aggressive behavior of increasingly convincing in some plants and animals,
offspring may be modified by maternal testosterone the evidence for it in humans is only correlational,
(Schwabl, 1993; Schwabl et al., 1997). There is evi- i.e., cause and effects are unclear. The existing data
dence that the effect exists also in somewhat more can therefore be interpreted in various ways (Hedrick,
primitive taxa. The tapeworm Schistocephalus solidus, 1988; Verrell and McCabe, 1990; Wedekind, 1994).
for example, produced large eggs if given the oppor- Assisted reproductive technology is now responsible
tunity to outbreed, but relatively small ones if forced to for tens of thousands of new births annually. Gosgen
reproduce by selfing (Wedekind et al., 1998). et al. (1999) discussed the possibility of genetic costs of
Some data suggest that there is differential paren- assisted reproductive technology in humans. The
tal investment in humans, too. However, in contrast to authors found that the incidence of birth defects in
many of the studies on animals, most evidence that these children is not higher than in those conceived
suggests human differential investment is correl- naturally, and that any other possible negative conse-
ational, i.e., causes and effects are not clear. As men- quence of circumventing free mate choice is at least not
tioned above, the degree of MHC-similarity could be obvious in the context discussed here. However, the
shown to influence mate preferences or aspects of success of assisted reproductive technology may
mate attractiveness in some human populations. Life depend on the respective MHC types of the genetic
history theory may therefore predict that differential parents of an embryo (Weckstein et al., 1991; Ho et al.,
maternal investment is linked to the degree of sharing 1994). Gosgen et al. (1999) called for more research on
of MHC antigens between a couple. Indeed, this degree the impact of new reproductive technologies on individ-
of sharing is linked to the rate of successful pregnan- uals and the population, and whether or not donor
cies after in vitro fertilization or tubal embryo transfer insemination programs should reflect female choice.
Many studies on sexual selection have suggested offspring viability in modern human societies, at least
that genetically dissimilar mates are sexually pre- as long as it is not used as a mechanism for inbreeding
ferred (see examples above), probably because high avoidance.
genetic diversity in the offspring is beneficial. It
should, however, be noted that a preference for gen-
etic dissimilarity could not always be observed (e.g., DISCUSSION POINTS
Yamazaki et al., 1976; Wedekind et al., 1996; Hedrick
and Black, 1997; Rülicke et al,. 1998), and it is not 18. What are the genetic and social costs and benefits
clear whether these exceptions would have led to of various degrees of inbreeding in humans?
higher viability in the offspring under given environ- 19. The idea of “good-genes” sexual selection assumes
mental conditions. that potential mates differ in their heritable via-
bility. What maintains variation in heritable via-
bility over time in our species?
CONCLUSION 20. The idea of “compatible-genes” sexual selection
predicts that some combinations of alleles lead to
Sexual mixing of genes has two main evolutionary fitter offspring. If choice for “compatible-genes”
advantages, namely that recombination followed by lead to offspring that are heterozygous on some
selection results in the efficient removal of deleterious loci, does this mean that heterozygote individuals
mutations, and that it creates genetic diversity which is are generally more attractive in mate choice?
important in evolutionary arms races, especially in 21. If differential maternal investment really exists in
host–pathogen coevolution. It may therefore not be humans, what does it say about the fitness conse-
surprising that mating in nature is often not random quences of mate choice based on attractiveness
with respect to genetics, and that it may often be linked traits?
to host–pathogen coevolution. Different kinds of sexual 22. How important are odors in mate choice today?
selection could have different potential consequences 23. Is it possible that some forms of pregnancy prob-
on offspring viability. A preference for unrelated indi- lems in humans may be induced by body odors?
viduals (i.e., inbreeding avoidance) is already a very If so, what would that mean for therapy?
simple form of sexual selection. Several more sophisti-
cated kinds of sexual selection that can be relevant for
parasite–host coevolution have been proposed, some of ACKNOWLEDGEMENTS
them even after mate choice has occurred, i.e., before, We thank Michael Muehlenbein and the two anonym-
during, and after gamete fusion. These possibilities ous reviewers for suggestions and comments on the
have been investigated in some model species, espe- manuscript, and the Swiss National Science Founda-
cially with respect to the MHC, i.e., to a set of genes tion for financial support.
that are crucial in the parasite–host interaction. More-
over, sexual selection is often connected to life history
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19 Why Women Differ in Ovarian Function:
Genetic Polymorphism, Developmental
Conditions, and Adult Lifestyle
Grazyna Jasienska
VARIATION IN LEVELS OF REPRODUCTIVE the endometrium (Eissa et al., 1986; Dickey et al.,
HORMONES 1993). The endometrium is the lining of the uterus in
which the fertilized egg implants and begins its further
High levels of ovarian steroid hormones in menstrual development. Progesterone is essential for maturation
cycles are crucial for successful pregnancy (Lipson and of the endometrium and a dose-response relationship
Ellison, 1996; Venners et al., 2006) and, as such, are has been described between progesterone levels and
important determinants of female reproductive suc- transformation of endometrium during the second half
cess and evolutionary fitness. However, there are sub- of menstrual cycle (Santoro et al., 2000). Cycles that
stantial differences in mean levels of estradiol and vary in levels of these hormones show corresponding
progesterone between populations, among women variation in the chance of pregnancy. In a group of
within a single population and among menstrual cycles Caucasian women from the United States who were
of a single woman (Figure 19.1) (Ellison et al., 1993; attempting pregnancy, women were more likely to
Jasienska and Jasienski, 2008). For example, urban achieve pregnancy during menstrual cycles with higher
women in the United States have progesterone levels levels of estradiol in the follicular phase (Lipson and
that are on average 65% higher than those of women Ellison, 1996). In this group of women, average estra-
from the Democratic Republic of Congo (Ellison et al., diol levels were associated with a 12% probability of
1993). In a rural population from Poland, as much as conception, while a 37% rise in estradiol levels was
46% of the among-cycle variation in salivary progeste- associated with a 35% probability of conception. In
rone is due to differences among individual women, healthy Chinese women who were trying to conceive,
while the remaining 54% of variation is due to differ- cycles characterized by higher levels of estradiol
ences among cycles of individual women (Jasienska resulted in higher rates of conception (Venners et al.,
and Jasienski, 2008). Such high intercycle variation 2006). Progesterone levels, especially during the mid-
is probably caused by a seasonality of agricultural luteal phase, are also positively correlated with the
workload and is much higher than in nonseasonal, probability of successful conception (Lu et al., 1999).
industrial populations. However, even in urban women While it is well established that, among women
from the United States and the United Kingdom, where from the same population, lower levels of ovarian hor-
lifestyle is less influenced by seasons, progesterone mones lead to a lower probability of conception, it is
levels vary from cycle to cycle (Lenton et al., 1983; less clear if differences in average levels of these hor-
Sukalich et al., 1994; Gann et al., 2001;). mones described for different population can be inter-
The present chapter reviews recent findings about preted the same way. That is, between populations, do
variation in human female ovarian function, and more lower average levels of estradiol and progesterone lead
specifically, the levels of two primary female repro- to lower probability of conception in one population
ductive hormones: 17-b estradiol and progesterone. versus another? It has been suggested that ovarian
These steroids are involved in processes leading to function may have different set-points, depending on
ovulation, fertilization, and implantation of the fertil- lifestyle conditions (Vitzthum, 2001). Women with
ized egg. Their levels are important for successful com- chronically poor energetic conditions would have
pletion of these processes and as such are directly lower levels of ovarian hormones, but that these levels
responsible for the establishment of pregnancy. Estra- would be sufficient for conception to occur. For
diol levels positively correlate with follicle size and egg example, rural Bolivian women conceived during
quality, and are related to morphology and thickness of cycles with mean progesterone levels approximately
322
Why Women Differ in Ovarian Function 323
Luteal progesterone (pmol/L)

450
Woman 1 Woman 2 Woman 3
350
250
150
50
1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8
Month of the study
19.1. Inter-individual and intra-individual differences in mean luteal progesterone levels among
healthy Polish rural women with regular menstrual cycles. Progesterone was measured for each
woman in daily collected saliva samples during six menstrual cycles.
40% lower than the levels measured during conception

Fetal Childhood Adult
cycles of urban US women (Vitzthum et al., 2004). It Genes
environment environment environment
is argued that women living in chronically poor ener-
getic conditions are not expected to have levels of
hormones equally high as women having good ener-
getic conditions (Ellison, 1990; Lipson, 2001). Lower
levels of hormones during the cycle observed in women
from chronically poor environments lead to the longer Ovarian function
waiting time to conception, but conception is still
possible.
It is important to note that comparisons of mean Fertility
levels of ovarian hormones among populations or
among individual women are difficult. One needs to Reproductive
success
make sure that women were in a similar age range,
were selected for participation in a study using similar 19.2. Ovarian function is influenced by genes, developmental
criteria, and that differences in laboratory procedures conditions during fetal and childhood growth, and adult life-
style. Ovarian function, and more specifically, levels of estradiol
do not contribute to variation in hormone levels. In
and progesterone, are important determinants of female
addition, hormonal values from blood or serum are fecundity, and as such directly related to her reproductive
not directly comparable with values obtained from success.
saliva or urine (see Chapter 8 of this volume). In conse-
quence, reliable comparisons of hormone levels can be
made, at present, only for very few populations (Ellison important to emphasize that considerable variation in
et al., 1993; Ellison, 1994; Jasienska and Thune, 2001a). the levels of estradiol and progesterone exists among
cycles in such women, and that substantial variation is
still present even among cycles that are regular and
WHY DO WOMEN AND POPULATIONS DIFFER ovulatory.
IN LEVELS OF HORMONES? Ovarian function is sensitive to changes in lifestyle
and can respond with reproductive suppression, espe-
Levels of hormones are influenced by many factors: cially to changes in energy availability. Reproductive
genes, developmental conditions during fetal and suppression is understood here as any change in
childhood growth, and adult lifestyle (Figure 19.2). It reproductive function which lowers the probability of
is also well established that levels of reproductive hor- pregnancy. When reproductive suppression results
mones change with age. The lowest levels are observed from the presence of environmental stressors, it usu-
in the years past menarche and before the menopause, ally occurs in gradual fashion (Prior, 1985; Ellison,
and the highest levels for women between 25 and 1990): a small reduction in energy intake may cause
35 years of age. For a review of age-related variation low progesterone production in the luteal phase of the
in ovarian function see Ellison (1994). menstrual cycle. A more serious energy limitation may
This chapter does not review variation in hormonal result in the absence of ovulation or even total suppres-
levels due to various diseases or anatomical/ sion of cycling (amenorrhea). The probability of preg-
physiological pathologies, but rather focuses on vari- nancy is, of course, reduced to zero when menstrual
ation in ovarian hormone levels in healthy women. It is cycles are anovulatory or absent. However, it must be
324 Grazyna Jasienska
noted that even during ovulatory cycles characterized impact on ovarian function (Ellison, 2003a, 2003b).
by reduced levels of ovarian steroids, the chances of But the interactive effects of energetic conditions
successful pregnancy are decreased (Eissa et al., 1986; during fetal development and adulthood energetic
McNeely and Soules, 1988; Dickey et al., 1993). conditions on ovarian function in adult women may
be very important. A study of Polish women that used
ponderal index at birth (as an indicator of energetic
CONDITIONS DURING FETAL DEVELOPMENT, conditions during fetal development) also assessed
AND HORMONE LEVELS AT ADULTHOOD levels of mean total daily energy expenditure (as an
indicator of energetic conditions during adulthood)
Relatively little is known about the influence of maternal (Jasienska et al., 2006d). It was hypothesized that size
conditions on the development of offspring reproductive at birth would correlate with the sensitivity of adult
functions. Maternal environment may permanently ovarian function to energetic stress. More specifically,
influence numerous aspects of fetal physiology (see women born with poorer nutritional status should have
Chapters 2 and 30 of this volume), but most research higher sensitivity to energetic stress and lower response
projects have been concerned with physiological thresholds in adulthood than women born in better
changes related to subsequent risk of cardiovascular dis- nutritional status. Higher sensitivity may be indicated
eases, high blood pressure, and insulin metabolism. by a reduction in the levels of estradiol in menstrual
However, prepregnancy weight, weight gain during cycles at a lower threshold of energetic stress.
pregnancy, and newborn size may be indicators of sub- Results of this study indicated that nutritional
sequent reproductive functioning in offspring. status at birth is a predictor of the sensitivity of adult
Several studies support the hypothesis that condi- ovarian function to energetic stress. Physical activity
tions during fetal development, indicated by the size of may suppress ovarian function. However, women who
the newborn baby, have important effects on a woman0 s had a high ponderal index at birth did not exhibit
reproductive physiology (Davies and Norman, 2002). ovarian suppression in response to moderate levels
Girls born small for gestational age have, as adoles- of physical activity at adulthood. They responded with
cents, a smaller uterus and ovaries and reduced rates suppression only to higher levels of physical activity,
of ovulation (Ibanez et al., 2000a, 2000b, 2002). Size at while, in contrast, women who had a lower ponderal
birth may even influence age of menarche and meno- index at birth showed ovarian suppression even under
pause (Cresswell et al., 1997; Adair, 2001). Cycles in mild energetically stressful conditions (Figure 19.3).
women with early menarche may also be characterized
by higher levels of ovarian steroids (Apter, 1996).
While the studies listed above focused on small size
Low activity Moderate activity High activity
for gestational age (usually below 2500 g), variation in
“normal” size at birth may also be related to ovarian 24
function. In healthy Polish women with regular men-
strual cycles, variation in levels of estradiol was related
Estradiol (pmol/L)
to their size at birth (Jasienska et al., 2006e). The 20

ponderal index (calculated as body weight/body
length3) describes fatness at birth and, therefore, can
be used as an indicator of newborn0 s nutritional status. 16
This measure significantly predicted levels of estradiol
in menstrual cycles: mean estradiol was 16.4 pmol/L in
the group of women with low ponderal index, 12
17.3 pmol/L in the group with moderate ponderal
index, and 19.6 pmol/L in the group with high ponderal
First tertile Third tertile
index. These results suggest that conditions during
Tertiles of fatness at birth
fetal life influence physiological mechanisms respon-
sible for production of reproductive hormones in 19.3. Mean (with 95% confidence intervals) levels of estradiol in
women from the first and the third tertiles of fatness at birth (as
adulthood, and may be one of the central causes of quantified by the ponderal index) at three different levels of
interindividual variation in reproductive function mean daily physical activity. At low physical activity, both tertiles
observed in adult women. of fatness at birth had similar levels of estradiol. These tertiles of
Of course, the levels of ovarian hormones in adult fatness also did not differ at high levels of physical activity. Such
women result not only from impact of the fetal envir- activity was associated with reduced estradiol in both groups.
Moderate levels of physical activity, however, were sufficient to
onment, but also from the influences of the adult envir- suppress estradiol levels in women who were relatively skinny at
onment. As discussed later in this chapter, metabolic birth (the first tertile), but not in women relatively fat at birth (the
conditions during adult life have a well established third tertile).
The predictive adaptive response hypothesis was for the effects of potentially confounding factors, like
developed by Gluckman and Hanson (2005) in order sports ability (Paul et al., 2006). Since energy expend-
to explain how physiological adjustments made by a iture resulting from sports participation is one of the
fetus may result from developmental constraints or, most important factors influencing levels of ovarian
alternatively, are adaptive responses to future enviro- hormones, such a variable should be controlled for
nment. It was suggested that the developing fetus (e.g., as a covariate) when investigating a relationship
receives information about past environmental condi- between 2D:4D and hormone levels.
tions that serves as cues for making predictions about
future environmental conditions (Gluckman et al.,
CONDITIONS DURING CHILDHOOD
2005b; Ellison, 2005; Kuzawa, 2005; Jasienska, 2009).
AND OVARIAN HORMONES
Therefore, women who develop under poor in utero
conditions may receive a signal predicting poor envir-
Nutritional conditions during childhood can influence
onmental conditions in adulthood. In these women,
the age at menarche: girls with poor nutritional status
ovarian sensitivity to energetic stress may be more
mature later than those with good nutritional status
acute, so that relatively mild energetic stressors in
(Ellison, 1982, 1990; Vermeulen, 1993). In those that
adulthood (a possible signal of deteriorating environ-
mature early, ovarian hormone levels are higher, in
mental conditions) would result in reproductive sup-
comparison with those that mature late, for at least
pression. Such ovarian suppression, associated with a
several years past menarche (Vihko and Apter, 1984).
reduced probability of conception (Lipson and Ellison,
It is unclear if early menarche somehow changes the
1996), may represent a developmentally plastic, pre-
future trajectory of reproductive physiology or if both
dictive adaptive response, lowering the probability of
age at menarche and hormone levels are independently
conception when prospects for successful gestation are
influenced by nutritional conditions.
poor (Ellison, 2003a; Jasienska, 2003).
Recently, more direct evidence pointed to the
Studies of body asymmetry, finger length ratios
impact of childhood conditions on adult ovarian func-
(2D:4D), and ovarian hormones also reveal an influ-
tion. Nunez-De La Mora et al. (2007) analyzed levels of
ence of the uterine environment on adult ovarian func-
ovarian hormones in Bangladeshi women of repro-
tion. Fluctuating asymmetry (FA), or random deviation
ductive age living in Bangladesh with Bangladeshi
from perfect symmetry expected in bilateral structures
women who migrated to the United Kingdom at differ-
of bilaterally symmetric organisms, may result from
ent points of their lives, and also with Caucasian
the influences of environmental stressors operating
women living in the United Kingdom. Bangladeshi
during fetal development (Moller and Swaddle, 1997;
women who spent their childhood in Bangladesh had
Jones et al., 2001). Results pointing to a relationship
lower levels of progesterone than Bangladeshi women
between FA and reproductive physiology in women are
who migrated to United Kingdom as children, or
preliminary, but such a relationship was indicated
those who were born in the United Kingdom. Those
between breast symmetry and fertility-related traits,
women who migrated as young children (between zero
since women with higher breast symmetry had a
and eight years of age) had significantly higher levels of
higher number of offspring (Moller et al., 1995).
progesterone than those who migrated at later ages.
Another study confirmed this finding and, in addition,
They also exhibited earlier age at menarche and taller
documented an earlier age at first birth for more sym-
adult size. For women who migrated as children (prior
metric women (Manning et al., 1997). A relationship
to menarche), age at migration predicted age at menar-
between FA and ovarian function was also documented
che and average levels of luteal progesterone: early
in Polish women: mean mid-cycle estradiol levels in
migration was associated with earlier maturation and
more symmetric urban women were almost 30%
higher hormone levels at adulthood. Energetic stres-
higher than estradiol levels in asymmetric women from
sors resulting from maintaining immune responses to
the same population (Jasienska et al., 2006b).
high infectious disease burden in Bangladesh was sug-
Digit length ratio (index to ring fingers; 2D:4D) may
gested to be responsible for lower levels of ovarian
also be another marker of uterine conditions, parti-
function in women who remained in Bangladesh and
cularly the influence of androgens on prenatal sex
those who emigrated at later ages.
differentiation (Manning et al., 2002). In women of
reproductive age, estradiol measured in a single serum
sample was positively correlated with 2D:4D (Manning ENERGY METABOLISM DURING ADULT LIFE:
et al., 1998). McIntyre et al. (2007) also identified a ENERGY INTAKE AND PHYSICAL ACTIVITY
positive correlation between right hand 2D:4D and
estradiol, but not progesterone, levels. While the latter The influence of adult lifestyle on reproductive func-
study was advantageous by measuring hormones in tion has been studied intensely (Ellison, 2003b). Levels
daily collected saliva samples, neither study controlled of ovarian hormones are often reduced due to poor
nutritional condition. Negative energy balance, is stronger when weight loss occurs in combination
resulting from either high levels of energy expenditure with exercise (Bullen et al., 1985), or when it occurs
or from low levels of energy intake, correlates with in young women (Schweiger et al., 1989).
reduced levels of ovarian hormones. Variation in ovarian function caused by energetic
Intense exercise and very negative energy balance factors is not restricted to cases of voluntary exercise or
are associated with increased incidence of menstrual dieting in urban women. It has also been described as
disturbances and even total amenorrhea (absence of a result of workload or seasonal food shortages in
cycles) (Prior et al., 1982; Prior, 1985; Broocks et al., women with more traditional lifestyles. Farm women
1990; Rosetta, 1993, 2002; Rosetta et al., 1998;). High in rural Poland have profiles of salivary progesterone
incidence of menstrual disturbances in female endur- that vary with the intensity and duration of their work-
ance athletes has been well documented (Feicht et al., loads (Jasienska, 1996; Jasienska and Ellison, 1998,
1978; Prior et al., 1992; Rosetta, 1993). Such disrup- 2004). Women in Zaire and Nepal show seasonally
tions can be induced in previously untrained women suppressed levels of ovarian steroids associated with
who are subjected to demanding regimes of aerobic changes in workload and energy balance (Ellison et al.,
exercise (Bullen et al., 1985). 1986; Panter-Brick et al., 1993). In Zaire this seasonal
More moderate variation in energy expenditure variation in ovarian function has been implicated as
(e.g., women engaged in various forms of recreational the main cause of observed seasonality in conceptions
exercise) is associated with less dramatic changes in (Bailey et al., 1992).
ovarian function, including lower levels of ovarian Energy expenditure due to sport participation or
hormone, but without the disruption of menstrual pat- occupational work may influence ovarian function
terns, and often even without any change in menstrual independently of negative energy balance. Bullen
cycle regularity (Pirke et al., 1989; Broocks et al., 1990; et al. (1985) investigated the effects of intense physical
Ellison, 1990; De Souza et al., 1998; Jasienska and exercise on ovarian function in previously untrained
Ellison, 1998, 2004; Jasienska et al., 2006f). For women. While women in one group were losing weight
example, weekly running, even at very low distances, during eight weeks of intense training regime, a second
causes changes in the length of the luteal phase of the group of women were receiving controlled diets with
menstrual cycle (Shangold et al., 1979). Recreational enough additional calories to maintain prestudy body
joggers who run on average less than 24 km per week weight. Even though the suppression of ovarian func-
have suppressed levels of salivary progesterone tion was more pronounced in the weight-loss group,
(Ellison and Lager, 1985, 1986; Bledsoe et al., 1990). women who did not lose weight when training also
The incidence of anovulatory cycles in adolescent girls showed evidence of moderate ovarian suppression.
also shows a dose-response relationship to weekly Ovarian suppression has also been documented in
energy expenditure (Bernstein et al., 1987). women who were maintaining stable body weight
Negative energy balance resulting from low energy while running on average 20 km per week (Ellison
intake also influences ovarian function. During the and Lager, 1986). Even though the runners0 menstrual
Dutch famine in the winter of 1944–1945, severe cal- cycles were of similar length as those in the control
oric restrictions resulted in reduced ability to conceive, group, they were characterized by lower levels (and
as indicated by birth records (Vigersky et al., 1977; shorter profiles) of luteal progesterone. In Polish
Painter et al., 2005). Women who lost 15% of initial women, variation in the amount of habitual physical
weight exhibited amenorrhea and disturbances in the activity (as measured by average total daily energy
release of pituitary gonadotropins (Vigersky et al., expenditure) corresponds to variation in estradiol
1977). In young women, caloric restriction (i.e., levels (Jasienska et al., 2006f) (Figure 19.4). Women
dieting) is associated with increased incidence of from the low-activity group had 30% higher estradiol
menstrual disturbances and suppressed ovarian concentration than women from the high-activity
hormone profiles (Pirke et al., 1985). Eating disorders, group.
such as anorexia nervosa and bulimia nervosa are Occupational work that does not necessarily cause
often associated with serious menstrual and hormonal negative energy balance may still result in ovarian sup-
disorders (Becker et al., 1999). Women do not need to pression (Jasienska, 1996; Jasienska and Ellison, 1998,
be thin, however, to develop ovarian suppression in 2004; Jasienska et al., 2006f). Polish women working
response to weight loss. Lower salivary progesterone on their own farms had salivary progesterone levels
profiles have been observed in women who lose only reduced by almost 25% during the months of intense
moderate amounts of mass through caloric restriction harvest-related activities in comparison to months
(Lager and Ellison, 1990). In these women, suppres- with less demanding work. These women were in good
sion of ovarian steroid levels was even more pro- nutritional status (mean body mass index [BMI] of
nounced in the cycle following that in which the 24.4 kg/m2, mean body fat percentage of 27.5) and did
weight loss occurred. Suppression of ovarian function not exhibit negative energy balance as a result of
19.4. Profiles of mean estradiol for groups of

Low activity women with low, moderate, and high levels of
Moderate activity mean daily habitual physical activity. Confidence
35 High activity intervals were omitted for clarity. Reprinted from
Jasienska et al. (2006f).
30
Estradiol (pmol/L)
25
20
15
–8 –6 –4 –2 0 +2 +4 +6 +8
Aligned days of menstrual cycle
intense work. Results of these studies clearly indicate example, in a study which examined women who were
that negative energy balance is not a necessary condi- patients of fertility clinics from the United States and
tion for the occurrence of physical activity-induced Canada, obese women (BMI 27) were three times less
reproductive suppression in women. likely to conceive than women with a BMI between
20 and 25 (Grodstein et al., 1994). Similarly, obese
British women reported more menstrual problems
IS BODY FAT RELATED TO FECUNDITY? and were less likely to conceive than women with lower
body weight (Lake et al., 1997). These obese women
Women with very low and very high body fat levels often experienced pregnancy complications, including
often experience menstrual and hormone level irregu- hypertension. In the United States, the risk of infertility
larities, and thus are less likely to conceive. Several increases from 1.1 among women with a BMI of 22.0–
studies have described a positive or an inverse U-shape 23.9 to 2.7 in women with BMI 32 (Rich-Edwards
relationship between BMI or body fat percentage and et al., 1994). Obese women who are able to lose a
estradiol levels in women (Bruning et al., 1992; Barnett modest amount of weight (even less than 10%) often
et al., 2002; Furberg et al., 2005; Ziomkiewicz, 2006). observe improved menstrual regularity, higher rate of
None of these studies, however, controlled for the ovulation, higher ovarian hormone levels, and, conse-
effects of energy balance. It is possible that variation quently, a higher chance of conception (Falsetti et al.,
in BMI or body fat is correlated with variation in 1992; Clark et al., 1995; Galletly et al., 1996; Norman
energy balance. Many women are able to achieve low and Clark, 1998). Therefore, weight loss is recom-
BMI or low fat percentages due to conscious control of mended for obese women who are unable to become
body size through low energy diet or exercise. These pregnant. Some authors even suggest that weight loss
women are more likely, on average, to be in a state of programs should be offered to women before any other
negative energy balance or have high levels of energy treatments for infertility (Norman et al., 2004).
expenditure. As discussed earlier, both of these factors
have well established suppressive effects on ovarian
function. In further analyses, Ziomkiewicz et al. OVARIAN SUPPRESSION AS AN
(2008) suggested a positive relationship between body EVOLUTIONARY ADAPTIVE PHENOMENON
fat percentage and estradiol levels, but only in women
with positive energy balance, while in women with Ellison (1990, 2003a) proposed that physiological
negative energy balance, body fat did not correlate responses of the reproductive system of contemporary
with ovarian function. women to energetic factors are not pathological, but
An excess of body fat seems to be detrimental to rather reflect important features of human biology
fecundity. Women who are obese or overweight have a during the evolution of modern humans, particularly
lower likelihood of conceiving and suffer more compli- throughout the late Paleolithic era. Human physiology
cations during pregnancy than women of healthy body has remained basically unchanged since this time
weight (Baird et al., 2006; Homan et al., 2007). For (Eaton et al., 1988, 2002), and energetic stressors have
been, and still are, salient features of life in many and Martorell, 1988; National Academy of Sciences
traditional populations (Roberts et al., 1982; Lawrence Committee on Population, 1989; Tracer, 1991; Little
and Whitehead, 1988; Panter-Brick, 1993; Adams, et al., 1992; Winkvist et al., 1992; Miller et al., 1994;
1995; Benefice et al., 1996; Sellen, 2000). Pike, 1999; George et al., 2000), thus negatively
Human female reproduction is energetically expen- affecting her future reproductive potential. Shorter life
sive. Relatively little energy is required to maintain spans in women with many children also suggests that
ovarian and uterine functions. However, resting meta- reproduction may indeed have negative long-term con-
bolic rate rises by 6 12% for several days during the sequences for maternal health (Doblhammer, 2000;
luteal phase (Bisdee et al., 1989; Meijer et al., 1992; Helle et al., 2002; Dribe, 2004; Jasienska et al., 2006c).
Howe et al., 1993; Curtis et al., 1996), and women tend Reproductive suppression in response to tempor-
to increase their caloric intake during the days ary, poor environmental conditions serves to protect
following ovulation, perhaps compensating for addi- maternal condition and optimize lifetime reproductive
tional energetic expenses of hormone production output (Ellison, 2003b). With longer interbirth inter-
(Johnson et al., 1994). Such evidence points to the fact vals, women can improve their nutritional status
that some additional energy beyond regular mainten- before the next energy drain caused by pregnancy and
ance needs is required to support regular menstrual lactation. Negative energy balance is a transient state,
function (Strassmann, 1996), although these costs are often occurring just seasonally, and quickly changing
negligible in comparison with the energetic demands when food availability improves or workload lightens.
associated with pregnancy and lactation. Ellison0 s hypothesis elegantly explains why reproduc-
Frisch (1984) proposed that, due to high the ener- tive suppression is adaptive in women with a negative
getic costs of pregnancy and lactation, ovarian func- energy balance. However, suppression occurring in
tion should respond in an on/off manner to the body fat response to high levels of physical activity in women
stores. A woman with body fat insufficient to support with a neutral or positive energy balance (i.e., not
the energetic costs of pregnancy and lactation should losing or gaining body weight) requires additional
be unable to conceive. However, while fat stores may explanation.
indeed be necessary to support the energetic costs of The “constrained downregulation” hypothesis pro-
milk production (McNamara, 1995), such stores are posed that intense workload compromises a woman0 s
insufficient to support the energetic costs rendered by ability to allocate sufficient energy to reproduce
both pregnancy and lactation. (Jasienska, 2001, 2003). Women who, as a result of
Data demonstrating that women in developing increased physical activity, remain in a state of high-
countries often have very low fat reserves (Lawrence energy flux (high-energy expenditure compensated by
et al., 1987; Little et al., 1992; Panter-Brick, 1996) led to high-energy intake), may have an impaired ability to
the hypothesis that, in the developing world, the func- downregulate their own metabolism when faced with
tion of fat stores is to serve as an emergency resource. increasing energetic needs of pregnancy and lactation.
Maternal fat stores may become useful when environ- Lowered basal metabolism serves as one mechanism
mental conditions decline, but they cannot be used allowing women from traditional subsistence popula-
to steadily support milk production (Prentice and tions to allocate more energy to reproduction (Poppitt
Prentice, 1990; Lunn, 1994). Even in well-nourished et al., 1993, 1994; Sjodin et al., 1996). On the other
Western women, body fat stores used to support just hand, increased basal metabolism is frequently obser-
half of lactation costs would last not longer than ved in individuals who exhibit increased physical acti-
11 months. In poorly nourished Gambian women, fat vity (Sjodin et al., 1996). It is possible that these
reserves used for this function would last for only hard-working women with elevated basal metabolism
4 months (Prentice and Prentice, 1990; Lunn, 1994). have constrained ability to redirect energy for repro-
It should be stressed that women are capable of ductive processes. In this case, temporary suppression
supporting a reproductive episode on a limited energy of ovarian function may be adaptive even in individuals
supply, but this does entail substantial long-term costs. who are still sustaining positive energy balance.
Reproduction in women in poor energetic conditions is
often associated with diminished reproductive out-
comes, reflected by poor newborn health conditions THE HOURGLASS FIGURE: RELATIONSHIPS
(Lechtig et al., 1975; Roberts et al., 1982; Kusin et al., BETWEEN BODY SHAPE AND
1992; Siniarska, 1992; Pike, 2000). These children are, HORMONE LEVELS
as adults, at increased risk of several metabolic
diseases (Barker, 1994; Gluckman and Hanson, 2004; According to human evolutionary psychology, physical
Gluckman et al., 2005a). Reproduction during poor characteristics like breast size and waist-to-hip ratio
energetic conditions also worsens maternal nutritional (WHR) are used by human males to assess female
status (“the maternal depletion syndrome”) (Merchant attractiveness (Singh, 1993; Tovee et al., 1999). Males
may pay attention to these features because they may (Tuschen-Caffier et al., 1999), but these results cannot
serve as cues to fecundity and health. However, only a be used to suggest that psychological stress was the
few studies have reported significant relationships primary factor causing infertility.
between a low WHR (narrow waist, wider hips) or “Psychological stress” is a broad concept, and stu-
large breast size and increased fecundity. In addition, dies use various ways to qualify and quantify psycho-
in most such studies, women with high WHR were also logical stress, focusing on “stressors,” “perceived
obese (Evans et al., 1983; Moran et al., 1999), or were stress,” or physiological “stress responses.” Cortisol
patients of fertility clinics (Zaadstra et al., 1993). Low levels are often used as markers of psychological stress,
fecundity in such women may be the direct effect of and while they indeed become elevated in response to
obesity and not a high WHR. stressful stimuli, cortisol is also elevated in response
One study investigated the relationship between to energetic stress. Mobilization of energy due to, for
body shape and fecundity in nonobese, fecund women example, physical activity, infection, or low ambient
(Jasienska et al., 2004). Women with a higher breast- temperature is associated with high levels of cortisol
to-underbreast ratio (larger breasts) and women with a (Hackney and Viru, 1999). Therefore, a relationship
relatively low waist-to-hip ratio (narrower waists) had between cortisol levels and ovarian hormones cannot
significantly higher fecundity as assessed by estradiol be used as the evidence that psychological stress sup-
and progesterone levels. Even more interesting was the presses ovarian function. To complicate things further,
finding that women who were characterized by both a psychological stress and energetic stress often coin-
narrow waist and large breasts had 26% higher mean cide. For example, in traditional agricultural popula-
estradiol and 37% higher mean mid-cycle estradiol tions, famine may lead to both weight loss and high
levels than women with other combinations of body anxiety levels.
shape variables (i.e., low WHR with small breasts and A potential impact of moderate, acute psycho-
high WHR with either large or small breasts). In this logical stress on levels of ovarian steroid hormones
study, breast sizes and WHR were large or small, in a was addressed in a study of United States college
relative sense; population mean values were used as women taking the Medical College Admission Test
criteria for categorizing women into groups of large (MCAT) (Ellison et al., 2007). Women who took the
or small sizes. Therefore, a relationship between body MCAT had significantly higher scores of anxiety during
shape and reproductive potential can be detected even the months preceding the MCAT exams than several
within a group of otherwise “average” women. months after the exams. During the exam period,
their anxiety was also higher than in women from
the control group. Despite the differences in levels of
PSYCHOLOGICAL STRESS AND FECUNDITY self-reported anxiety reported by women, no statistic-
ally significant differences were observed in the levels
We know that infertility often causes psychological of cortisol, estradiol, or progesterone. In addition,
stress, but there is limited evidence that psychological the relationship between chronic anxiety levels and
stress causes infertility (Campagne, 2006). Many ovarian function was examined in women 27–41 years
women with fertility problems report high levels of of age. There was no statistically significant relation-
psychological stress, and these results are often inter- ship between chronic anxiety and levels of either corti-
preted as evidence that psychological stress influences sol or ovarian hormones. In total, the study did not
fecundity. Despite great interest in the potential impact identify any suppressive effects of moderate anxiety,
of psychological stress on the ability to conceive, or on either acute or chronic, on ovarian function.
the risk of early pregnancy loss (Domar et al., 2000; In general, it is too early to conclude if psycho-
Smeenk et al., 2001; Boivin, 2003; Cwikel et al., 2004; logical stress has a suppressive effect on ovarian
Anderheim et al., 2005; Nepomnaschy et al., 2006), it is function. Carefully controlled studies on the effects of
not clear if moderate psychological stress may indeed energetic stress on ovarian function in women from
have such detrimental effects. traditional, non-Western populations may help resolve
Studies investigating relationships between psy- this problem.
chological stress and fertility in women are plagued
by several methodological problems (Ellison et al.,
2007). Frequently, stress levels of women at fertility IS VARIATION IN HORMONE LEVELS
clinics are compared to stress levels in women who EXPLAINED BY GENETIC VARIATION?
do not exhibit fertility problems (Harrison et al.,
1986; Domar et al., 1990). It is not surprising if the Levels of ovarian hormones within and between popu-
former group experiences more severe psychological lations may be influenced by genetic polymorphisms,
stress. Cognitive-behavioral therapy may improve and there are several candidate genes. For example,
some aspects of fertility in otherwise infertile couples some studies suggest that polymorphisms of the
estrogen receptor genes are related to variation in (Garcia-Closas et al., 2002; Travis et al., 2004) which
levels of androgens in premenopausal women also did not identify significant differences in estradiol
(Westberg et al., 2001) and variation in levels of levels among CYP17 genotypes, used a single blood
estradiol in postmenopausal women (Peter et al., sample per woman for hormone measurements.
2008). However, a large multiethnic study has found Only two studies have controlled for within-cycle
only weak (explaining < 4% of variation) and inconsis- variability in estradiol levels by measuring hormones
tent associations between receptor genetic polymor- levels via multiple samples. Over a 2-year period, Lurie
phism and estradiol levels (Sowers et al., 2006). et al. (2005) sampled women, on average, at 4.4 time
Genetic variants of CYP17, CYP19, CYPA1A, and points and did not identify any significant relation-
CYPB1B are involved in the steroid metabolic pathway ships between estradiol levels and CYP17 genotype. In
and code for enzymes involved in steroid production contrast, Jasienska et al. (2006a) measured ovarian
and metabolism. These genetic variants can therefore hormone levels in saliva samples collected daily across
influence levels of circulating steroid hormones. The an entire menstrual cycle. In this case, variation in
most intensely studied of all genes involved in steroid estradiol levels was partially explained by polymorph-
metabolism are CYP19 and CYP17. ism at the CYP17 locus: women with A2/A2 genotypes
CYP19 encodes aromatase, a key enzyme in the had 54% higher mean estradiol levels than women with
synthesis of estrogens. Several studies have docu- A1/A1 genotypes, and 37% higher mean estradiol levels
mented a relationship between polymorphism of this than women who had only one A2 allele. Heterozygous
gene and estrogen levels in postmenopausal women A1/A2 women had 13% higher estradiol levels than
(Tworoger et al., 2004; Haiman et al., 2007; Peter homozygous A1/A1 women. Levels of estradiol during
et al., 2008), but not in the menstrual cycles of younger the preovulatory day were 72% higher in A2/A2 com-
women (Garcia-Closas et al., 2002). CYP17 encodes pared to A1/A1, and 52% higher compared to A1/A2.
cytochrome P450c17a, which mediates activities of While variation in levels of hormones in response
the enzymes 17a-hydroxylase and 17,20-lyase, both energetic factors, such as energy balance or energy
involved in the biosynthesis of estrogen (Small et al., expenditure, can be explained as adaptive, the exist-
2005). A single nucleotide polymorphism in the ence of genetic variation at the loci responsible for
50 -untranslated region of CYP17 is relatively common, hormone production is not immediately clear. Since
and presence of the A2 allele is thought to increase high levels of hormones are important determinants
transcription rates. In other words, having a simple of female fecundity, one would expect a strong and
mutation in CYP17 (e.g., having the A2 allele as part consistent selective pressure promoting the alleles
of the CYP17 genotype) increases enzyme production encoding high levels of reproductive hormones. These
rates needed for the synthesis of estrogens. alleles should be most prevalent in all contemporary
The relationship between CYP17 polymorphism and populations. Instead, in all studied populations there
estradiol levels in premenopausal women has been the is a considerable polymorphism in genes involved in
focus of several studies (Feigelson et al., 1998; Garcia- steroid production and metabolism. Why are the low-
Closas et al., 2002; Travis et al., 2004; Hong et al., 2004; steroid alleles present in modern populations at all?
Lurie et al., 2005; Small et al., 2005), although results Females with alleles that code for high production
are inconsistent. Estradiol levels measured around day of reproductive hormones could have a clear selective
11 of the menstrual cycle have been reported to be 11% advantage over females with allelic variants coding for
and 57% higher among women with genotypes A1/A2 lower steroid levels. However, those with high-level
and A2/A2, respectively, compared to A1/A1 women alleles could potentially exhibit lower lifetime fitness
(Feigelson et al., 1998). Estradiol levels during the luteal compared to other females. While estrogens are in
phase, around day 22 of the cycle, were reported to be general beneficial for fecundity and health in women,
7% and 28% higher for women with A1/A2 and A2/A2, high estrogen levels are also responsible for increased
respectively. Women with the A2/A2 genotype had 42% risk of hormone-dependent cancers, including breast
(and heterozygotes A1/A2 19%) higher estradiol than the cancer (Pike et al., 1983, 1993; Bernstein and Ross,
A1/A1 homozygotes, but this was true only for women 1993). Therefore, women with high levels of estradiol
with BMI values not greater than 25 kg/m2 (Small et al., would have the advantage of having higher potential
2005). It is important to note that both of these studies fertility, but at the risk of dying from reproductive
were based on only one or two estradiol values meas- cancers. Reproductive cancers are, however, most
ured per woman. prevalent in postmenopausal women.
Another study of premenopausal women did not An alternative explanation is that low-level alleles
identify any differences in estradiol levels among are simply sufficient for normal physiological func-
CYP17 genotypes, but rather documented significant tions, but that lifestyle changes associated with the
differences in dehydroepiandrosterone levels (Hong introduction of agriculture led to the consumption of
et al., 2004). This study, in addition to two others larger quantities of food which contain high
concentrations of phytoestrogens. These chemicals observational studies allow us to only conclude that
bind to estrogen receptors and influence activity of two variables are correlated. For example, causality
enzymes involved in the steroid metabolism (Kuiper cannot be determined between the correlation of
et al., 1998; Xu et al., 1998). When consumed in large WHR ratio and estrogen levels. Estrogen influences
quantities, these chemicals may reduce levels of the pattern of fat distribution so that women with
endogenous estrogens (Kapiszewska et al., 2006; Xu higher estrogen levels may have higher fat deposition
et al., 1998). Phytoestrogens exhibit much more potent in the hip region, or lower fat deposition in the waist
estrogen receptor binding abilities when diet is rich in region, or both. At the same time, body fat influences
carbohydrates, a common feature in agricultural popu- estrogen levels, and women with high abdominal
lations (Setchell and Cassidy, 1999). fat may have reduced levels of estradiol. Causality
In ancestral populations that lacked high consump- in this example is likely complex and bidirectional.
tion rates of phytoestrogens, the levels of hormones The relationship between physical activity, ovarian
coded by low-levels alleles could have been optimal function, and estrogen levels seems to be much more
for ovarian function, ensuring sufficiently high prob- straightforward.
ability of conception. But because increased phytoes-
trogen consumption may cause lower fecundity in
women, consuming large quantities of phytoestrogens ARE HIGH LEVELS OF HORMONES IN
after the spread of agriculture may have placed a WESTERN WOMEN A PHYSIOLOGICAL NORM?
selective advantage on high-level genotypes.
Medical sciences have assumed that urban women
from industrialized countries have physiology operat-
HORMONE LEVELS AND
ing at optimal levels. Therefore, high levels of ovarian
GENE–ENVIRONMENT INTERACTIONS
hormones in menstrual cycles are considered a physio-
logical norm. Lower hormone levels in women from
In healthy women of comparable ages, variation in
non-Western populations are not discussed much in
hormone levels can be explained, to a large extent, by
medical literature. Many physicians have and still do
variation in energetic factors, which in turn are related
consider low ovarian hormonal levels in these women
to environmental conditions. Energy availability to a
as pathological. However, as pointed out by Ellison
developing fetus, to a growing girl, and to an adult
(2003b), hormone levels in Western women actually
woman influences the levels of hormones produced
appear to be abnormally high. Abundant availability
during the menstrual cycles. But what about gene–
of energy during fetal and childhood development
environment interactions? Do women with genetically
and during adult life contributes to the presence of
influenced low levels of hormones have comparable
high levels of ovarian hormones. Such energetic condi-
responses to environmental energetic factors as do
tions were unlikely features throughout the majority of
women with genetically influenced high levels? Would
human evolution.
physical exercise of exactly the same duration and
In Western populations, women also have high
intensity have the same effect on women of different
numbers of cycles during their lives (Strassmann,
genotypes? No studies have so far addressed these
1997; Eaton and Eaton III, 1999). Early age at
questions. If the suppression of reproductive function
menarche and late age at menopause expand the
is an adaptive response to low availability of metabolic
range of years during which cycles occur. With fewer
energy, should similar responses be observed in all
pregnancies, a woman spends more time cycling.
women, regardless of whether they are genetically low
With fewer pregnancies, a woman also spends less
or high hormone “producers”?
time breast-feeding. Even while breast-feeding, a
Furthermore, as suggested before, genetic variation
woman may resume her cycles early, because of
in hormone levels may be a relatively new evolutionary
infrequent nursing episodes and good maternal
phenomenon, appearing after the origin of agriculture.
nutritional status (Valeggia and Ellison, 2004). Com-
If so, it may be that an inadequate amount of time has
bined, this may expose her to higher lifetime levels of
elapsed for different genotype-specific responses to
estrogens.
environmental challenges to have evolved.
In women, many aspects of health and disease
are estrogen-dependent, including cardiovascular
DETERMINANTS OR MERELY CORRELATES function, bone density, psychological well-being, and
OF HORMONE LEVELS? reproductive cancers (Key and Pike, 1988; Barrett-
Conor and Bush, 1991; Pike et al., 1993; Nguyen
While some of the factors described here clearly influ- et al., 1995; Jasienska et al., 2000; Jasienska and Thune,
ence levels of hormones, others just show correlations 2001a, 2001b; Jasienska, 2002). In premenopausal
with hormonal levels. Results of cross-sectional, women of reproductive age, those with higher
estrogen levels may also be in better health, since estro- Barnett, J. B., Woods, M. N., Rosner, B., et al. (2002). Waist-
gen at normal physiological levels can be immunosti- to-hip ratio, body mass index and sex hormone levels
mulatory (Kovacs et al., 2002; Jacobson and Ansari, associated with breast cancer risk in premenopausal Cau-
2004). However, women who have high estrogen levels casian women. Journal of Medical Sciences, 2, 170–176.
Barrett-Conor, E. and Bush, T. L. (1991). Estrogen and
during their reproductive years may suffer detrimental
coronary heart disease in women. Journal of the American
health effects in their postmenopausal years. High
Medical Association, 265, 1861–1867.
lifetime levels of reproductive hormones are related to
Becker, A. E., Grinspoon, S. K., Klibanski, A., et al. (1999).
increased risk of hormone-dependent cancers (Key and
Current concepts – eating disorders. New England Journal
Pike, 1988; Pike et al., 1993; Jasienska et al., 2000; of Medicine, 340, 1092–1098.
Jasienska and Thune, 2001a, 2001b;Yue et al., 2003). Benefice, E., Simondon, K. and Malina, R. M. (1996). Phys-
The knowledge of factors capable of influencing the ical activity patterns and anthropometric changes in
levels of hormones is crucial for understanding Senegalese women observed over a complete seasonal
determinants of health and disease, and for designing cycle. American Journal of Human Biology, 8, 251–261.
effective programs of disease prevention for women. Bernstein, L. and Ross, R. K. (1993). Endogenous hormones
and breast cancer risk. Epidemiological Reviews, 15, 48–65.
Bernstein, L., Ross, R. K., Lobo, R. A., et al. (1987). The
DISCUSSION POINTS effects of moderate physical activity on menstrual cycle
patterns in adolescence: implications for breast cancer
24. What factors influence levels of ovarian steroid prevention. British Journal of Cancer, 55, 681–685.
hormones in adult women? Bisdee, J., James, W. and Shaw, M. (1989). Changes in
25. What is the relationship between conditions energy expenditure during the menstrual cycle. British
Journal of Nutrition, 61, 187–199.
experienced during fetal development and
Bledsoe, R. E., O0 Rourke, M. T. and Ellison, P. T. (1990).
ovarian function during adulthood?
Characterization of progesterone profiles of recreational
26. Reproduction in women is energetically costly.
runners. American Journal of Physical Anthropology,
Would you expect a linear, positive relationship 81 (abstract), 195–196.
between energy stored as body fat and levels of Boivin, J. (2003). A review of psychosocial interventions in
ovarian hormones in women? Why, or why not? infertility. Social Science and Medicine, 57, 2325–2341.
27. Reduced levels of ovarian steroid hormones lead Broocks, A., Pirke, K. M., Schweiger, U., et al. (1990). Cyclic
to reduced ability of conception, yet a hypothesis ovarian function in recreational athletes. Journal of
suggests that “ovarian suppression” in response to Applied Physiology, 68, 2083–2086.
physical activity or weight loss can be adaptive Bruning, P. F., Bonfrer, J. M. G., Hart, A. A. M., et al. (1992).
(i.e., is evolutionarily advantageous). Can you Body measurements, estrogen availability and the risk of
explain this apparent paradox? human breast cancer: a case-control study. International
28. Are high levels of estrogen beneficial for women? Journal of Cancer, 51, 14–19.
Bullen, B. A., Skrinar, G. S., Beitins, I. Z., et al. (1985).
Induction of menstrual disorders by strenuous exercise
in untrained women. New England Journal of Medicine,
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20 Pregnancy and Lactation
Ivy L. Pike and Lauren A. Milligan
In this chapter, we draw on life history theory to create over an individual’s lifetime rather than fitness at one
a comparative framework for exploring pregnancy and point in time or the maximization of one particular life
lactation as coevolved elements of the primate repro- history trait (Alberts and Altmann, 2003). Using this
ductive strategy, broadly defined. We draw on the theoretical framework, a species’ reproductive strategy
physiological evidence to create a picture of how preg- is predicted to maximize the mother’s fitness, or repro-
nancy and lactation represent a highly integrative ductive success, over her lifetime. However, pregnancy
reproductive strategy. Life history theory offers several and lactation also affect the fitness of the offspring.
advantages for understanding this integrative primate The offspring is predicted to maximize its own lifetime
reproductive strategy. Firstly, by comparing life history fitness, which may or may not be at odds with that of
characteristics across nonhuman and human primates the mother (Trivers, 1974). Given the importance of
we can examine benefits and costs to this energetically maternal transfer of nutrients during gestation and
expensive strategy and how natural selection may have that milk is the only source of nutrition for neonates
tailored aspects of the larger strategy toward more and developing infants, selection is expected to favor a
species specific ends. Secondly, life history theory strategy that balances the interests of maternal and
emphasizes trade-offs between survival and current offspring survival. The pattern and rate of growth and
reproduction, current and future reproduction, and development of the offspring, established in utero,
number, size, and sex of offspring among many others requires the production of sufficient milk quality and
(Stearns, 1992). We take the position that these trade- quantity. In turn, maternal energy balance and body
offs must be examined from the dual vantage point size determine the mother’s ability to provide the
of the mother and the fetus/infant since the two will necessary resources for growth and development
not always have completely overlapping interests. during lactation (Lee, 1999).
The chapter unfolds across four sections. In the first Life history traits are products of natural selection
section, we explore the primate reproductive strategy and therefore a species’ life history strategy is intim-
by comparing life history parameters across broad ately tied to that species’ evolutionary history. Natural
phylogenetic groupings, making note of similarities selection elaborates, rather than innovates, leading to
and differences. The next section examines gestation similarities in life history traits among closely related
from the perspective of maternal constraint, maternal species. Across the mammalian class considerable
investment in reproduction, and physiological mechan- physiological similarities exist with the important
isms that might shift the cost of any given pregnancy. exception of reproduction (Smith, 2007). For example,
Mechanisms that might enhance fetal survival and offer variation on how placental mammals proceed to par-
developmental cues are also explored. In the lactation turition varies widely (Smith, 2007). Only anthropoid
section, lactation is viewed as a highly conserved part primates produce corticotrophin-releasing hormone
of the reproductive strategy but with considerable bio- (CRH), a neuropeptide found in amphibians and
logical and behavioral flexibility. We conclude by argu- mammals (Denver, 1997), in the placenta (Smith et al.,
ing that an evolutionary approach that draws on both 1999; Power and Schulkin, 2006). Also, only gorillas,
biocultural and life span perspectives to examine preg- chimps, and humans experience increasing levels of
nancy and lactation has important policy implications. CRH across pregnancy, apparently playing a role in
timing parturition (Smith et al., 1999; Bowman et al.,
THE PRIMATE REPRODUCTIVE STRATEGY: 2001; Power et al., 2006). The wide range in age at
SITUATING HUMANS IN A BROADER CONTEXT weaning among primates (e.g., Ross, 2003) indicates
that the duration of lactation has been modified by
Life history theory asserts that life history traits have selection over the course of primate evolution. Such
evolved as a suite, and the target of selection is fitness data suggest different components of pregnancy and
338
Pregnancy and Lactation 339
lactation also would be likely targets of selection over mammalian mothers still need to increase their non-
the course of primate evolution. However, similarity reproductive energy intake above normal levels to sus-
of life history traits within genera, families, and even tain infant growth (Lee, 1996). For example, baboon
superfamilies indicate a phylogenetic ordering to this mothers are estimated to require 1.5 times and human
variation. A species’ reproductive strategy therefore females 1.3 times their normal energy intake (non-
may carry phylogenetic baggage, both in regard to pregnant and nonlactating) (Lee, 1996, 1999).
the genetic makeup of inherited trait and the range of The lactation strategy can be divided into four,
variation (phenotypic plasticity) in this expression. interrelated traits: the composition of the milk pro-
Like other life history traits, the primate reproduct- duced, the volume of milk produced, the frequency at
ive strategy also may be an adaptive response to which the mother feeds the infant throughout the day,
ecological variation (Morbeck, 1997a, 1997b; Hill and and the total duration of lactation per reproductive
Kaplan, 1999; Kaplan et al., 2000). Morbeck (1997b) cycle. All these elements must work together to deliver
argues that external factors such as climate, the quality the necessary nutrients and tactile stimulation to the
and quantity of available food, disease ecology, and infant for its growth and development without irrevers-
group structure can affect the timing, duration, and ibly compromising maternal health. The duration of
energetic effort of an individual’s life history. As an lactation is considered a life history trait of the species;
example, mechanisms that modify fecundity and con- a trait that exhibits considerable flexibility in timing
ception have been documented and suggest the ability within and across species. Milk composition, volume
to delay conception when conditions are poor (Wood, of milk produced, and nursing frequency can also
1994; Ellison, 2001, 2005). Primate mothers may be modeled as life history traits. As such, each of the
choose to lengthen lactation if ecological conditions four components of the lactation strategy is subject
are poor, or shorten lactation when conditions are to natural selection, as each interacts with the environ-
good (Lee, 1996). The extent to which they are able to ment and other life history traits to maximize the
do this is part of their evolutionary history, however, fitness of the individual.
and the degree of plasticity is itself a product of natural
selection (Morbeck, 1997a).
Gestation represents a considerable energetic FAT STORAGE, GESTATION, AND
investment but the daily costs of fetal growth are lower LACTATION – IS IT ALL ABOUT THE BRAIN?
than might be expected among primates when exam-
ined across mammals (Dufour and Sauther, 2002; The human brain is approximately one-third lipid, all
Ulijaszek, 2002) and this may be achieved in part by of which must be supplied to fetuses and young infants
having longer gestational durations (Martin, 1996). by the mother in utero and in milk, respectively.
When compared to great apes, humans invest more A relatively larger brain with a longer period of post-
heavily in fetal tissue, with fetal body fat comprising natal growth may have been linked to the selection of
approximately 61% of the total cost of pregnancy an increased ability in human females to store energy
(Dufour and Sauther, 2002; Ulijaszek, 2002). There is and later mobilize this stored energy for lactation. The
considerable flexibility in meeting the energetic human brain has “obligatory and inflexible require-
demands of gestation (Dufour and Sauther, 2002), with ments” (Kuzawa, 1998, citing Armstrong, 1983) across
examples of lower basal metabolic costs for females a range of nutrients, with some less “inflexible” than
who experience marginally adequate nutritional levels others. Development of significant fat stores may be
(Durnin, 1987; Prentice and Goldberg, 2000). Ultimately, a physiologically linked adaptation to changes in
fetal growth and body composition reflect a compromise rate and pattern of brain growth (Ulijaszek, 2002).
between maternal and fetal interests (Wells, 2003). Although large fat stores are found in many female
Lactation is the most energetically expensive com- mammals, including nonhuman primates, human
ponent of a mammalian female’s reproductive strategy female fat stores are argued to be relatively larger than
(Pond 1984, 1997; Gittleman and Thompson, 1988), (Dufour and Sauther, 2002) and different from (Pond,
with energetic costs and micronutrient requirements 1997) the female primate pattern. Further, the degree
shifting to reflect infant growth and development of difference in fat mass between males and females is
trajectories (Picciano, 2003). Like gestation, the cost greater in humans than nonhuman primates. While
of lactation is argued to be related to maternal body human males are heavier than females, females are
size and to the evolutionary history of the species fatter, with 34% more fat mass on average than males
(Martin and MacLarnon, 1985). Lee (1996) argues that (Wells, 2006). Wells (2006) argues that the greater fat
the energy cost of lactation is inescapable; mothers mass of human females relative to human males and to
must convert maternal nutrients or body reserves to nonhuman primate females indicates the importance
milk. Although the conversion of maternal stores or of reproductive energetics in human evolution. Specif-
dietary intake to lactation is relatively efficient, most ically, he proposes that the evolution of fatness in
340 Ivy L. Pike and Lauren A. Milligan
human females is at least partly the result of From the maternal perspective, reproduction rep-
encephalization. resents a balance of shorter- and longer-term trade-offs
Dufour and Sauther (2002) report on four non- (Ellison, 2001, 2005). Given the energetic cost of preg-
Western human populations, in which females have nancy, maternal investment in any given pregnancy
greater than 20% body fat. There is little comparative only makes sense if the demands do not threaten sur-
data on nonhuman apes, but data on captive lowland vival. If maternal condition, defined as the adequacy of
gorillas (Zihlman and McFarland, 2000) show that one her growth, health, and nutritional experience across
captive female gorilla had the potential to store similar the life span, is marginal then investing in an individ-
amounts of body fat. It is unknown if wild living apes ual pregnancy is weighed against future reproductive
are capable of maintaining the percent body fat of opportunity. If opportunity is low, for example due to
human females. Such data would be invaluable to deter- older maternal age, then investing in gestation now
mine if adult female fat storage is indeed a unique- may be worth the risk and may benefit overall repro-
derived human adaptation to support brain growth. ductive success. If future reproductive opportunity is
Another possibility is that the cost of growing a high, delaying conception until maternal condition
larger brain was not met through alterations to the or environmental circumstances improve offers a
reproductive strategy at all. Modern human infants reasonable trade-off. Strategies look different if mater-
have a precocious condition of adipose development nal condition is poor as a result of an acute insult
at birth (Kuzawa, 1998; Ulijaszek, 2002) and are the versus chronic energetic deficiency across the life span.
fattest species on record at birth (Kuzawa, 1998). In the presence of chronic stress, waiting for maternal
While variation in human fatness at birth exists across condition to improve may be a higher risk strategy.
a range of pregnancy-related circumstances, including Instead, relying on mechanisms that might limit the
maternal weight gain and fat stores during pregnancy, cost of individual pregnancies may be a more viable
fatness is argued to be an adaptation to the higher lipid strategy (Prentice and Goldberg, 2000; Pike, 2005).
needs of newborns for rapid brain growth during the Several different mechanisms have been proposed
first year of life (Kuzawa, 1998; Ulijaszek, 2002). Like for lowering the energetic cost of pregnancy. One well-
maternal depot fat stores, infant fat stores (deposited documented physiological mechanism is to lower basal
primarily during the third trimester) would act as a metabolic rate during gestation, particularly via reduc-
buffer against disruptions in energy transfer during tion in diet-induced thermogenesis (Durnin, 1987;
lactation (Kuzawa, 1998). As reviewed by Kuzawa Dufour et al.,1999). Another widely examined mechan-
(1998), this hypothesis is indirectly supported by data. ism is to reduce energy expenditure, particularly
Without comparative data from nonhuman primates, during the third trimester when the energy demands
it is not possible to say whether this is a unique human of even basic movements are higher ( Lawrence et al.,
adaptation or a nonadaptive consequence of other 1985; Lawrence and Whitehead, 1988; Panter-Brick,
ontogenetic changes (such as increased fat storage by 1989, 1992; Dufour et al., 1999). Although humans
the mother). exhibit slower fetal growth across longer gestations
when compared to other nonhuman primates (Dufour
and Sauther, 2002; Ulijaszek, 2002), several lines
of research suggest limiting fetal growth may incur
PREGNANCY energetic savings. Drawing on studies of genomic
imprinting and Trivers’s (1974) ideas regarding
Gestation long has been considered a critical selective parent–offspring conflict, Haig (1993) suggests there
point in reproductive success. In addition to low may be maternally derived fetal genes that limit
fecundability (Wood, 1994), fetal loss during the first fetal growth, with predictions that paternally derived
4 weeks of gestation are estimated at 40–50% (Wood, genes might encourage fetal growth. Recent evidence
1994), with fetal deaths across pregnancy representing suggests that maternal neurohormonal cues that signal
a considerable modifier of birth intervals and thus a poor or insufficient intrauterine environment can
total reproductive potential (Wood, 1994; Holman accelerate fetal developmental trajectories (McLean
and Wood, 2001). Methodological constraints focused et al., 1995; Pike, 2005), creating a “thriftier pheno-
attention on pregnancy outcomes, such as gestational type” (Hales and Barker, 2001). A shortened gesta-
duration and weight and length at birth, as proxies for tional duration once the fetus is viable may offer
the adequacy of the fetal experience. Yet more recent important energetic savings for the mother by limiting
advances in physiology, genetics, endocrinology, and the higher costs of fetal fat deposition and the active
gestational age assessments, have provided opportun- transfer of maternal nutrients (Peacock, 1991). Such
ities to refine our understanding of the selective strategies may limit the cost of an individual preg-
pressures and evolutionary relationships between the nancy but come with important risks for perinatal
maternal–fetal unit. and longer-term survival for the infant.
The developmental experiences of the mother, specific fetal developmental trajectories (Wadhwa et al.,
strongly patterned by her environmental context, also 2001). Signals of an insufficient environment, in turn,
set important constraints on fetal growth and develop- trigger a cascade of facultative responses in the fetus.
ment. If a mother experienced intrauterine growth These responses include an acceleration of fetal organ
restriction as a fetus, she is more likely to mature maturation (Dodic et al., 1999; McGrath and Smith,
at an earlier age (Adair, 2001), is smaller overall in size 2001), maximization of blood flow to the fetus (McLean
at maturity (Simondon et al., 1998), and may have a et al., 1995; Smith et al., 2002), asymmetrical growth
smaller pelvic size, and smaller uterus and ovaries resulting from preferential allocation of resources to
(Ibanez et al., 2000, 2006). Such responses to a poor important growth centers (Fowden, 2001), and when
intrauterine nutritional environment may place limits extreme threats are present then a shift in the endocrine
on adequate fetal growth. There is additional evidence cascade leading to parturition may occur allowing early
that chronic psychosocial stress across a mother’s life expulsion from the stressful environment (McLean
span alters her developmental trajectory. In contexts of et al., 1995). The full range of potential responses and
high psychosocial stress an earlier age at menarche has some of the precise mechanisms remain vague but
been documented (Ellis and Garber, 2000; Coall and some intriguing pathways have been illuminated.
Chisholm, 2003). These responses may limit the overall Additional evidence for the importance of environ-
cost of a pregnancy and thus offer increased opportun- mental cues for fetal development comes from links
ity for reproduction but come with intergenerational between placental CRH and the role it plays in fetal
consequences that have important long-term public neurodevelopment (Wadhwa et al., 2001). The central
health implications. nervous system develops over 11–12 years but the fetal
From the fetal perspective, one body of literature, period remains critical to normal development (Rodier
in particular, has generated considerable interest in et al., 1994). The sensitivity of neurotransmitters in the
possible mechanisms that allow fetal adaptations to central nervous system are set during critical periods
a poor or insufficient maternal environment. This of development and affect the organisms response
research suggests fetal growth restriction, combined to all subsequent experiences (Rodier et al., 1994).
with the modifying effects of early childhood growth Environmental perturbations in utero and the subse-
and development, may result in permanent alterations quent response in the central nervous system are
in organ and metabolic function that place individuals poorly understood (Wadhwa et al., 2002). However,
at greater risk for adult-onset diseases (Barker et al., experimental studies using a series of vibroacoustic
1993) (see Chapter 30 of this volume for more details). stimuli over the fetal head suggest the fetus can detect
One closely related body of literature suggests mater- and habituate to external stimuli by the third trimester
nal stress, as measured by elevated glucocorticoids and (Sandman et al., 1997). From the same study, mother–
CRH, relays information of a poor or insufficient fetal fetus pairs with elevated CRH levels were tested using
environment across the placenta to the fetus, initiating the same stimuli and measures of responsiveness (fetal
a hormonal cascade that accelerates fetal maturation heart rate). The researchers found a blunted response
and results in preterm delivery (defined as <37 weeks to novel external stimuli in fetuses with high
from last menstrual period). Such research suggests CRH levels (Sandman et al., 1997). If subtly stressful
developmental trade-offs that respond to signals of a stimuli impact fetal responsiveness there is consider-
poor or insufficient environment, resulting in enhanced able evidence that maternal anxiety and experiences of
short-term survival with long-term consequences and traumatic events also have lasting effects on the fetus
risks. For example, in addition to the many conse- and infant (Brouwers et al., 2001; Tagle et al.; 2007).
quences of preterm delivery such as increased risk for Thus, the prenatal environment appears to play an
mortality and increased vulnerability to respiratory important role in appraisal, responsiveness, and habitu-
diseases, fetal exposure to elevated maternal stress ation in postnatal life (Wadhwa et al.; 2002).
hormones appears to increase reactivity to stress in The maternal–fetal unit simultaneously experi-
early childhood and even into adulthood (Brouwers ences competing and overlapping interests. Wells
et al., 2001; Weinstock, 2001). (2003) suggests fetal size and body composition at
The influence of environment on development has birth reflect a compromise between maternal and fetal
been appreciated since the earliest studies of growth strategies. Constrained fetal growth and altered metab-
(Tanner, 1998). While research on pregnancy out- olism may represent a series of facultative responses
comes highlights the importance of the maternal envir- manipulated by the mother in response to the quality
onment on fetal growth, more recent research suggests of the environment (Adair, 2001; Wells, 2003). Lampl
the embryo/fetus monitors information about the (2005), however, reviews the evidence for maternal
adequacy of the intrauterine environment (Wadhwa versus fetal adaptations to an insufficient environment
et al., 1993, 2001; McLean et al., 1995). Such information and concludes the opposite, that the fetus controls
may serve as necessary cues that guide environmentally developmental responses to an insufficient environment.
In either case, selective pressure to meet competing of abundance (Oftedal, 2000; Pond, 1984). The demands
evolutionary demands between mother and fetus of lactation are met in a variety of ways depending
seems likely and highlights the importance of examin- on factors such as the condition of the environment,
ing reproduction from a maternal/offspring perspective. the species’ ontogenetic priorities, and genetically pro-
As further evidence of the physiological interde- grammed physiological traits, such as fat storage and
pendency between mother and offspring, parturition metabolism (Oftedal, 1984, 2000).
reflects a transition from active transport of nutrients Parent–offspring conflict theory (Trivers, 1974)
across the placenta to more passive transport via predicts that mothers and infants should have behav-
breastmilk. The process of lactogenesis begins in ioral conflicts over the allocation of parental invest-
mid-pregnancy as mammary glands differentiate and ment, such as length of lactation. Much empirical
prepare for secretion (Neville, 2001; Neville et al., work has been done on the issue of weaning conflict,
2001). The successful production of milk, defined as that is, the conflict between mother and infant on the
lactogenesis stage II, occurs at approximately day four scheduling of when the infant must become nutrition-
postpartum and is mediated by the neurophysiological ally independent of the mother (see Maestripieri, 2002,
experience of labor and delivery (Chen et al., 1999; for review of literature). Because milk composition
Neville and Morton, 2001). For example, stressful represents a large investment by the mother, an exten-
births that result in cesarian section deliveries are com- sion of Trivers’s theory would predict that milk com-
monly associated with delayed expression of colostrum position would reflect the physiological conflict, or
(Dewey, 2001; Lau, 2001). Early initiation of breast- compromise, between what the infant wants and what
feeding, defined as suckling immediately following the mother is able to give. Infants may grow faster if
delivery, is aided by maternal breast odor (Porter and mothers produce milk with higher fat concentrations,
Winberg, 1999; Winberg, 2005) and offers considerable but mothers may be limited by their physiological
benefit to the newborn including aiding the postnatal energy stores. The amount of fat in the milk of extant
gastrointestinal-tract transition. The skin-to-skin con- mammals, including humans, is thus a compromise
tact associated with suckling appears to help regulate between infant energy needs for growth and develop-
temperature and blood glucose levels (Winberg, 2005 ment and maternal abilities to access fat in the diet, or
citing Christenssen et al., 1992). In turn, the close con- store fat on her body and mobilize those fat stores
tact and suckling creates physiological responses in the during lactation (Oftedal, 2000).
mother. Suckling appears to improve the efficiency Among primates, the duration of lactation is rela-
of maternal energy conversion through improved use tive to body size and among many species, including
of ingested calories as a result of increases in gas- apes, exceeds gestation in energy requirements and
trointestinal-tract hormone release (Winberg, 2005). length (Harvey et al., 1987; Ross 1998, 2003). Indeed,
Suckling also releases higher levels of oxytocin, a hor- the life history of primates is considered one of
mone thought to have an impact on the maternal the “slowest” among mammals (Harvey et al., 1987;
brain, especially spatial learning and memory (Kinsley Charnov and Berrigan, 1993). Primate milk composi-
et al., 1999; Monks et al., 2003). These very early inter- tion is argued to reflect this derived life history pattern
actions between newborn and mother help regulate a (Oftedal, 1984; Oftedal and Iverson, 1995; Sellen,
more mutual physiological interaction but also appear 2007). Relative to other mammalian orders, primates
to play a critical role in the process of mother/infant produce milks that are low in fat, protein, and dry
attachment (Porter and Winberg, 1999; Insel and matter, and high in lactose. Within the primate order,
Young, 2001) and thus reproductive success. however, significant interspecific (Oftedal, 1984;
Oftedal and Iverson, 1995; Milligan, 2007; Milligan
et al., 2008a; Milligan and Bazinet, 2008) and intraspe-
LACTATION cific (Lönnerdal et al., 1984; Tilden and Oftedal, 1997;
Power et al., 2002, 2008; Hinde, 2007a, 2007b; Milligan
Lactation represents an energetically expensive phase et al., 2008b) variation has been identified. Primates
of reproduction for all mammalian mothers (Gittleman diverge from other mammalian orders in the lack
and Thompson, 1988; Oftedal and Iverson, 1995). It of correlation between body size and energy in milk
requires mothers to mobilize and transfer large quan- (Power et al., 2002). Variation may instead relate to the
tities of nutrients in milk, placing nutrient demands on rate of somatic growth, with faster-growing primate
the mother (Oftedal, 2000). Mammalian mothers meet species producing milks with more energy from pro-
these demands by increasing the energy in their diet tein (Oftedal, 1984; Power et al., 2002; Milligan, 2007).
(Altmann, 1983; Forsum et al., 1992; Sauther, 1994; Energy from fat also is highly variable both within and
Butte et al., 1999; Oftedal, 2000), reducing energy output among nonhuman primate species (Milligan, 2007).
(Roberts et al., 1985; Panter-Brick, 1993; Piperata and One explanation for this variability may be infant
Dufour, 2007), or by storing nutrients during periods sex. Primiparous rhesus macaque mothers produce
significantly higher fat milks, and thus higher energy food items. This adaptation is tied to timing and flexi-
milks, for sons compared to daughters (Hinde, 2007b). bility of weaning. Taken together, these adaptations
Variation may also relate to maternal energy balance. allow human mothers to resolve trade-offs between
Old and New World monkey mothers in positive energy the high energetic cost of lactation and infant morbid-
balance may be able to convert excess energy intake ity and mortality. While complementary feeding may
into milk energy, producing milks with significantly be a critical aspect of the human lactation strategy,
more energy than predicted for a primate (Milligan, it may not be a unique attribute. Among nonhuman
2007). As is true in humans, milk fat is the most vari- primates, the transition from milk to nutritional
able component of nonhuman primate milk composit- independence is a process rather than a particular
ion and the most malleable with respect to ecological point in time, with infants nursing long after the inclu-
variation (Oftedal, 1984; Oftedal and Iverson, 1995; sion of other food items into the diet (Lee et al., 1991;
Power et al., 2002, 2008; Milligan et al., 2008a). These Lee, 1996, 1999).
results suggest significant flexibility among nonhuman The high concentration of immune factors in
primate mothers in milk composition. Intraspecific human milk is well documented but little comparative
variation in age at weaning (Harvey et al., 1987; work has been done to determine if this is species-
Ross, 1998, 2003) further supports the picture of a specific, or a primitive aspect of primate lactation
primate lactation strategy that is extremely flexible (but see Lönnerdal et al. 1984). Research on rhesus
and responsive to current ecological conditions and macaque milk (Milligan, 2005) suggests that human
future reproductive events. milk may be unique among nonhuman primates in its
Like nonhuman primate milks, human milk is high concentration of secretory immunoglobulin
dilute, low in fat and protein, and high in lactose A (sIgA). The cultural changes associated with agricul-
(Jenness, 1979; Lönnerdal and Atkinson, 1995; Oftedal ture, including increased population density and a
and Iverson, 1995; Prentice, 1996). Humans also exhibit more sedentary lifestyle, promoted an increase in
variability in milk composition (Prentice, 1995), flexibil- infectious diseases, thereby creating a novel ecological
ity in the duration of lactation (Dettwyler, 2004; setting for human populations (Cohen, 1989; Barrett
Kennedy, 2005) and flexibility in meeting the costs of et al., 1998). Increases in number of pathogens and
lactation (Forsum et al., 1992; Panter-Brick, 1993; Butte pathogen virulence would have placed strong selective
et al., 1999; Piperata and Dufour, 2007). As argued by pressure on the human immune system, particularly
Dufour and Sauther (2002), the human lactation strat- the immune system of infants and children and may
egy most likely differs from nonhuman primates in have selected for increased immune factors in milk to
degree, rather than kind. increase neonatal and infant survival (Milligan, 2005).
Several aspects of human milk composition and the
larger human lactation strategy have been argued to be
Milk is generally buffered from maternal
derived traits in humans. These include the concentration
condition, with some exceptions
and/or composition of long-chain polyunsaturated fatty
acids (LCPUFA) (Martin, 1983; Vasey and Walker, 2001), Supplementation experiments are used to determine
the use of complementary foods during weaning (Sellen, the effect of diet on milk composition (see Prentice,
2007), and immunological components (Slade and 1995, for review of literature). Providing malnourished
Schwartz, 1987; Goldman, 1993; Goldman et al., 1998). women (determined by a body mass index [BMI]
In a test of Martin’s hypothesis for unique LCPUFA < 18.5) in The Gambia with biscuits containing pro-
composition of human milk, Milligan et al. (2008a) tein, calcium, and/or carbohydrate resulted in little
and Milligan and Bazinet (2008) found that the range to no change in milk composition or milk volume
of LCPUFA composition of anthropoid milks, includ- (Prentice, 1995). Nutritionally compromised women
ing the highly encephalilzed Cebus monkey and several show similar concentrations of milk protein to well-
species of hominoid, was identical to cross-cultural nourished women (Prentice, 1995; Prentice and Pren-
findings on human milk LCPUFA. Like human milk, tice, 1995), suggesting that even low levels of dietary
nonhuman primate milks are highly variable in doco- protein intake allow for production of milk with the
sahexaenoic acid (DHA) composition with respect to necessary concentration of protein for optimal human
dietary intake of DHA. Higher levels of milk DHA and infant (somatic) growth. Indeed, Prentice and Prentice
other LCPUFA are predicted in any primate population (1995) found the macronutrient content of human
that consumes foods with preformed sources of DHA breast milk (protein, fat, lactose) to be surprisingly
(Milligan and Bazinet, 2008). insensitive to maternal dietary differences.
Sellen (2007) argues that a flexible complementary Changes were observed when supplementation
feeding strategy is a derived feature of human lacta- involved fatty acids and vitamin B12 (Prentice and
tion. Complementary feeding describes the transition Prentice, 1995); supplementation of the maternal diet
from exclusive breast-feeding to the inclusion of other with these factors increases their composition in milk.
Milk fatty acid profiles are most affected by maternal to 3 5% of the maternal brain volume during the last
diet, as dietary fat is one source for milk fat. The other trimester (Holdcroft et al., 1997), probably because of
two sources of milk fat are de novo synthesis within the the high concentration of essential fatty acids, particu-
mammary gland and depot fat transferred through larly DHA, in this tissue (Vasey and Walker, 2001).
the maternal bloodstream (Stini et al., 1980; Prentice, After birth, fat stored in the mother’s hips and thighs
1996). Human milk fatty acid profiles vary within and can be converted into milk; fuel for the metabolic
between populations because they are so intimately requirements of the growing infant brain.
tied to dietary habits and maternal condition (Koletzko Investigations on the relationship between mater-
et al., 1992, 2001; Sanders, 1999). This is especially true nal body composition and milk composition indicate
for LCPUFA, such as DHA, which are supplied directly that there is not a strong relationship between energy
from the maternal plasma (from the diet or depot fat balance and milk quality. Although human populations
stores) or as metabolites of precursor fatty acids in the vary with respect to maternal energy balance, human
maternal diet (e.g., a-linolenic acid, ALA). Variation in milk fat (and energy) is relatively conserved and
LCPUFA concentration is attributed directly to dietary appears to be as variable within females (and popula-
differences in foods containing these fatty acids. For tions) as between females (and populations) (Jensen
example, in a study of 9 human populations, Yuhas et al., 1995; Prentice, 1995). Women who have large
et al. (2006) found the percent composition of milk stores of depot fat (BMI > 26) were found to produce
DHA to range from 0.17% to 0.99% of total fatty acids. milk with higher fat concentration than women with
Those populations with the highest DHA values had low BMIs (<18). However, the higher BMI group pro-
higher fish consumption, the primary dietary source duced less milk than the lower BMI group (Barbosa
for DHA. Vegetarian mothers produced milk that con- et al., 1997). As a result of this inverse relationship
tained little to no fatty acids derived from animal fat between milk fat concentration and milk volume, the
and more fatty acids derived from dietary vegetable fat total amount of fat secreted into milk had no signifi-
(Finley and Lönnerdal 1985; Dettwyler and Fishman, cant association with maternal body fat (Butte et al.,
1992). Agostoni (2005) offers an interesting perspective 1984; Barbosa et al., 1997). Even when milk volume is
on LCPUFA fatty acids in milk. He proposes that ignored, the difference in milk fat production between
fetuses may become accustomed to the supply of fatty these two groups was small (2.73 0.37% vs. 2.89
acids from their mother during intrauterine life. 0.35%) and well within the range of variation reported
Infants are “imprinted” with a specific fatty acid pat- for populations of well-nourished women (Jensen
tern during gestation, and their fatty acid metabolism et al., 1995). Probably as a consequence, these authors
may be “programmed” to the maternal environment (Barbosa et al., 1997) reported that infant growth
and the infant’s genetic background. velocities were not significantly different between the
Alternative sources of fat in milk production allows low and high BMI groups.
for contingencies or compensatory actions when envir- Because milk fat is the main energy source for
onmental conditions do not permit adequate dietary human infants, supplying more than 50% of the calories
intake of fat. Most important for humans may be (Jenness, 1979; Jensen et al., 1995), consistent produc-
the use of depot fat stores during lactation. Human tion of essential milk fat from diverse sources may have
females gain weight during pregnancy by way of fat been critical to fitness of the infant and the mother.
deposition (McFarland, 1997). Fat that is stored in the The reliance of reproductive females on stored fat also
hip and the thigh is more metabolically active during is established. If dietary intake of fat during lactation is
lactation than fat in other depots in the body and is low, human females compensate by utilizing fat from
also highly resistant to weight loss (McFarland, 1997). their depot stores (Emmett and Rogers, 1997). Indeed, it
When dietary fat is low, lactating women are able to is believed that women in undernourished populations
use fat from their depot fat stores as a source for milk are able to continue to lactate through reliance on fat
fat. Indeed, lactating women on low fat diets produced reserves (Jelliffe and Jelliffe, 1978).
more milk fat from subcutaneous depot fat rather It has been suggested that despite evidence that
than from dietary fat (Emmett and Rogers, 1997) or diet and nutritional status have only a small effect on
as a result of decreased physical activity (Schutz et al., milk composition and yield, there may be a threshold
1980). Fat content in milk is of particular importance below which the quality and quantity of milk may be
because the human brain is approximately one-third compromised (Lönnerdal, 1986; Emmett and Rogers,
lipid, all of which must be supplied to fetuses and 1997). Lönnerdal (1986) argues that there must be a
young infants by the mother in utero and in milk, lower limit of dietary nutrient intake below which it
respectively. The importance of maternal transfer of would be inadequate for milk production. However, of
stored fat to the infant during lactation therefore is the human populations investigated thus far (Prentice,
an extension of the pattern observed during gestation. 1995), breast milk composition and volume seem
Placental transfer of fat includes the mobilization of up to be very “well-buffered” (Jensen et al., 1995) against
ecological variability (Prentice et al., 1994). For example, becomes a necessary starting point for asking
Butte et al. (1984) found no relationship between milk questions about fitness and reproductive success.
quantity or milk quality and maternal anthropometric Pregnancy offers an essential window of opportunity
indices such as maternal weight, height, and body fat. to examine how a woman’s previous biological experi-
The lack of cross-cultural variation in human milk ences impact pregnancy outcomes and simultaneously
composition and the relatively small role played by allow us to examine the earliest of environments and
the environment in altering this composition seem to longer-term impacts of variable intrauterine experi-
support the view that milk composition in humans is ences. Lactation, argued here as a more fluid continu-
highly conserved. ation of the same reproductive strategy, also demands
a life span perspective. The evidence for metabolic
programming in utero and the links to the early
MILK AS CUES TO DISEASE ECOLOGY postnatal environment also argue for a broader more
inclusive framework. For example, early postnatal
Milk provides more than nutrition to the developing growth trajectories are strongly patterned by gesta-
infant. Nonnutritive immune factors that are passed tional duration and intrauterine growth and lactation,
from mother to infant (passive immunity) are neces- via suckling bouts and the composition of milk, helps
sary both for immediate immunocompetence of the facilitate this growth (Jochum et al., 2005; Kovacs
infant, and for enhancement and development of the et al., 2005; De Blasio et al., 2007). Agostoni’s, (2005)
infant’s immune system (Goldman et al., 1982, 1998; work on programmed fatty acid metabolism offers
Van de Perre, 2003). Additionally, breast milk contains similar support. Such data suggest we should follow
immune factors that stimulate the development of previous pleas (e.g. Dufour and Sauther, 2002;
the neonate’s intestine and play a critical role in the Ulijaszek, 2002; Sellen, 2007) and encourage future
neonate’s development of intestinal host immune studies that link nonhuman primate and human
defenses (Bines and Walker, 1991; Cruz et al., 1991). physiological flexibility and reproductive strategies for
The immune factors present in milk are well adapted a better understanding of how reproduction has been
to the environment in which they are needed: SIgA, conserved and modified across evolutionary time.
lactoferrin, and lysozyme are resistant to digestive Behavioral flexibility is a critical and potentially
enzymes and can persist in the gut without degradation integral part of the human life history strategy. Given
(Cruz et al., 1991; Goldman and Goldblum, 1995; the importance of behavioral flexibility in meeting
Lönnerdal, 1996). Most microorganisms enter the the demands of reproduction across human and non-
neonate through the mucosal tissues, and antibodies human primate species and our long-standing aware-
present in milk are thus able to react with and provide ness of the importance of contexts/environments
immunity against pathogens of mucosal surfaces, espe- shaping biology, a biosocial perspective offers another
cially enteric bacteria (Hoshower, 1992; Goldman et al., useful framework. The example of how fetal stress
1998; Goldman, 2001; Van de Perre, 2003). Indeed, the reactivity develops in response to maternal stress and
majority of sIgA antibodies are directed against enteric anxiety highlights the importance of social contexts.
pathogens (Cruz et al., 1991). What is especially import- Examining how social structures encourage or dis-
ant about these transformed maternal antibodies is that courage mother/infant attachment and broader social
they are specific to antigens that would be recognized support has long-term implications for infant/child
by antibodies in the gastrointestinal tract of the mother development and overall health. Flexibility in patterns
(Goldman, 2001). In this respect, sIgA antibodies of supplemental feeding, social support during repro-
ingested and utilized by the infant through the breast ductive events, and balancing maternal work demands
milk will be directed against pathogens encountered with infant feeding all require a nuanced understand-
by the mother (they are her memory B cells) and there- ing of how social contexts shape biological variation.
fore, pathogens the infant is likely to encounter in the Human evolutionary biology and social epidemi-
environment. Passive immunity conferred through ology are increasingly compatible and offer new
breast milk is an example of “inheritance” of an opportunities to examine how environmental contexts,
acquired characteristic, maintained by a genetic com- including social environments, shape local biologies
ponent subject to natural selection; the mother passes (Lock and Kaufert, 2001; Pike, 2005; Worthman and
her antigen experience to her offspring via milk. Khort, 2005). Trends suggest a stronger presence of
evolutionary interpretations for biomedical research
(e.g. Wells 2003; Bateson et al., 2004; Gluckman et al.,
CONCLUSIONS AND POLICY IMPLICATIONS 2007; Gluckman and Hanson, 2007; Smith, 2007,
among many others). Pregnancy and lactation offer
As our understanding of the importance of environments important opportunities to simultaneously examine
for gene expression expands, a life span perspective mechanisms that enhance reproductive success and
fitness and offer insights on pressing public health Armstrong, E. (1983). Relative brain size and metabolism in
concerns. A host of examples can be cited including mammals. Science, 220, 1302–1304.
preterm delivery (Pike 2005; Gluckman and Hanson, Barbosa, L., Butte, N. F., Villalpando, S., et al. (1997). Mater-
2007), sudden infant death syndrome (McKenna et al., nal energy balance and lactation performance of Mesoa-
1997; Mosko et al., 1997), complications associated merindians as a function of body mass index. American
Journal of Clinical Nutrition, 66, 575–583.
with birth (Rosenberg and Trevathan, 2002), comple-
Barker, D., Gluckman, P., Godfrey, K., et al. (1993). Fetal
mentary feeding strategies and infant survival (Sellen,
nutrition and cardiovascular disease in adult life. Lancet,
2007), and the implications of the evolution of fatty
341, 938–1001.
acid content of milk and infant formula (Uauy et al., Barrett, R., Kuzawa, C. W., McDade, T., et al. (1998). Emerging
1996; Carlson, 1999, 2001; Gibson and Makrides, 1999; and re-emerging infectious diseases: the third epidemi-
Agostoni et al., 2001) among so many others. We hope ological transition. Annual Review of Anthropology, 27,
this chapter, and the volume more generally, further 247–271.
encourages the exploration of evolutionary under- Bateson, P., Barker, D., Clutton-Brock, T., et al. (2004).
pinnings of pressing public health concerns. Developmental plasticity and human health. Nature, 430,
419–421.
Bines, J. E. and Walker, W. A. (1991). Growth factors and the
DISCUSSION POINTS development of the neonatal host defense. Advances in
Experimental Medicine and Biology, 310, 31–39.
1. How does life history theory enhance our ability to Bowman, M. E., Lopata, A., Jaffe, R. B., et al. (2001).
Corticotropin-releasing hormone-binding protein in pri-
understand the evolution of primate reproduction?
mates. American Journal of Primatology, 53, 123–130.
2. The authors’ propose the idea that the primate
Brouwers, E. P. M., van Baar, A. L. and Pop, V. J. M. (2001).
reproductive strategy is best examined as an inte-
Maternal anxiety during pregnancy and subsequent infant
grative strategy that crosses pregnancy, birth, and development. Infant Behavior and Development, 24, 95–106.
lactation. What are the strengths and weaknesses Butte, N. F., Garza, C., Stuff, J. E., et al. (1984). Effect of
of such an integrative approach? maternal diet and body composition on lactational perform-
3. How does our understanding of pregnancy and ance. American Journal of Clinical Nutrition, 39, 296–306.
lactation benefit from a comparative perspective Butte, N. F., Hopkinson, J. M., Mehta, N., et al. (1999).
across primate groups? Provide examples of both Adjustments in energy expenditure and substrate utiliza-
conserved traits across primate groups and a trait tion during late pregnancy and lactation. American Jour-
specific to human reproduction. nal of Clinical Nutrition, 69, 299–307.
4. Provide evidence for the importance of reproduct- Carlson, S. E. (1999). Long-chain polyunsaturated fatty
ive energetics for primate females. acids and development of human infants. Acta Paediatrica,
5. How might a better understanding of milk composi- 88, 72–77.
Carlson, S. E. (2001). Docosahexaenoic acid and arachidonic
tion inform health policy?
acid in infant development. Seminars in Neonatology, 6,
437–449.
Chang, C. L. and Hsua, S. Y. T. (2004). Ancient evolution
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21 Male Reproduction: Physiology,
Behavior, and Ecology
Michael P. Muehlenbein and Richard G. Bribiescas
INTRODUCTION of contrasting offspring investment requirements that

stem from internal gestation. Mammalian females pro-
Women and men exhibit vast differences in reproduct- duce relatively small quantities of large, energy-rich
ive physiologies, behaviors, and ecologies. The present gametes, and must energetically commit to gestation
chapter aims to illustrate these fundamental differences and lactation in addition to other postnatal activities
by utilizing recent theoretical and empirical develop- that increase the likelihood of offspring survival. Life-
ments in addition to clinical and anthropological data time reproductive success for females is therefore
that help clarify the evolutionary bases for human male largely limited by access to resources (Trivers, 1972).
reproductive functions. We begin with a discussion of Females set the pace of childbearing, and population
the various aspects of male reproductive effort, includ- fertility is determined by the length of interval between
ing the physiology and behaviors associated with seek- successive gestations. This interbirth interval is deter-
ing, attracting, and choosing mates, competing for and mined largely through robusticity of ovarian function,
controlling mates, paternal behaviors, and the proxim- length of lactational amenorrhea, likelihood of fetal
ate determinants of spermatogenesis, libido, and erec- loss, and coital frequency (Wood, 1994b). The male
tion. For the specific purpose of better understanding contribution to this is relatively low.
male reproductive ecology, we next provide readers Sexual reproduction and the exchange of genes
with a description of male reproductive physiology, followed by mutation, recombination, and independ-
including major aspects of development, endocrin- ent assortment function largely to create variation in a
ology, and senescence. Testosterone may be synonym- population (Fisher, 1932), which, among other things,
ous with maleness; however, it may impose a number of provides some advantage against pathogens also evolv-
costs, including negative energy balance, immunosup- ing in the environment (Van Valen, 1973). Humans are
pression, and prostate cancer. not parthenogenic, and males may make some contri-
A discussion on male reproductive ecology ends our butions to population fertility and the interbirth inter-
chapter because it draws from our discussions on repro- val, albeit much less so than that of females.
ductive effort and physiology. Readers are encouraged Unlike women, men are not constrained by the
to utilize the information presented here to further dis- direct metabolic costs of gestation, lactation, child-
cussion and research on human male reproduction, birth, or menstruation. Men, like other male mammals,
both the proximate mechanisms involved in addition are characterized by the continuous production of
to the evolutionary explanations for the ways we func- spermatozoa with the potential for inseminating many
tion and behave. females. Greater mate access can therefore increase
offspring production. Some males will be more suc-
cessful than others in the reproductive race, resulting
MALE REPRODUCTIVE EFFORT in high levels of reproductive variance. For example,
some men may not have any children whereas the
Reproductive effort refers to investments of both time Sultan of Morocco likely produced more than 800
and energy into reproduction. Optimization of repro- (Low, 2000). For all men, enhancement of evolutionary
ductive effort is of central importance, especially for fitness is possible through increased coital opportun-
capital breeding, iteroparous organisms that must ities. Beyond sexual performance, male reproductive
budget time and energy over a number of reproductive effort can include seeking, choosing, and attracting
events within a lifetime. Males and females differ mates, competing for and controlling mates, as well
greatly in the amount of time and energy they invest as protection and provisioning of offspring and mates.
in reproduction. For mammals, this is the direct result Below we discuss each of these concepts in detail.
351
352 Michael P. Muehlenbein and Richard G. Bribiescas
Given the scope of this text, homosexual preference age (Hill and Hurtado, 1996; Kuhnert and Nieschlag,
will not be considered here, but evolutionary and devel- 2004). Since there is no evidence of an analogous
opmental causes of homosexuality have been con- decline in male fertility, it may be that males simply do
sidered elsewhere (Roughgarden, 2009). not have access to fertile females due to female choice.
Compromised female partner fertility (menopause) is
also a factor in declining male reproductive value.
Seeking and attracting mates
Declination in attractiveness in addition to decreased
Males of some species will put so much effort into seek- ability to compete with conspecifics and acquire
ing a mate that they forgo eating during the breeding resources may reflect a type of “social andropause”
season, which can have serious effects on survivorship in elderly men (Bribiescas, 2006). Such shifts in re-
(McMillin et al., 1980; Bobek et al., 1990). Mate-seeking productive possibilities perhaps encourage men to dedi-
behaviors can compromise survivorship by increasing cate more time and energy into offspring and mate
day-range lengths and energy expenditure as well investment.
as exposure to predators. Sexual promiscuity also
increases the risk of sexually transmitted infections.
Choosing a mate
Despite this, a significant number of men surveyed
are willing to consent to sexual intercourse with a Because of the high costs of reproduction, females
potential partner they have only recently met (Buss should be under selection to choose carefully when
and Schmidt, 1993). and with whom they mate (Williams, 1966; Trivers,
Animal courtship displays can be quite complex, 1972). Female mate choice may be expressed to maxi-
with ornate and brightly colored or decorated males mize resources, protection, and paternal care in add-
vying for the attention of onlookers. The same can be ition to beneficial genetic variation that could be
said for humans, in which men may attempt to adver- passed to offspring. For example, females may favor
tise their resource potential by displaying resources mates that display honest indications of disease resist-
such as expensive cars and jewelry. Men, particularly ance (Hamilton and Zuk, 1982) or other attributes of
adolescent males, may participate in dangerous survivability (Zahavi, 1975). Human women of many
sporting behaviors to gain attraction. This does not sociocultural groups consistently exhibit preference
imply that such behaviors are consciously performed for older, intelligent, emotionally sensitive men who
for the purpose of mate attraction. Rather, psycho- are successful at their careers and are willing to invest
logical mechanisms have certainly been naturally financial and other resources, including parental care,
selected to maximize lifetime reproductive success. in a long-term relationship (Buss and Schmidt, 1993).
These may encompass dangerous behaviors that In fact, income and education (i.e., resources in gen-
attract attention and demonstrate survivability. eral) are the best predictors of lifetime reproductive
A man may also use his physique and/or intellect success in men (Mace, 1996; Waynforth, 1998). While
(i.e., education level) to attract a mate. The former women tend to prefer fewer short-term mates to long-
is augmented through the anabolic actions of term ones, they can also gain financial and “genetic”
testosterone and other androgens, and thus elevated resources by employing a short-term reproductive
testosterone levels and muscle anabolism may be con- strategy (see Chapter 17 of this volume for a complete
sidered direct investments in male reproductive effort discussion about human mating strategies).
(see below). At the same time, high doses of testoster- If afforded access to fecund females, male animals
one can compromise survivorship (also see below). may actually employ some mate choice. This is in con-
Despite this, rates of anabolic-androgenic steroid and trast to the long-standing “Bateman’s principle” in
other ergogenic drug use for both athletic enhance- which a male, because of the minimal costs of sperm
ment and improvement of appearance are increasing production, should be physiologically and behaviorally
in the United States. Adolescents are exposing them- “ready and willing” to mate at all times and be indis-
selves to these substances at an earlier age, with an criminate about his choice of mates. We now recognize
estimated 10% of high school male athletes taking male mate choice as a real phenomenon in various
illegal steroids (Calfee and Fadale, 2006). Anabolic- species. For example, male chimpanzees prefer to con-
androgenic steroid use can cause physical and psycho- sort and mate with older, parous females with proven
logical damages, including liver failure, depression, maternal skills (Muller et al., 2006). Estrus females of
psychosis, and rage (Hall and Hall, 2005). Future mor- various species are also more attractive to males
tality data from men taking androgen supplements will (Beach, 1976).
likely provide much-needed data on this interesting Mammalian males may exhibit mate choice precisely
experimental endocrine intervention. because the number of quality ejaculates is limited
Female reproductive value peaks during the 20s (Dewsbury, 1982). That is, the delivery system (ejacula-
regardless of population and declines gradually with tion) can outpace production (spermatogenesis), and it
Male Reproduction: Physiology, Behavior, and Ecology 353
may therefore pay for a male to choose who receives the choice and detection of fecundity has not yet been
ejaculate. Sperm counts do decline in some animals extensively studied.
following repeated ejaculations, which is especially the
case in insects (Odendaal et al., 1989). Furthermore, the
Competing for mates
refractory period between consecutive ejaculations
increases in a number of species, including primates Males may rely on various physical attributes in order to
(Small, 1988). The refractory period between consecu- increase reproductive fitness, including body size,
tive ejaculations can range from minutes to hours weaponry (e.g., canines), and sperm volume. The exist-
depending on physical condition (Aversa et al., 2000). ence of sperm competition implies that by increasing
An exception of this is known as the “Coolidge effect” in the volume of spermatozoa and ejaculate, males can
which the refractory periods between ejaculations outcompete each other for successful fertilizations
diminish with the presentation of novel receptive (Harcourt et al., 1981). Therefore, species with multi-
females (Beamer et al., 1969). In this regard, males can male groups have larger testes relative to body size than
partition ejaculates between females. Such phenomena those with single-male polygynous mating systems
have not been definitively demonstrated in humans. (Harvey and Harcourt, 1984).
Human male sperm counts do decline after each con- The existence of sperm competition in humans has
secutive ejaculation, but not to a point significantly low been debated, and it appears that sperm volumes in
enough to be considered infertile (Nnatu et al., 1991; coital ejaculates can vary as a function of duration of
Cooper et al., 1993). separation from their committed partners (Baker and
As with females, human males exhibit preference Bellis, 1989). That said, the role of sperm competition
for both long-term and short-term mating partners. In in our own species is reduced compared to chimpan-
men, these choices are based largely on fecundity, the zees; short-term bonding and intensive mating promis-
likelihood of fidelity, and maternal ability (Buss and cuity have selected for greater investment in sperm
Schmidt, 1993; Gangestad et al., 2005; Sugiyama, quantity and accessory gland development (i.e., sem-
2005). On average, men consistently exhibit preference inal vesicles) in chimpanzees (Dixson, 1999). Humans
for younger mates and more of them, reflecting pos- exhibit only mild sexual dimorphism (Smith and
sible selection for promiscuity towards highly fecund Leigh, 1998), but this may still be indicative of the large
women (Buss and Schmidt, 1993). Visual signs of fecu- role polygyny has played in our evolutionary past. In
ndity in women include a high breast-to-underbreast fact, approximately 80% of all human populations may
ratio (large breasts) and a low waist-to-hip ratio currently practice polygyny (Buss and Schmidt, 1993).
(narrow waist) (Reynolds, 1991; Tovee et al., 1999). Intrasexual competition is an important mechan-
Women with these characteristics tend to have higher ism of sexual selection (Trivers, 1972), and male–male
reproductive potential as measured through estradiol competition over access to fecund females is a common
and progesterone levels (Jasienska et al., 2004). phenomenon, even in humans. One way to compete for
Unlike females of some other species (Domb and access to mates is to dominate or enhance one’s status
Pagel, 2001), women do not exhibit sexual swellings over conspecifics, and testosterone is related to domin-
that advertise fecundity or reveal the time of ovulation ance-seeking behaviors in males in interesting ways. For
to males. However, scent may play some role in human example, testosterone increases in preparation for com-
mate choice. Pheromones are chemical signals petitions (Booth et al., 1989; Mazur, 1992). This may
released from apocrine glands of the skin to induce function to augment muscle tissue (especially upper
various physiological and behavioral responses body strength), which itself may have been selected to
(Albone and Shirley, 1984). For example, in rodents facilitate the production and use of weapons to settle
the presence of an adult male’s odor can cause females these male–male conflicts (Bercovitch, 2001). Elevated
to enter into estrus (the “Whitten effect;” Whitten, testosterone levels prior to competition may also
1956), miscarriages in pregnant females (the “Bruce improve co-ordination and cognitive performance,
effect;” Bruce, 1959), and cause females to enter increase self-confidence and motivation, as well as pos-
puberty earlier (the “Vandenbergh effect;” Vanden- sibly interfere with self-control. Results of competition
bergh, 1967, 1973). The importance of these chemicals also alter hormone levels: testosterone levels remain
in facilitating human reproduction is debated, but they high in winners and decline in losers, possibly to facili-
are likely to be more than just vestigial (Rodriguez tate further successful competition in winners, and
et al., 2000; Kohl et al., 2001). In women, female pref- temper provocative actions in losers (Booth et al.,
erence for male scents changes across the ovulatory 1989). Testosterone levels in men respond to, and are
cycle (Wedekind et al., 1995; Gangestad and Thornhill, determined by, dominance activity and status change
1998). Additionally, the pheromone androstenol may (Mazur and Booth, 1998).
enhance attractiveness of males to females (Filsinger Aggressive behavior with the intention of inflicting
et al., 1985). The role of pheromones in male mate physical or mental damage is one means of attaining
and maintaining dominance status. Although testoster- Controlling mates

one levels have been reported to correlate with aggres-
Another general strategy commonly employed by
sive behaviors in many species (Dabbs and Dabbs,
males of a number of species to gain access to females
2000), associations between testosterone and aggres-
is sexual coercion. One frequently noted variation of
sion in humans have proved relatively inconsistent.
this strategy is infanticide, the killing of an infant sired
Testosterone levels have been significantly correlated
by another male in order to gain reproductive access to
with self-reports of diverse antisocial behaviors,
the mother (Hausfater and Hrdy, 1984; Smuts and
including marital disruption and violence, in military
Smuts, 1993). The existence of such adaptive behaviors
personnel (Booth and Dabbs, 1993). Testosterone
in humans is debatable. Certainly the likelihood of
levels have also correlated with violence of crimes and
being fatally abused is much higher for stepchildren
peer ratings of toughness in prison inmates (Dabbs
compared to children living with both biological
et al., 1987, 1995). However, short-term administration
parents (Daly and Wilson, 1988).
of supraphysiological doses of testosterone in other-
Various aspects of modern humans demonstrate
wise healthy men (eugonadal, noncriminal) is unre-
relative degrees of male control/coercion over female
lated to various measures of anger and aggressive
reproduction. A number of modern human cultures
behavior (Tricker et al.,1996; Pope et al., 2000). There-
attempt to exert male-biased control over female repro-
fore, changing levels of testosterone may potentiate
duction. Religious and other institutional, judicial, and
pre-existing patterns of aggression, but fluctuations in
social systems have attempted to control human sexual
testosterone levels in normal individuals do not predict
morality and behaviors, particularly that of women
changes in aggressive behavior. Violent aggression and
(Kinsey et al., 1948, 1953). Arranged marriages, stric-
antisocial behaviors are more consistently associated
tures on divorce, anti-abortion campaigns, regulation
with serotonergic dysfunction, such as defect in the
or illegalization of prostitution, physical sequestration,
neurotransmitter-metabolizing enzyme monoamine
female genital mutilation, and dress codes (i.e., veils,
oxidase A gene, rather than high testosterone levels
chuddars, chastity belts, foot binding, etc.) are all
(Morell, 1993; Krakowski, 2003).
modern examples of institutionalized control of female
Fluctuations in testosterone levels are consistently
sexual expression (Potts and Short, 1999; Gruenbaum,
related to the frequency and intensity of reproductive
2001; Hendrix, 2004). Human male control over female
aggression in most species examined to date. That is,
reproduction has also materialized through sexual jeal-
testosterone is most consistently associated with
ousy and spousal abuse, sexual harassment, forced
aggressive behaviors during challenges with conspeci-
copulation, male adultery, asymmetry in parental
fics, mate guarding, the formation of dominance rela-
investment, and emphasis on female virginity (Potts
tionships, or establishment of territorial boundaries
and Short, 1999; Thornhill and Palmer, 2000).
(the “challenge hypothesis”; Wingfield et al., 1990).
Interestingly, synchronized estrous in some groups
Testosterone variation may therefore involve behav-
of female primates may have been selected to prevent
ioral and physiological manipulation in accordance
males from monopolizing receptive and ovulatory
with the needs to compete with conspecifics for repro-
moments (Zinner et al., 1994), increase paternal invest-
ductive opportunities.
ment (Alexander and Noonan, 1979), and reduce
Testosterone can reduce the refractory period
the likelihood of infanticide by confusing paternity
between action potentials running down the stria ter-
(Hrdy, 1979; Altmann, 1990). The phenomenon of syn-
minalis between the hypothalamus and amygdala,
chronized ovulation in group-living females may or
potentiating an aggressive response following the
may not exist in humans (McClintock, 1971; Strass-
correct stimuli (Kendrick and Drewett, 1979). Testos-
mann, 1999). Women, like females of many different
terone also reduces the amount of hypothalamic
species, also exhibit concealed ovulation with no
stimulation needed to generate an aggressive response
monthly sexual swellings.
(Bermond et al., 1982). Testosterone increases glucose
uptake and metabolic rate of muscle cells (Bhasin
et al., 1996; Tsai and Sapolsky, 1996), and stimulates
Sperm
fat catabolism and muscle anabolism (Welle et al.,
1992). In total, testosterone can prepare the body, Although healthy human males are capable of continu-
physically and mentally, for competition. The chal- ous production of gametes throughout a lifetime, there
lenge hypothesis and its context of reproductive are notable variations in sperm quality and quantity
aggression may be less applicable to humans because between individuals. Healthy sperm counts can vary
acute variation in androgens does not necessarily trig- between 1 and 120 million per milliliter of semen, with
ger behavioral changes. However, changes in testoster- clinically defined minimal limits between 10 and 60
one level before and during competition could still million per milliliter (Glass, 1991; World Health Organ-
function to prime a man’s mind and body. ization, 1999; Guzick et al., 2001). There may even be a
significant amount of variation in sperm counts American and European populations over the past cen-
between populations, with non-Western populations tury (Becker and Berhane, 1997; Swan et al., 2000) in
manifesting lower sperm counts compared to Ameri- addition to increased rates of testicular cancer and
can males (Fisch et al., 1996). The highest reported genital abnormalities (Giwercman et al., 1993). Other
sperm counts are among French men (102.9 million/ data suggest that testosterone levels have decreased
ml) while the Thai seem to be at the low end of the over the last two decades and that these changes are
spectrum (52.9 million/ml) (Fisch et al., 1996). How- independent of age, diagnosed illnesses, smoking, body
ever these numbers should be viewed with caution due fat percentage, or other lifestyle factors (Travison et al.,
to interlaboratory and counting method variability 2007). However, the results of such studies have been
(Matson, 1995). Large-scale longitudinal sperm and contested based on sampling biases (Saidi et al., 1999),
semen assessments from other countries indicate some changes in clinical norms (Bromwich et al., 1994), and
variation but none to suggest differences in fertility inappropriate statistical methods (Olsen et al., 1995;
(Tortolero et al., 1999; Seo et al., 2000). In general, Emanuel et al., 1998). We may also now be more likely
there is little evidence that any significant differences to identify, record, and treat these conditions than we
in sperm quantity between individuals or populations have been in the past.
would correlate with differences in fecundity (Polansky One popular hypothesis is that environmental pol-
and Lamb, 1988; Fisch et al., 1996). Sperm morphology lutants with endocrine activity (“endocrine disrup-
may be a better predictor of male fertility (Guzick et al., tors”) could interfere with normal endocrine function,
2001), although ultimately the contribution of sperm resulting in developmental abnormalities, infertility,
quality and quantity to couple fertility is uncertain and pathology (Sharpe and Skakkebaek, 1993). These
at this time. chemicals include phytoestrogens (natural endocrine
In some species, particularly arthropods, spermato- disruptors with estrogenic activity), xenoestrogens
genesis is energetically expensive (van Voorhies, 1992; (synthetic endocrine disruptors), and industrial con-
Gems and Riddle, 1996). The act of mating alone can taminants such as dioxins, biphenyls, heavy metals,
compromise survivorship in male fruit flies (Partridge pesticides, and others. It is possible that exposure to
and Farquhar, 1981). In contrast, energetic investment these chemicals could cause adverse developmental
in mammalian spermatogenesis is negligible, account- and reproductive events, especially following high
ing for less than 1% of basal metabolic rate in human levels of occupational exposure. Furthermore, high
males (Elia, 1992). It is therefore not surprising that levels of exposure could cause germline mutations that
spermatogenesis can withstand extremely taxing ener- result in transgenerational effects, such as decreased
getic circumstances. Exercise may affect sperm quality sperm count in subsequent male generations (Anway
and quantity only under endurance-training circum- et al., 2005). However, there is still little direct evidence
stances (Arce et al., 1993), but still not to a point where that normal exposure to these chemicals cause male
compromised fecundity becomes evident (Roberts reproductive malfunction in the general population
et al., 1993). Other factors like diet composition (Wong (Safe, 2000; Joffe, 2003; Pflieger-Bruss et al., 2004).
et al., 2000, 2003), photoperiodicity (Levine et al., 1992),
and body temperature (Mieusset and Bujan, 1995) may
Libido
be influential. Furthermore, variation in testosterone
levels does not correlate well with variation in sperm- A fear of diminished libido is likely to be one of the
atogenesis (Weinbauer and Nieschlag, 1990). High fol- primary reasons why a hormonal male contraceptive
licle-stimulating hormone and inhibin B levels exhibit may never achieve widespread adoption (Martin et al.,
modest links with lower sperm counts (Meeker et al., 2000). But the relationship between hormones and
2007). Genetic variation in luteinizing hormone (LH) sexual motivation is equivocal anyway. Male repro-
and follicle-stimulating hormone (FSH) production is ductive endocrinology is sensitive to perceived coital
evident in some individuals, sometimes leading to opportunities. For example, male rhesus macaques
reproductive disorders and compromised fertility (Ber- demonstrate increased testosterone levels in both the
ger et al., 2005; Lofrano-Porto et al., 2007). Variation in breeding and nonbreeding seasons when provided
FSH levels within the common range of variation is not access to females (Bernstein et al., 1977; Glick, 1984).
associated with differences in spermatogenesis. Indeed, Increased androgen levels would be beneficial to sup-
spermatogenesis is tolerant of a broad range of FSH port increased frequency of sexual activity (Rose et al.,
exposure (Kumar et al., 1997; Tapanainen et al., 1997). 1972) and actively establish and defend mating part-
However, severe FSH deficiencies can result in oligos- ners (Bernstein et al., 1977; Glick, 1984).
permia (low sperm count) or azoospermia (total lack Testosterone levels in men also increase with
of sperm). anticipation of a sexual encounter. For example, a clas-
Interestingly, some data suggest a significant sic study describes how a lone male conducting
decline in sperm counts, independent of age, in North research on a remote island weighed his daily beard
clippings as a gross androgen bioassay and found et al., 2005). Even in remote populations, ED is common
that his bear growth rate increased immediately prior among older men (Gray and Campbell, 2005). Further-
to leaving the island for female companionship more, the incidence of ED appears to be increasing
(Anonymous, 1970). More recently, a sample of hetero- worldwide, with more than 300 million adult
sexual men exhibited increased testosterone levels men expected to be afflicted with it in the year 2025
during short conversations with women (Roney et al., (McKinlay, 2000). The number of cases reported may be
2003). There was also a positive relationship between increasing due to the recent acceptance of discussing
change in testosterone and males’ ratings of female and diagnosing such ailments in the elderly.
romantic potential. A considerable amount of research efforts have now
Testosterone levels also change in response to gone into the treatment of ED, from penile implants
copulation, with significantly increased androgen and prostheses to pharmacotherepy (Fabbri et al.,
levels following the coital event (Dabbs and Mohammed, 1997). One of the most significant advances has been
1992). Likewise, exposure to erotic sensory stimuli is the development of sildenafil citrate (Viagra®, Pfizer
correlated with increases in testosterone levels in het- Inc.), an oral phosphodiesterase inhibitor that inhibits
erosexual men (Carani et al., 1990). It is difficult, how- the breakdown of nitric oxide-induced cyclic guanosine
ever, to identify any consistent relationships between monophosphate (cGMP), mimicking the effects of
variation in a man’s testosterone levels and actual nitric oxide by stimulating the relaxation of muscles
sexual motivation. In hypogonadal men, testosterone around the corpora cavernosa (Bivalacqua et al., 2000;
injections at high doses are related to increased fre- Argiolas and Melis, 2003).
quencies of erotic thoughts, erections, and sexual activ-
ity (Davidson et al., 1978). In contrast, testosterone
Paternal behaviors
supplementation in healthy, eugonadal men is unre-
lated to intensity of sexual feelings or activity (Buena A direct consequence of internal fertilization is that
et al., 1993). Therefore, testosterone levels appear to be men cannot be absolutely certain about their paternity.
associated with libido only in men with low testoster- The rate of human extrapair copulations may be as
one to begin with, such as during clinical deficiencies high as 30% (Baker and Bellis, 1995), and the world-
or prolonged abstinence. wide misappropriated paternity rate is around 2%,
Variation in testosterone levels does not correlate although it can be as high as 30% in cases of low
well with sexual motivation in healthy men. Rather, paternity confidence (Anderson, 2006). It is therefore
sexual motivation depends largely on previous sexual not surprising that natural selection has favored the
experiences. Testosterone and other hormones may production of behavioral mechanisms that predispose
increase the likelihood that a sexual stimulus will elicit men (in general) to invest more heavily in mating effort
sexual behaviors, but only in the context of appropriate than parental effort. However, humans are among the
stimuli. Similarly, androgens can reduce the amount of 5% of mammalian species that do exhibit some type of
stimuli required for an erection. They are, however, not paternal care (Clutton-Brock, 1991). Basic paternal
required to produce or maintain an erection. care is characterized not only by defense, but also by
holding, carrying, provisioning, and social interaction.
The level of paternal investment is directly correl-
Erection
ated with both paternity confidence (Anderson, 2006)
When afforded the capability of generating and main- and assessment of a wife’s fidelity (Apicella and
taining an erection followed by successful ejaculation, Marlowe, 2004). Physical resemblance between father
an elderly man can fertilize an ovum. Pablo Picasso and child can increase paternal care and resource
became a father at age 68, as did Charlie Chaplin at investment (Christenfeld and Hill, 1995). Phenotype
age 73. The major rate-limiting steps at this age are matching, or the recognition of common phenotypic
attracting a fecund mate and generating/maintaining traits such as appearance or odor, certainly plays some
an erection. Causes of erectile dysfunction (ED) can be role in kin recognition in primates and other animals
psychological, neuroendocrinological, and pharmaco- (Alberts, 1999; Parr and de Waal, 1999). For example,
logical in origin. Degeneration of the vascular system adult male baboons can differentiate between their
due to stress, disease, or lifestyle (diet and smoking) own offspring and unrelated juveniles and support
can interfere with the normal process of erection their own offspring more frequently during agonistic
(Caretta et al., 2006). The prevalence of ED ranges disputes (Buchan et al., 2003). Physical resemblance
from 10–22% among various countries (Rosen et al., between a human father and child is actually not more
2004), and the risk and degree of ED increases with common than that between mother and child, and
age, around 8% per year in men aged 45–60 (Kratzik misidentification of fathers of young children from
et al., 2005). At age 70, more than 50% of men will photographs is quite random, averaging around 50%
exhibit some form (minimal to severe) of ED (Kratzik (Brédart and French, 1999).
Unlike women, men are not required by their biol- of sperm by Sertoli cells. In general terms, the HPT axis
ogy to provide any care for offspring beyond the con- acts as a negative feedback loop. As sex hormones such
tribution of sperm. Human male biology does however as testosterone rise, it increases the likelihood of
respond in interesting manners to both pair bonding decreasing the production of GnRH and LH. Estradiol
and fatherhood. Such behaviors are characterized by also appears to have a significant effect on the negative
elevated prolactin and suppressed testosterone levels in feedback process on the hypothalamus (Hayes et al.,
men (Storey et al., 2000; Gray et al., 2004). Combined, 2000; Rochira et al., 2006). As testosterone levels
these may function to decrease interest and effort in drop, the production of GnRH and LH increases.
acquiring new mates as well as facilitate interest in Gonadotropin-releasing hormone and all downstream
paternal behaviors (Schoech et al., 1998) (see Chapter hormones are produced in a pulsatile fashion due to
16 of this volume for a more complete discussion). the initial neuronal impulses that trigger and maintain
GnRH secretion. Similar negative feedback loops
govern spermatogenesis although in a more attenuated
MALE REPRODUCTIVE PHYSIOLOGY fashion. As FSH rises, production of inhibin A and
B rise, which also have negative feedback effects on
Taking a step back for a moment, we wish to provide GnRH. Activin, another peptide, promotes FSH pro-
readers with some basic background on male reproduct- duction (Kronenberg et al., 2007).
ive physiology, in part because this may clarify some of The effects of androgens on male somatic, repro-
the above-mentioned discussion, as well as prepare the ductive, and behavioral development begin in utero
reader for our discussion of male reproductive ecology to (Knickmeyer and Baron-Cohen, 2006). Müllerian-
follow. From a life history perspective, male reproductive inhibiting factor, testosterone, and dihydrotestosterone
physiology has evolved to optimize energetic allocation promote defeminization and masculinization of the
decisions and to maximize lifetime reproductive success. genitalia (Grumbach and Conte, 1998). Testosterone
Investment in reproductive function and somatic tissue levels rise during mid-gestation and then fall prior to
reflective of reproductive effort are primary targets of birth (Siiteri and Wilson, 1974). There is a second rise in
hormonal action and therefore subject to significant testosterone level that falls again prior to the first year of
selection. That is, males with reproductive systems age (Forest et al., 1974). The functions of these surges
that were most efficient at allocating energy likely had in androgen levels are not completely understood,
higher lifetime reproductive success. Such efficiency can although they may play important roles in sexual differ-
emerge from variation in hormone levels, receptor entiation of the central nervous system as well as
number, receptor sensitivity, and perhaps genetic differ- priming of androgen target tissues (De Moor et al.,
ences in the coding and transcription of receptor and 1973; Waldhauser et al., 1981; Wilson, 1982; Corbier
hormone proteins. It is important to remember that the et al., 1992; Davies and Norman, 2002). Several factors,
evolution of male reproductive physiology was shaped by including genetic polymorphisms of pathway synthesis
paternal uncertainty and sex differences in offspring and clearance enzymes, nutritional status, immuno-
investment resulting from internal gestation. logical stress, and social stress during development
may play important roles in “programming” baseline
testosterone secretion for later adulthood (Allen et al.,
Endocrinology and development
2001; Bribiescas, 2001; Zitzmann and Nieschlag, 2001;
Male endocrine function is based on the hypothalamic- Muehlenbein and Bribiescas, 2005; Jakobsson et al.,
pituitary-testicular (HPT) system. The preoptic area of 2006; Muehlenbein, 2008). For example, populations
the hypothalamus, a small collection of neurons at the experiencing chronic energetic stress have lower insulin
base of the brain, secretes gonadotropin-releasing levels that may inhibit gonadotropin secretion, adoles-
hormone (GnRH) into a conduit called the hypophys- cent hormone priming, and subsequently lower adult
eal portal leading to the pituitary gland. Gonadotropin- testosterone levels (Bruning et al., 2000).
releasing hormone stimulates the production of two Differential testosterone levels between individuals
gonadotropins, luteinizing hormone (LH) and follicle- and populations (discussed in detail below) may be
stimulating hormone (FSH). Both of these gonadotro- caused by these early priming effects on receptor
pins are transcribed from specific genes and are com- number and sensitivity as well as HPT function in
posed of a common alpha dimer and a specific beta general. It is clear that priming effects of exogenous
dimer (Kronenberg et al., 2007). Luteinzing hormone testosterone in boys with delayed puberty enhances the
and FSH are therefore similar in molecular structure effects of growth hormone (Muller et al., 2004), and
but impose unique physiological functions. Luteiniz- that individuals with idiopathic hypogonadotropic
ing hormone is primarily responsible for stimulating hypogonadism, a condition characterized by a con-
the production of testosterone by Leydig cells in the genital deficiency of GnRH, can respond to exogenous
testes and FSH aids in the maturation and production GnRH if they have prior exposure to testosterone,
suggesting a priming effect (Spratt and Crowley, 1988). developed secondary sexual characteristics. They do
Among chronically undernourished Indian men, admin- not normally maintain a territorial range, are usually
istration of human chorionic gonadotropin (hCG, a tolerated by flanged males in the area, and have been
potent stimulator of testosterone production) resulted observed force copulating with females (Mitani, 1985).
in a substantially muted testosterone increase compared Adults of each phenotype may be of reproductive age
to well-fed controls (Smith et al., 1975). Testosterone but exhibit different hormone profiles. The unflanged
variation between adult individuals and populations males appear to be developmentally stunted with lower
may be the result of similar effects prior to reproductive androgen, gonadotropin, growth hormone, and thyroid-
maturation. stimulating hormone levels compared to flanged males,
Puberty is a pivotal point in the life history of a yet both are reproductively capable (Maggioncalda
male, marked by a shift in reproductive and somatic et al., 1999, 2000). By maintaining a smaller body size,
investment from survivorship to reproductive effort. unflanged males are tolerated by flanged males and do
Androgens (particularly the reduction of testosterone not pay the costs of increased energetic expenditure
to dihydrotestosterone) control hair, vocal cord and and immunosuppression caused by higher androgen
genitalia development, fat catabolism, and skeletal levels, although they still gain access to some repro-
muscle anabolism in boys. Increases in adrenal andro- ductive opportunities. The development of this alterna-
gens anticipate the pubertal rise in sex steroids. The tive phenotype in other males may be triggered by
process, known as adrenarche, promotes the desensi- harassment from the fully flanged male, the release of
tization of the hypothalamus to androgen levels and pheromones from the flanged male, or even via their
contributes to the onset of puberty. Growth of the vocalizations. The hypothalamus does possess numer-
adrenal gland increases levels of adrenal androgens ous auditory connections, and thus an auditory signal
that in turn desensitize the hypothalamic negative could theoretically affect GnRH secretion from the
feedback response, resulting in greater tolerance for hypothalamus, altering the developmental process of
higher levels of androgens such as testosterone (Conley the animal (Ronnekliev and Resko, 1990). Either way,
et al., 2004; Campbell, 2006). See Chapter 8 of this these alternative male phenotypes are viewed as adap-
volume for a longer discussion of adrenarche. tations to the social environment.
Timing of the onset of pubertal maturation may be Social factors may also influence variation in
affected by environmental factors such as activity, life- human developmental timing. For example, Ellis and
style, and nutrition. Kulin et al., (1984) reported lower Garber (2000) have reported that girls who are raised
levels of urinary LH in malnourished Kenyan boys. in families characterized by relatively high levels of
Later puberty in boys in association with chronic ener- stress (e.g., history of maternal mood disorders, stress-
getic stress is also evident among the Turkana of Kenya ful interpersonal relationships, lack of resources, bio-
and the Tonga of Zambia (Campbell et al., 2004, logical father absence, stepfather presence, etc.) may
2005a). The effects on fertility are unknown although mature more quickly, although the relevant effect size
well-nourished boys tend to be larger, have greater appears to be very small. Presence of an alternative
body mass, and higher testosterone levels as adults. father figure may trigger earlier development in peri-
There is such an association between larger body size pubertal women in order to facilitate mating between
and higher fertility in Aché men and women of Para- the female and unrelated male. Alternatively, the pres-
guay (Hill and Hurtado, 1996). ence of a stepfather may contribute to family discord,
Social factors such as group composition may also resulting in psychopathology, and earlier maturation
influence variation in developmental timing. For in females may facilitate dispersal from the unstable/
example, in rodents, exposure of female pups to adult dangerous environment. Future studies should be
males is associated with accelerated maturation designed to investigate similar effects in males. It is
whereas exposure to adult females can cause delayed likely that the energetic determinants of menarche
sexual maturation (Vandenbergh, 1967, 1973). In and pubarche far outweigh any social determinants.
response to social cues, males from a variety of species Given the amount of phenotypic variation in
can exhibit alternative adult phenotypes with different humans, it is not possible to categorize men into alter-
reproductive strategies. Such alternative male pheno- native reproductive phenotypes. Different men cer-
types/strategies have been demonstrated in lizards, tainly practice different reproductive strategies. Men
reef fish, and primates. An excellent example includes also consistently develop later than women, and it has
orangutans for which there are two morphotypes been suggested that earlier maturation in females may
of adult males. “Flanged” males are those with fully allow women to acquire important parenting skills
developed secondary sexual characteristics (e.g., large while still being subfecund whereas delayed matur-
cheek pouches) that usually maintain a territorial ation in males may postpone direct competition with
range and mate with resident females (Mitani, 1985). other males for access to mates and allow for attain-
The “unflanged” males are much smaller, lacking fully ment of larger body size (Bogin, 1999). In this manner,
Epididymis
Seminiferous
tubule Spermatids
Spermatocyte
Basement
Acrosome inhibin, and testosterone are all involved in the matur-
membrane
Head ation process. Immature sperm are passed from
Midpiece Nucleus
Mature
sperm
the rete testes, to the vasa efferentia, and ultimately
Centrioles
stored in the epididymis where they are mixed with
Tail
seminal fluid (semen) produced by the seminal vesicle
and prostate gland. At this stage, the sperm become
Spermatogonia
Mitochondria Tail
fully motile. During ejaculation sperm and semen
Vas deferens
Testicle with coiled
seminiferous tubules
are ejected through the vas deferens and out through
the urethra.
21.1. Testicle and sperm morphology. Figure reprinted with
permission from Raven and Johnson (1988). In order to complete coital intromission, the penis
must increase its rigidity through the production
and maintenance of an erection. In a flacid state,
human pubertal timing for both males and females blood circulation through the penis is unrestricted.
may be an adaptation to maximize lifetime reproduct- Controlled by the parasympathetic aspect of the auto-
ive success in response to environmental cues. nomic nervous system, blood enters the base of the
penis, circulates down the shaft, to the head (glans
penis) and back out to the body. In a healthy man,
Spermatogenesis and erectile function
sexual stimuli induce changes in neurotransmitter
Spermatogenesis is the process of the production of levels, specifically elevations in nitric oxide levels in
male gametes. It is a 64 day cycle in which haploid nerve terminals of the penis which then activates for-
germ cells (spermatogonia) eventually develop into mation of the enzyme guanylate cyclase. This enzyme
mature sperm. Spermatogenesis takes place within causes increased formation of cGMP with consequent
the seminiferous tubules in the testes (Figure 21.1). decreases in intracellular calcium levels in corpora
Separating the seminiferous tubules is interstitial cavernosa (erectile body) muscle cells. Relaxation of
tissue which contains Leydig cells, the primary source this tissue allows for increased blood flow and subse-
of testosterone. The stages of sperm development are quent engorgement (Andersson and Wagner, 1995;
quite distinct. Germ cells, known as spermatogonia, Wagner and Mulhall, 2001).
initially divide mitotically to form spermatocytes.
Spermatocytes slowly migrate through interstitial
Senescence
space between Sertoli cells that aid in their maturation
and development. Leydig cells also provide endocrine Human senescence can be broken down into two basic
support for spermatocyte maturation. An initial pro- components, somatic and reproductive. In life history
cess of meiosis results in haploid secondary spermato- theory, senescence is unique from aging in that senes-
cytes. During a second meiotic division, spermatids are cence is the manner, timing, and rate at which physio-
formed. During the final stages of maturation, the logical aspects lose functional capacity and efficiency,
acrosome and tail develop before they pass into the ultimately leading to death (see Chapter 31 of this
lumen of the seminferous tubule. In total, about 300– volume), whereas aging can be viewed as the passage
600 sperm per gram of testicular tissue are produced of time. This is a key conceptual difference in life
(Nussey and Whitehead, 2001). Unlike oogenesis, some history theory since patterns of senescence reveal
daughter spermatogonia do not complete the matur- much about the energetic and time constraints that
ation cycle and revert to a primordial stage, therefore molded the evolution of a species. Endothermy,
allowing a virtually inexhaustible number of sperm to ectothermy, body size and metabolic rate, and extrinsic
be produced. However, most daughter cells undergo mortality (i.e., predation) all contribute to the evolu-
several divisions and ultimately produce spermatids tion of senescence. For example, a tortoise and a
and complete cell differentiation. mouse may be of equal age, say three years old, but
Sperm consist of three basic components, the head, exhibit very different patterns of senescence. Mice,
tail, and nucleus. The head consists of the nucleus as who are endothermic and small, have high metabolic
well as the acrosome, which contains enzymes that rates and spend a relatively great amount of energy
allow penetration of the ova and deposition of its gen- on early sexual maturation and reproduction due
etic material. The tail contains numerous mitochon- to high extrinsic mortality, hence their short life
dria and flagellates vigorously to propel the sperm spans. Interestingly, rates of senescence differ signifi-
towards the ova. Some sperm are however defective cantly between humans and chimpanzees living in
and do not swim correctly or have multiple heads or the wild and in captivity (Hill et al., 2001), suggesting
tails (Guzick et al., 2001). Because so many sperm that decreases in extrinsic mortality may have been
are produced, gamete quality control is less rigorous an important aspect of human evolution (Kaplan
than in oogenesis. Various hormones such as FSH, et al., 2000).
Reproductive senescence in human males is dis- Somatic changes with age are also common. Muscle
tinct from menopause in women. Unlike menopause, mass declines and adiposity increases (Guo et al., 1999).
there is no abrupt cessation of reproductive function Free testosterone is associated with muscle mass and
and onset of permanent infertility. In men, declines in negatively associated with fat mass in elderly men in
reproductive function are more subtle and exhibit a Western countries (van den Beld et al., 2000). Basal
wide range of population variation. Male reproductive metabolic rate decreases with age in tandem with lower
senescence may involve declines in fertility although testosterone (Fukagawa et al., 1990). Strength also
further evidence is needed (de La Rochebrochard et al., declines with age, a characteristic of male aging that is
2006). Various studies have reported deterioration of shared across populations (Walker and Hill, 2003).
sperm morphology and motility with age in otherwise Interestingly, peak hunting efficiency occurs decades
healthy men (Schwartz et al., 1983; Kidd et al., 2001), after the height of physical strength and performance
whereas other studies have not (Andolz et al., 1999; in Aché men, suggesting a decoupling between foraging
Tortolero et al., 1999). Genetic abnormalities are more efficiency and strength as well as an increased reliance
common in sperm of older men (Plas et al., 2000), and on skill, planning, and experience (Walker et al., 2002).
older men are at increased risk of producing children
with autism (Reichenberg et al., 2006) and schizophre-
Costs of testosterone
nia (Malaspina et al., 2001).
Sex hormone levels also tend to change with age, Although most readers might assume that testosterone
although such changes are not ubiquitous across popu- and other androgens are synonymous with maleness in
lations. In a meta-analysis of several populations in most cultures, the fact is that male physiology imposes
which all laboratory analyses were conducted using costs to survivorship beginning at a young age. Male
the same assay protocol, Ellison et al. (2002) showed fetuses and newborns exhibit higher mortality than
that while Boston men exhibited the standard decline in females (Kellokumpu-Lehtinen and Pelliniemi, 1984;
testosterone, other populations showed a more modest Byrne and Warburton, 1987; Ingemarsson, 2003). The
decline and others none at all. More refined differences average life span of a woman in almost all populations
among Japanese men included a testosterone decrease is significantly longer than a man’s (Buettner, 1995). In
from the second decade of life until their 40s. However, order to maintain some equilibrium between the
testosterone then remained unchanged well into their sexes in a population, the sex-ratio at birth needs to
70s (Uchida et al., 2006). Increases in sex hormone be slightly male-biased, which is typically the case
binding globulin (SHBG) contribute to declines in free (Parazzini et al., 1998). In young adulthood, the
testosterone (Gray et al., 1991; Harman et al., 2001). chances of a male being murdered rises dramatically
Changes in estradiol are sometimes also evident with compared to a female, and men account for over 85%
age, although this may be the result of increased adipos- of violent crime committed in the United States (Daly
ity and aromatization (Vermeulen et al., 2002), and and Wilson, 1983). In fact, it is safe to say that high
decreases have also been reported (Orwoll et al., 2006). mortality (relative to females) is a male characteristic.
In most well-nourished populations testosterone
exhibits a modest steady decline after the age of 40 Energetic costs
while LH and FSH exhibit a steady rise, most likely As discussed above, the energetic burden of spermato-
due to decreased testicular receptor sensitivity. There genesis varies by species. For some, like Drosophila and
is little or no variation between populations in gonado- Caenorhabditis, spermatogenesis can be expensive,
tropin changes with age. Among Aché men of Para- whereas for mammals it is not (Elia, 1992; Gems and
guay, testosterone levels were significantly lower Riddle, 1996). In men, sperm quality or quantity are
compared to US men and exhibited no decline with relatively unaffected by even long-term, high energetic
age. However, FSH and LH were positively associated output (Bagatell and Bremner, 1990). However,
with age, as is common in other populations suggest- attaining and maintaining adequate musculoskeletal
ing that this aspect of male reproductive senescence is function (e.g., skeletal muscle mass, red blood cells, cor-
not subject to environmental variability (Bribiescas, tical bone density, etc.) are energetically taxing. This
2005). Of further interest is the decline in hypothal- would reflect an investment in male reproductive effort
amic sensitivity to energetic status in older men. by augmenting inter- and intrasexual competition (i.e.,
Fasted older men fail to exhibit any improvement in male–male conflict and female sexual coercion), mate
LH pulse number or amplitude in response to GnRH attraction, and protection of mates and offspring. Given
administration compared to younger men (Bergendahl the energetic demands of musculoskeletal function, such
et al., 1998). Perhaps a previously unrecognized aspect an investment could compromise survivorship under
of male reproductive senescence is the compromised conditions of resource restriction (Bribiescas, 2001).
ability to adjust reproductive function in response to Muscle anabolism is enabled through the actions of
energetic availability (Bribiescas, 2006). testosterone and other androgens (Bhasin et al., 1996;
Tsai and Sapolsky, 1996). In addition to anabolic function as well as general health perceptions in a
effects, testosterone stimulates adipose tissue redistri- number of cohorts, including elderly, obese, and HIV-
bution (Marin et al., 1992a, 1992b; Welle et al., 1992). infected men (Marin et al., 1992a, 1992b; Wilson et al.,
Altered somatic composition and increased energetic 2000). However, the effects of testosterone supplemen-
costs due to elevated androgen levels can result in tation on immune parameters in these individuals are
a negative energy balance that can compromise not well investigated. It appears that varying doses of
survivability. This has been demonstrated in various testosterone do not significantly alter C-reactive pro-
species of birds and reptiles (Marler and Moore, 1988; tein levels in healthy eugonadal males (Singh et al.,
Ketterson et al., 1992; Marler et al., 1995). In men, 2002). Similarly, testosterone supplementation does
skeletal muscle tissue accounts for approximately not cause changes in absolute and percentage CD4þ
20% of basal metabolic rate (Elia, 1992), and this and CD8þ cell counts and plasma HIV RNA copy
measure surely increases during periods of high activ- number in HIV-infected men (Bhasin et al., 2000).
ity. Elevated testosterone levels and metabolic rates Given the popularity of testosterone supplementation,
could not only contribute to elevated production of both legal and illegal, research investigations should be
free oxygen radicals (Zirkin and Chen, 2000) but also specifically designed to more adequately determine
reduced tissue and organ maintenance in humans any negative effects on immune functions. In vitro
(Bribiescas, 2001; Muehlenbein and Bribiescas, 2005). analyses clearly indicate that testosterone can inhibit
lymphocyte proliferation and activity, and antibody and
Immunosuppression cytokine production (Weinstein and Bercovich, 1981;
Elevated testosterone levels could compromise survi- Daynes and Araneo, 1991; Grossman et al., 1991, 1995;
vorship by causing suppression of immune functions. Olsen and Kovacs, 1996; Giltay et al., 2000; Straub and
These immunoregulatory actions of testosterone are Cutolo, 2001; Burger and Dayer, 2002; Wunderlich
based on: (1) comparing male and female differences et al., 2002).
in immunocompetence; (2) examining associations In addition to causing immunosuppression, ele-
between circulating endogenous testosterone levels vated testosterone levels could also compromise survi-
and measurements of immune function, such as size vorship by decreasing the amount of energy and
of immune organs or lymphocyte counts in healthy or nutrients available for somatic repair and the mainten-
parasitized animals; (3) experimentally manipulating ance and activation of immune responses (Wedekind
testosterone levels through castration or supplementa- and Folstad, 1994; Sheldon and Verhulst, 1996;
tion and observing subsequent effects on immunocom- Muehlenbein and Bribiescas, 2005). Investment in
petence; and (4) performing in vitro analyses of immune- male reproductive effort generates a significant ener-
endocrine interactions (for a complete review, see getic demand that will theoretically trade-off with the
Muehlenbein and Bribiescas, 2005). competing energetic demands of immunocompetence,
In brief, males tend to be more susceptible to a which would increase susceptibility to disease or other-
variety of diseases, and both prevalence and intensity wise negatively affect convalescence (Sheldon and
of infection is often higher in males than in females Verhulst, 1996; Raberg et al., 1998, 2002; Verhulst
(Poulin, 1996; Zuk and McKean, 1996; Fedigan and et al., 1999; Owens, 2002; Schmid-Hempel, 2003;
Zohar, 1997; Moore and Wilson, 2002). For example, Muehlenbein and Bribiescas, 2005). Such effects may
the rate of primary and secondary syphilis is greater in be more exaggerated in energetically limited popula-
American men than women, and the incidence of syph- tions, and more muted in well-nourished populations.
ilis in men continues to increase (CDC, 2009). However, Immunocompetence is energetically expensive.
male biases in disease may be caused by a number of Prolonged energy restriction can lead to immune sup-
factors besides dimorphism in endocrine function. Sev- pression, increasing the risk of infection from oppor-
eral factors such as exposure rates, social and sexual tunistic pathogens (Kramer et al., 1997; Klasing, 1998;
behaviors, habitat, diet, and hormone levels may Lin et al., 1998; Shephard et al., 1998; Ing et al., 2000;
account for some of these differences (Klein, 2000). Koski and Scott, 2001). Likewise, strenuous exercise or
Only a few studies have investigated immune- participation in energetically demanding tasks, such as
endocrine correlates in human males. In a large reproduction, can also compromise immune functions
sample of healthy military men, Granger et al. (2000) (Norris et al., 1994; Richner et al., 1995; Deerenberg
found no association between testosterone and T or et al., 1997; Nordling et al., 1998; Nelson et al., 2002;
B lymphocytes. In contrast, testosterone levels Bonneaud et al., 2003). Changes in metabolism
were positively associated with parasitemia of Plasmo- following infection as well as in vivo assessments of
dium vivax malaria in Honduran men (Muehlenbein energy consumption by the immune system also sug-
et al., 2005). gest that immunocompetence is energetically expen-
Testosterone replacement therapy is currently sive (Newsholme and Newsholme, 1989; Demas et al.,
being evaluated as a means to improve physical 1997, 2003; Lochmiller and Deerenberg, 2000). Resting
metabolic rates increase in infants during upper MALE REPRODUCTIVE ECOLOGY

respiratory tract infections (Fleming et al., 1994), as
Life history theory and reproductive ecology
well as in East African children during acute episodes
of the measles (Duggan et al., 1986). Compared to An organism’s interconnected adaptations for develop-
other species, the energetic costs of mounting an ment, survival and reproduction combine to form its
immune response in adult humans have not been well life history strategy, and its life history traits describe
described, and the clinical medicine and evolutionary age- and size-specific schedules of development, mor-
biology communities would benefit from further clari- tality, and fertility (Stearns, 1992). Life history theory
fication of these costs. is that part of evolutionary ecology which attempts to
explain phenotypic evolution, and the elements of
demography, trade-offs, bet-hedging, lineage-specific
Prostate cancer effects, quantitative genetics, and reaction norms help
The prostate gland surrounds the urethra just below us to explain variation in life history traits and strat-
the bladder. Its primary function is to produce, store, egies between organisms. This suite of methods can be
and secrete a fluid that protects sperm when ejaculated used for studying processes common to all species,
into the vaginal tract. Prostate cancer is now the most including humans.
common malignancy of men in the United States: Reproduction is obviously central to the process of
approximately one in six men will develop malignant evolution. Reproductive physiologies and behaviors
prostate cancer in their lifetime (Crawford, 2003). The are evolved response systems, shaped by natural selec-
incidence of prostate cancer has varied over the past tion to adapt individuals to changing environments.
century, with a significant increase following the wide- This allows for a variable response in which a genotype
spread use of digital rectal examination combined with can produce a range of phenotypes depending on
assays for prostate-specific antigen in the 1980s and environmental conditions (a “reaction norm”). How-
early 1990s (Crawford, 2003). Incidence also varies ever, this phenotypic plasticity is limited through
widely between populations with rates much higher lineage-specific effects (canalization of certain traits)
in industrialized regions than in less developed areas as well as trade-offs (Stearns, 1989). Trade-offs are, in
(Quinn and Babb, 2002), although rates in Asia are fact, central to life history theory, which predicts that
very low compared to the rest of the world (Kurihara selection will act on physiological and behavioral
et al., 1989). Within the United States, African Ameri- mechanisms that efficiently regulate the allocation of
can men have an incidence 60% greater than that of energy and time between general competing functions,
Caucasians (Crawford, 2003; Reddy et al., 2003). specifically reproduction, maintenance (i.e., survival),
There are likely multiple causative factors for and growth (Stearns, 1992; Hill, 1993; Kaplan et al.,
prostate cancer. One risk factor is a high fat diet 2000). Because time and energy used for one purpose
(Whittemore et al., 1995, as evidenced by increased risk cannot be used for another, organisms often face
in Asian populations following immigration into the trade-offs, particularly under conditions of resource
United States and a switch from traditional diets to restriction.
one with greater fat and meat intake (Cook et al., Reproductive physiologies and behaviors therefore
1999). There is also some genetic predisposition to represent compromised adaptations that have been
prostate cancer (Shibata and Whittemore, 1997; designed by natural and sexual selection to maximize
Amundadottir et al., 2006), with at least seven lifetime reproductive success. Suppression of current
inherited susceptibility genes (Simard et al., 2002) reproduction in order to increase the likelihood of suc-
and a number of other somatic gene mutations (Nelson cessful future reproduction should function to maxi-
et al., 2003). mize lifetime reproductive success, particularly in
Although the relationship between lifetime expos- unpredictable and stochastic natural and social envir-
ure to androgens and risk of prostate cancer remains onments (Wasser and Barash, 1983). The trade-off
unclear (Eaton et al., 1999; Hsing, 2001), treatment of between current and future reproduction is a common
prostate enlargement or cancer often involves the use one in iteroparous organisms, as is the trade-off
of androgen suppressors (Anderson, 2003). Testoster- between reproduction and survivorship. Because of
one and dihydrotestosterone bind to prostate cells to this, reproductive physiologies and behaviors are flex-
induce proliferation and thus may contribute to pro- ible and responsive to environmental cues, such as
state carcinoma (Carter et al., 1995). Maintaining high diet, stress, disease, and the availability of mates.
androgen levels would function to increase male repro- The field of reproductive ecology examines the
ductive effort, which would just outweigh the costs of effects of ecological factors on reproductive effort
increased risk of prostate cancer later in life. These within the context of evolutionary and life history the-
physiological trade-offs are central to a modern under- ories (Ellison, 2001). Recent detailed studies of human
standing of male reproductive ecology. female reproductive ecology have clarified how female
fecundity represents an adaptive reaction norm that primates: testosterone levels do not significantly
can respond to changes in energy flux, disease, and decrease in wild male orangutans or chimpanzees
psychological stress (Ellison, 1990, 1994, 2003; Ellison during periods of low food availability (Knott, 1999;
et al., 1993; Jasienska and Ellison, 1998, 2004). No Muller and Wrangham, 2005).
longer viewed by most researchers as pathological, Variation in energy expenditure also appears to
decreased ovarian function in response to ecological have little impact on male reproductive function.
stressors likely represents an adaptive mechanism to Recall that spermatogenesis is relatively insensitive
lower the likelihood of a reproductive outcome if envir- to variation in energy balance. Variation in normal
onmental circumstances are not optimal, allowing the or seasonal workload and exercise also appears to
female to wait and invest in a future reproductive event have little effect on testosterone levels (Ellison and
with a better likelihood of success. Panter-Brick, 1996; Bribiescas, 2001). In fact, energy
Energetic investment in female mammalian repro- expenditure appears to negatively affect testosterone
duction is obviously expensive and very different levels only after long-term high output (Bagatell and
from that of males. Until recently, the study of human Bremner, 1990; Roberts et al., 1993; Gomez-Merino
male physiology has typically been conducted by clin- et al., 2003, 2005). Acute, anabolic exercise can actu-
icians and other medical investigators, not biological ally cause increases in testosterone levels (Cumming
anthropologists or evolutionary biologists. This has et al., 1986).
changed in recent years with increased clarification Depressed testosterone levels can result from acute
of the adaptive functions of male reproductive vari- or chronic exposure to psychological stressors, includ-
ation (Campbell and Leslie, 1995; Bribiescas, 2001; ing skydiving (Chatterton et al., 1997) and military
Muehlenbein and Bribiescas, 2005). training (Gomez-Merino et al., 2003, 2005). These
effects are likely caused by the actions of glucocorti-
coids and endogenous opioids on the hypothalamic-
Causes of variation in male testosterone levels
pituitary-gonadal system. For example, glucocorticoids
There are enormous amounts of variation in hormone like cortisol can directly suppress Leydig cell function
levels within and between men. Moment-to-moment (Gao et al., 2002; Hardy et al., 2005) and downregulate
variation in testosterone level is caused by the pulsatile testicular LH receptors (Aakvaag et al., 1978; Bambino
release of GnRH from the hypothalamus (Spratt et al., and Hsueh, 1981). Glucocorticoids can also suppress
1988). Testosterone production can be influenced the production and secretion of gonadotropins from
by many factors, including genetics (Jameson, 1996; the hypothalamus and pituitary (Doerr and Pirke,
Beranova et al., 2001; Ring et al., 2005) and diet. For 1976; Attardi et al., 1997; Kalantaridou et al., 2004;
example, high alcohol consumption (Muller et al., Mitchell et al., 2005; Breen and Karsch, 2006).
2003), low zinc intake (Abbasi et al., 1980), and a low Endogenous opioids and cytokines can similarly affect
carbohydrate diet (Anderson et al., 1987) may all cause the hypothalamus (Gilbeau and Smith, 1985; Sapolsky
decreased testosterone synthesis, although Key et al. and Krey, 1988; Isseroff et al., 1989; Bonavera et al.,
(1990) and Deslypere and Vermeulen (1984) have 1993; Oktenli et al., 2004).
reported no difference in testosterone levels in omni- These proximate mechanisms, in addition to
vorous versus vegan/vegetarian (low fat) diets. Others others, are also responsible for inhibited reproductive
have suggested low testosterone levels are associated processes, including hypogonadism and hypogonado-
with a low protein diet (Christiansen, 1991b). Obese tropism, following injury, infection and immune acti-
individuals also typically have lower testosterone vation. The degree of response is often associated with
levels, due in part to aromatization of testosterone into the degree of disrupted somatic injury (Spratt et al.,
estrogens in adipose tissue (Kley et al., 1981). However, 1993; Cernak et al., 1997). Some infections can cause
as discussed earlier, relative changes in energy balance direct testicular pathology in humans (Nelson, 1958;
have little effect on male reproductive function. Iturregui-Pagán et al., 1976) in addition to diminished
Testosterone levels may vary according to energy libido (Yirmiya et al., 1995). Men infected with HIV
balance, but only under the most taxing circum- frequently exhibit low testosterone levels, testicular
stances. For example, complete fasting decreases tes- pathology, and azoospermia, possibly through direct
tosterone and hypothalamic-pituitary functioning, infection of the testes and/or hypothalamus-pituitary
although these effects appear to be quickly reversible (Poretsky et al., 1995; Lo and Schambelan, 2001; Dobs
(Klibanski et al., 1981; Röjdmark, 1987; Bergendahl and Brown, 2002). Honduran men infected with Plas-
et al., 1991; Opstad, 1992; Veldhuis et al., 1993). Acute modium vivax exhibit significantly lower testosterone
changes in food availability also do not cause signifi- levels during infection compared to postrecovery
cant changes in testosterone levels in human males samples as well as age-matched healthy controls
(Bentley et al., 1993; Ellison and Panter-Brick, 1996). (Muehlenbein et al., 2005). Similar results have been
Similar results have been identified in nonhuman identified with African sleeping sickness (Trypanosoma
brucei ssp.) (Ikede et al., 1988; Hublart et al., 1990; of Congo (Ellison et al., 1989; Bentley et al., 1993),
Soudan et al., 1992; Reincke et al., 1998), toxoplasmo- !Kung San of Namibia (Worthman and Konner, 1987;
sis (Toxoplasma gondii) (Stahl et al., 1995; Antonios Christiansen, 1991a), Tamang and Kami of Nepal
et al., 2000; Oktenli et al., 2004), filaria (Loa loa and (Ellison and Panter-Brick, 1996), Gainj of New Guinea
Mansonella perstans) (Landsoud-Soukate et al., 1989), (Campbell, 1994), Turkana of Kenya (Campbell et al.,
and schistosomiasis (Saad et al., 1999). 2006), men from Harare, Zimbabwe (Lukas et al., 2004),
and the Okavango Delta of Namibia (Christiansen,
1991b). In fact, testosterone levels are about twice as
Summary of male reproductive ecology
high in North American men compared to other popu-
It is clear that acute immunological and psychological lations around the world, and their range of variation
stress in addition to chronic negative energy balance are in about 10-fold greater. We see a similar pattern in
all potential factors that can affect male testosterone chimpanzees: captive animals with high food abun-
levels. Based on evidence presented throughout this dance throughout their entire lives are characterized
chapter, human male reproductive neuroendocrine by relatively higher testosterone levels compared to
function therefore represents a reaction norm in which natural populations with lower food abundance
a number of factors interact to produce a phenotypic- (Muller and Wrangham, 2005).
ally plastic response to environmental stimuli. The abil- The relative contributions of food availability and
ity to alter testosterone levels in response to stimuli, disease risk in accounting for population variation in
such as availability of resources and/or injury and ill- human testosterone levels are not yet tested. However,
ness, likely represents an adaptive mechanism to aug- it is likely the case that ecological differences exert
ment either male reproductive effort or survivorship. As some developmental effects. Nutritional and immuno-
described above, augmenting mammalian male repro- logical differences during development may play
ductive effort is largely accomplished through elevated important roles in “programming” baseline testoster-
testosterone levels and increased musculoskeletal per- one synthesis and secretion as well as variability in
formance (Bribiescas, 2001), which aids in work cap- later adulthood. Given its interconnected regulatory
acity, intersexual competition, intrasexual coercion, relationship with the reproductive, metabolic, and
and mate choice. Spermatogenesis is energetically inex- immune systems, testosterone levels in adulthood
pensive and relatively insensitive to variation in testos- could then function as an important information trans-
terone levels, whereas musculoskeletal function is ducer, regulating the differential investment in com-
energetically expensive and is under tight physiological peting trade-offs according to the availability of energy
control by androgens. Elevated testosterone levels may (Bribiescas, 2001) and disease risk in the environment
enhance male reproductive effort, but at significant (Muehlenbein, 2008). Like females, human males
metabolic and immunological costs (Bribiescas, maintain some ability to alter the expression of repro-
2001; Muehlenbein and Bribiescas, 2005). These costs ductive hormones, and therefore manage the life his-
likely account for the functional significance of high tory trade-off of reproduction versus survival, in
variability in testosterone levels within and between response to environmental stimuli.
individuals.
In environments characterized by high extrinsic
mortality, unpredictable resources and/or high disease DISCUSSION POINTS
risk (i.e., periods of negative energy balance and
immune activation), depressed testosterone levels and 1. Describe in detail the various aspects of male
muscle atrophy would function to avoid some of the reproductive effort.
metabolic and immunological costs caused by other- 2. What are the costs and benefits of testosterone for
wise higher testosterone levels. In this case, energy males?
would be allocated to processes that maximize survi- 3. How does hormone variation affect sperm production?
vorship, such as adipocyte deposition or immunocom- 4. How is male reproductive ecology different from
petence. In environments characterized by lower that of females?
extrinsic mortality, high access to resources and low 5. Discuss all of the major sources of variation in
disease burden, testosterone levels could be elevated. testosterone levels within and between men.
These hypotheses may explain why, compared to more 6. How would you test the hypothesis that differences
industrialized populations in the United States and in energy availability and disease/injury risk
Europe, testosterone levels are typically lower in for- account for differences in baseline hormone levels
ager, horticultural, and pastoral populations, including and patterns of variation between people and
the Aché of Paraguay (Bribiescas, 1996), Ariaal of populations?
Kenya (Campbell et al., 2003), Aymara of Bolivia (Beall 7. What are some of the primary characteristics of
et al., 1992), Efe and Lese of the Democratic Republic male reproductive senescence?
8. From the standpoint of sexual selection, why Anonymous. (1970). Effects of sexual activity on beard
would some males choose to “enhance” themselves growth in man. Nature, 226, 869–870.
through use of anabolic-androgenic steroid use? Antonios, S. N., Ismail, H. I and Essa, T. (2000). Hypothal-
Why is this a poor decision? amic origin of reproductive failure in chronic experimental
9. Search the World Health Organization website for toxoplasmosis. Journal of Egyptian Society of Parasitology,
30(2), 593–599.
country-specific data on sex differences in mortal-
Anway, M. D., Cupp, A. S., Uzumcu, M., et al. (2005). Epi-
ity rates. In what countries, if any, do men outlive
genetic transgenerational actions of endocrine disruptors
women on average? Why, according to this chap-
and male fertility. Science, 3(308), 1466–1469.
ter, would these men tend to outlive women? Apicella, C. and Marlowe, F. (2004). Perceived mate fidelity
and paternal resemblance predict men’s investment in
children. Evolution and Human Behavior, 25, 371–378.
Arce J. C., De Souza, M. J., Pescatello, L. S., et al. (1993).
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hamadryas baboons, Papio hamadryas. Behavioral Ecology ical characteristics: facts and constructs. European Jour-
and Sociobiology, 35, 175–184. nal of Endocrinology, 144, 183–197.
Zirkin, B. R. and Chen, H. (2000). Regulation of Leydig cell Zuk, M. and McKean, K. A. (1996). Sex differences in para-
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tion, 63, 977–981. nal of Parasitology, 26, 1009–1023.
Part IV
Growth and Development
“Man is an intelligence, not served by, but in servitude

to his organs.”
Aldous Huxley (1894–1963)
377
22 Evolution of Human Growth
Barry Bogin
INTRODUCTION from an undifferentiated or immature state to a highly

organized, specialized, and mature state. Physical matur-
Why should a human evolutionary biologist study ation is measured by functional capacity, for example,
growth of the human body? The reason is because the maturation of bipedal walking results from changes
for multicellular organisms, most major evolutionary with age in skeletal, muscular, and motor skills of the
change proceeds by alterations in the pattern of infant and child. Human growth, development, and mat-
growth, development, and maturation. The human uration have evolved, sometimes as discrete processes,
species is no exception. In this chapter we review both but more often as an integrated series of biological
classic and recent research on the evolution of the events.
human pattern of growth. The major points of this Dobzhansky (1973) said that, “nothing in biology
review are: makes sense except in the light of evolution.” Human
growth, development, and maturation, which follow a
1. Humans have four stages of growth and development
unique pattern among the mammals and, even, the
between birth and adulthood. These are infancy,
primates, are no exceptions to Dobzhansky’s admonition.
childhood, juvenile, and adolescent.
A consideration of the chimpanzee and the human, two
2. The infancy and juvenile stages are shared with most
closely related (genetically) extant primates, shows the
nonhuman primates, social carnivores, elephants,
value of taking an evolutionary perspective on growth.
and many cetaceans. The childhood and adolescence
Huxley (1863) demonstrated many anatomical similar-
stages are human species-specific features.
ities between chimpanzees and humans. By the mid
3. Human childhood and adolescence evolved because
1970s, King and Wilson (1975) established that these
they confer reproductive advantages, increasing the
anatomical similarities are due to a near identity of
fertility of the parents and reducing the mortality of
the structural DNA of the two species. The recent specifi-
their offspring. This is classic natural selection.
cations of both the human and chimpanzee genome
4. Adolescence may have evolved by both natural
show a greater than 99% identity in the coding DNA
selection and sexual selection. Adolescents may
(Shankar et al., 2007). Nevertheless, there are fundamen-
contribute significant amounts of food and labor
tal differences between the chimpanzee and human
to their families and this enhances reproduction by
species in anatomy, including cranial shape, brain size,
the parents and survival of their offspring (natural
and relative length of arms versus legs.
selection). The sex-specific features of adolescent
Variation in the expression of common genetic
girls and boys enhances opportunities for an
sequences by regulatory DNA (Davidson, 2001; Mattick,
apprenticeship-type of learning and practice of
2004), acting in concert with neuroendocrine products
the wide variety of economic, social, political, and
(Finch and Rose, 1995; Cobourne and Sharpe, 2003;
sexual skills needed for their own adulthood and
Shibaguchi et al., 2003), is likely to alter growth rates
successful reproduction (sexual selection).
of shared human–chimpanzee anatomical structures
to produce structural and functional differences. D’Arcy
GROWTH AND EVOLUTION Wentworth Thompson showed in 1917 (Thompson,
1917, 1942) that the differences in form between the
Growth may be defined as a quantitative increase in size adults of various species may be accounted for by
or mass. Measurements of height in centimeters or differences in growth rates from an initially identical –
weight in kilograms indicate how much growth has taken one might better say “similar” – form. Thompson’s
place in a child. Development is defined as a progression transformational grid system (Figure 22.1) for the
of changes, either quantitative or qualitative, that lead growth of the chimpanzee and human skull from birth
379
380 Barry Bogin
species. In this chapter we explore the selective pressures

that appear to have caused ape–human differences
relating to physical growth and development and repro-
ductive success.
EVOLUTION OF HUMAN GROWTH

AND REPRODUCTION
Why the juxtaposition of physical growth with repro-

duction in the heading for this section? As Charles
Darwin so astutely observed, evolution by natural selec-
tion occurs due to differential reproductive success, that
is, differences in fertility and mortality. So, evolution is
dependent on the process of reproduction. Consider the
following. There are about 6.5 billion people alive today
(http://www.census.gov). Our closest evolutionary rela-
22.1. Transformation grids for the chimpanzee (left) and human
tive, the chimpanzee is an endangered species. Indeed
(right) skull during growth. Fetal skull proportions are shown
above for each species. The relative amount of distortion of the total population of great apes – orangutans, gorillas,
the grid lines overlying the adult skull proportions indicate bonobos, and chimpanzees – can be seated in any
the amount of growth of different parts of the skull (inspired modern football stadium. By this or any other measure,
by the transformational grid method of D’Arcy Thompson, 1942, human reproductive success stands in sharp contrast to
and redrawn from Lewin, 1993).
that of almost all other species of nondomesticated
mammals, even nonhuman species of primates.
to maturity, show how both may be derived from a Comparison of human women (Homo sapiens) and
common neonatal form. Different patterns of growth wild-living chimpanzee (Pan troglodytes) females illus-
of the cranial bones, maxilla, and mandible are all that trates the difference in fertility. Women delay the onset
are required to produce the adult differences in skull of reproduction (first birth) to a relatively late age,
shape. Of course, the differences in skull growth are about 19 years on average for a worldwide sample of
related to size and shape of the brain, and size of the human societies (Bogin, 2001). Chimpanzees in the
dentition (both species have the same number and wild have an average age at first birth of 13.1 years of
classes of teeth). In a similar manner, the differences age (Littleton, 2005, based on research at the Gombe,
in the postcranial anatomy between chimpanzee and Mahale, Tai, and Bossou research sites in Africa).
human being result from unequal rates of growth for Chimpanzees continue to reproduce until death, which
common skeletal and muscular elements. usually occurs by 35 years of age (Kaplan et al., 2000).
The evolution of the human pattern of growth may Women end reproduction in their forties, but live for
be understood by the study of growth and development one or more decades after menopause (cessation of
in fossil species and by comparison of growth patterns menstrual cycles subsequent to the loss of ovulation).
in living species, especially the primates. It is now clear Some female chimpanzees in the wild live into their
that no living species of nonhuman primate has all of forties, making their total reproductive life span six to
the characteristics of human growth, in particular eight years longer than women (Gage, 1998). Even so,
the human childhood and adolescent stages of life people can produce as many or more newborns than
(these are defined and discussed below). This strongly chimpanzees in the shorter time. The total fertility rate
suggests that the human pattern could only have (TFR) for wild chimpanzees averages 5.9 offspring
evolved within the taxonomic group of the hominins, a and the TFR human women in rural Costa Rica aver-
group that includes the human species and extinct ages 6.4 (Gage, 1998). Average TFR for human women
forms that were obligated to bipedal locomotion varies by society, but the rural Costa Rica example is
(members of the Genus Homo) or facultatively capable fairly typical of human agricultural-based societies.
of bipedality (e.g., genera such as Australopithecus, The documented maximum offspring production in
Pranthropus, Sahelanthropus, Orronin, etc). Hominin wild chimpanzees is for a high-ranking female named
primates appear by six to seven million years ago in Fifi from the Gombe site. In the year 2003 Fifi, at
Africa. The locomotor, behavioral, ecological, and repro- 44 years of age, became a mother for the 9th time
ductive isolation of Homininae from the Paninae (Goodall, 2003). In 2006 both Fifi and her two-year-old
(chimpanzees, gorillas, bonobos, and their extinct daughter Furaha were reported missing and presumed
ancestors) over the past few million years provides the dead (http://www.janegoodall.org/news). One chimpan-
time depth for the evolutionary differences between zee researcher describes Fifi’s fertility as “exceptional”
Evolution of Human Growth 381
(Dr. Anne Pusey, personal communication). The known fertility populations it is more likely that married
maximum TFR for human societies is for the Hutterites women will reproduce than unmarried women. The
(a religious isolate in Canada) at 9.83 during the time Hutterites are a religious order who prize high fertility
period 1946–1965 (Nonaka et al., 1994; Figure 22.2). of women. They practiced agriculture and were gener-
In contrast with exceptional case of Fifi, the Hutterite ally well-nourished and healthy. Adherents marry after
average is for 1682 Hutterite women of the Dariusleut age 15 years and, traditionally, did not practice any
population of Canada, living in 125 colonies with a total form of birth control. The curve labeled “Henry’s 13”
population of 10 000 individuals (Sato et al., 1994). represents 13 natural fertility small societies studied
The TFR is based on another fertility statistic, the by the French historical demographer Louis Henry
age-specific fertility rate (ASFR). Figure 22.2 illustrates (1961), who first noted the relatively constant shape of
ASFR for captive chimpanzees (Littleton, 2005), for the the age specific fertility rate in different populations.
Hutterites, and several other human societies. The The “Chinese farmers” represent a group of rural
numbers given on the y-axis indicate the number of villagers studied in the 1930s and the “!Kung” are a
births per female of a given age, per year, per 1000 society of hunters and gathers living in the Kalahari
females in the population. The captive chimpanzees desert of Botswana in southern Africa studied in the
reside at the Taronga Zoo in Australia where they have 1960s and 1970s. While the rural Chinese farmers and
been allowed natural breeding (no contraception) for the !Kung are considered to be “natural fertility,” note
the past 50 years. Excellent records by zoo staff ensure that their levels of fertility are lower at all ages than the
the quality of the fertility data. Controlled diets and other two groups. In fact, !Kung and Chinese women
health care allow for optimal fertility of the females. are known to use herbal medicines and other means to
We may assume that the ASFR for these captive chim- prevent or terminate pregnancies. Lower fertility among
panzees represent the near maximum values for the the rural Chinese and the !Kung may also be due to the
species. Estimated ASFR for wild-living chimpanzees stress of inadequate nutrition (Howell, 1979).
average about 25–30% lower than rates for the captive One reason that the Hutterites and “Henry’s 13” have
chimpanzees until age 30 years. After age 30 years the greater ASFRs and greater TFR than chimpanzees is due
ASFRs are similar. to relatively short birth intervals. For Hutterite women
The human groups illustrated in Figure 22.2 are so- the interval between live-births was 22.1 months at
called “natural fertility” populations. These are defined age 30 and 31.2 months at age 40. These intervals
as societies without conscious family size limitations included 6.5 months of postpartum amenorrhea (Larsen
due to contraception or induced abortion. Only married et al., 2003). Women living in other agricultural societies
women are represented in this figure, because in natural may reduce the birth interval to less than 2.0 years, but if
600
550
500
Hutterites
450
Henry’s 13
Age specific fertility rate
400 Chinese farmers

!Kung
350 Chimpanzee, captive
300
250
200
150
100
50
0
7.5 12.5 17.5 22.5 27.5 32.5 37.5 42.5 47.5
Age groups in years
22.2. Age-specific fertility rates (per 1000 females in the population) for captive chimpanzees and for
married women in natural fertility populations. The captive chimpanzee data are from Littleton (2005).
The human data are redrawn from Ellison and O’Rourke (2000).
382 Barry Bogin
the mother is malnourished and/or ill this often has EARLY WEANING AND CHILDHOOD
negative health consequences to the infant and the
mother (Bogin, 2001). In several human forager soci- The relative rapidity and absolutely greater fitness
eties, including the Ache, Hadza, Hiwi, and !Kung, the (survival to adulthood) of human reproduction depends
interval between successful births averages 3.4 years on many factors, and two of the most important are
(40.8 months) for women (Kaplan et al., 2000). The the early weaning of infants, relative to other species,
longer birth interval for these forager women may be and the co-operative social care of children. Human
due to marginal nutrition, heavy physical labor, and infants are fed by lactation, and this is true for all
an extended period of lactation, all of which drain mammalian infants. Mammalian mothers must nurse
energy resources away from ovulation (Ellison and their infants until the young are capable of independent
O’Rourke, 2000). feeding. This usually coincides with the eruption of the
In contrast to these human examples, the interval first permanent molar (M1), which is needed so that
between successful births for wild-living chimpanzee the infant can eat an adult-type diet (Smith, 1991).
females ranges from 5.2 years to 5.6 years at the Gombe The infant must also be able to forage for itself, which
and Mahale research sites in Tanzania (Teleki et al., 1976; usually coincides with M1 eruption in the majority
Goodall, 1983; Nishida et al., 1990). At one of the Kibale of mammalian species. The chimpanzee infant’s M1
Forest research site in Uganda, chimpanzees average erupts at a mean age of 3.1 years (Smith et al., 1994;
7.0 years between successful births (Pusey, 2001). High- Anemone et al., 1996), but the mother continues to
ranking female chimpanzees can reproduce success- nurse for about another 2 years as the infant learns
fully every 4.0 years and have high offspring survival how to acquire and process foods (Pusey, 1983).
(Pusey et al., 1997), but they still lag behind human Because of the chimpanzee infant’s dependency on the
women in both the production of new births. mother, the average period between successful births is
The human advantage in reduced birth intervals delayed relative to M1 eruption.
is compounded by greater survival of the infant to Human infants are weaned early relative to M1
adulthood, when the offspring begin their own repro- eruption, at a median age of 30–36 months in trad-
duction. Typically, only two offspring that a female itional human societies (Dettwyler, 1995) and as early
chimpanzee produces live to adulthood (Pusey, 2001). as 6.5 months in the Hutterites. The human M1 erupts
This means that only about 32% of live-born chimpan- at about six years of age. Even at age six years, human
zee infants survive to maturity (age 15 years). Even in offspring have much to learn before they can survive
captivity the mortality rates for infant and juvenile on their own. The relatively early weaning of human
chimpanzees is high relative to human beings (Little- infants is therefore quite unexpected when compared
ton, 2005). In contrast, more than 50% of live-born with other primates and mammals. However, the short
human infants survive to age 20 years in forager birth interval gives women a distinct advantage over
societies (Kaplan et al., 2000). In agricultural and the apes: women can produce and rear two offspring
industrial societies the rate of human survival is through infancy in the time it takes chimpanzees or
greater, reaching more than 90% in the wealthy orangutans to produce and rear one offspring. The
nations today (Gage, 1998; http://www.census.gov). weaned infant, though, must survive to adulthood if
Human survival to reproductive age is the best of any the short human birth spacing is to result in a true
animal species, and chimpanzee infant survival is the reproductive advantage. How is it possible that human
second best (Bogin, 1999). beings trade-off early weaning for increased reproduct-
The net reproductive result of these contrasts in age ive frequency and still ensure offspring survival?
at reproduction, reproductive life span, birth interval, Short birth intervals entail a compromise between
and infant survival to adulthood is that human beings maternal investments in a current infant and in a
out reproduce chimpanzees. Studies of birth, deaths, future infant. A mother who stops nursing her current
and migrations of chimpanzees find that their popula- infant leaves the infant in the predicament of how to
tions are, at best, stable. Goodall (1983) reports that eat. Human three year olds cannot move on to feeding
between the years 1965 and 1980, 51 births and 49 deaths independence; they cannot forage for themselves. Even
occurred in one community of wild chimpanzees at if they could get hold of food from others, children
the Gombe Stream National Park, Tanzania. During a cannot process the diet of juveniles or adults because
10-year period, Nishida et al. (1990) observed 74 births, of their fragile deciduous dentition and the small size of
74 deaths, 14 immigrations, and 13 emigrations in one the digestive tract (Behar, 1977; Smith et al., 1994).
community at the Mahale Mountains National Park, Sellen (2006) explains that, “. . . digestion of some foods
Tanzania. In contrast, the average annual increase of and absorption of nutrients is constrained by small
the human population is about 1.2%. By some estimates, stomach size and short intestinal length throughout
the world population will reach nine billion people by childhood (Hamosh, 1995)” – meaning until seven
the year 2050 (Bogin, 2001). years of age.
2000 system of the child. Essentially the diet for a weaned

three year old must consist of what we call today “baby
Homo foods.” Human mothers, however, do not have to
provide 100% of nutrition and care directly to their
Brain mass 1500
(g) children. Because they are weaned, dependent children
may be fed and protected by any older individuals in the
700
social group. Indeed, traditional societies deal with the
600 1000
500
problem of childcare by spreading the responsibility
400 among many individuals, including older juveniles,
300
Pan adolescents, grandmothers, and other adults.
200 500 Co-operative childcare seems to be a human uni-
100
versal (Hrdy, 1999). For example, in Hadza society
0
(African hunters and gatherers), grandmothers and
0 great aunts supply a significant amount of food and
0 5 10 15 20 25 30
care to children (Hawkes et al., 1997; Blurton Jones,
Age (years)
2006). In Agta society (Philippine hunter-gatherers),
22.3. Brain-mass growth data for humans (Homo sapiens) and
women hunt large game animals but still retain primary
chimpanzees (Pan troglodytes). Brain mass increases during the
postnatal period in both species. Lines represent best-fit Lowess responsibility for childcare (Estioko-Griffin, 1986). They
regressions through the data points. “M”, males; “F”, females; accomplish this dual task by living in extended family
“U”, sex unidentified (Vrba 1998). The human regressions separ- groups – two or three brothers and sisters, their spouses,
ate into male (upper) and female (lower) curves. The inset shows children, and parents – and sharing the childcare.
brain-mass growth for each species during the first postnatal year.
Among the Maya of Guatemala (horticulturists and agri-
Reproduced from Leigh (2004) with kind permission of the author.
culturists), many people live together in extended family
compounds. Women of all ages work together in food
Another biological constraint on children is that preparation, clothing manufacture, and childcare
they have relatively large, fast-growing brains that are (Bogin field notes, 1988–1993; Figure 22.4). In some
energy demanding. Infancy and childhood are the societies including the Agta and the Aka pygmies,
times of the most rapid, postnatal brain growth in hunter-gatherers of central Africa (Hewlett, 1991),
human beings. The high rate of brain growth is ener- fathers provide significant childcare.
getically expensive. The human newborn uses 87% of Death of the chimpanzee mother almost always
its resting metabolic rate (RMR) for brain growth and results in death of her infant. This is because chimpan-
function. By the age of 5 years, the percent of RMR zee females usually provide 100% of infant care to their
usage is still high, at 44%, whereas in the adult human, offspring (Tutin, 1994). Moreover, female chimpanzees
the figure is between 20 and 25% of RMR. At birth, are generally in competition with each other for
chimpanzees have smaller brains than humans, and access to critical resources and antagonistic toward
the difference in size between the species increases each other and each others offspring. Adoptions of
rapidly (Leigh, 2004, Figure 22.3). Consequently, the orphaned infants do occur occasionally in chimpanzee
RMR values for the chimpanzee are only about 45% social groups, but only infants that are older than four
at birth, 20% at age 5 years, and 9% at adulthood years and able to forage for themselves survive more
(Leonard and Robertson, 1994). than a few weeks (Goodall, 1983; Tutin, 1994). Goodall
Several studies of human forager societies show that noted deterioration in the health and behavior of infant
children cannot produce enough food to meet their chimpanzees whose mothers had died. The behavioral
energy and nutrient needs. Indeed, food production changes include symptoms of clinical depression, such
remains below food requirements until age 15–20 years as listlessness, whimpering, refusing to eat or interact
in these societies (Kaplan et al., 2000; Kramer, 2002; with others, and less play. Health changes, such as loss
Gurven and Walker, 2006; Robinson et al., 2008). of weight, were observed. Goodall reported that even
those older infants who survived the death of their
mothers were affected by delays in physical growth
CO-OPERATIVE CHILD CARE IN HUMAN and maturation.
SOCIETIES Because of human co-operative care and kinship
organization, family members may adopt orphaned
The child, then, needs to be supplied with foods. These infants and children. It is well known that human infants
foods need to be specially chosen and prepared so that and children also show physical and behavioral path-
they are easy to chew and swallow because of the small ology after the death of one or both parents (Bowlby,
and fragile deciduous teeth of the child. The foods 1969). Humans, however, usually overcome this and
also must be nutrient dense due to the small digestive both survive and thrive under the care of adoptive
384 Barry Bogin
22.4. Co-operative care of children by women

and juvenile girls. The example is from the
Kaqchikel-speaking Maya region of Guatemala.
The women perform household and food prep-
aration duties while the juvenile girls play with
and care for the children. Photograph by Barry
Bogin.
parents. It seems that the human infant and child can growth, or distance, and rate of growth, or velocity,
more easily make new attachments to other caretakers of healthy human beings from birth until adulthood.
than can the chimpanzee infant (Chisholm, 1999). The The velocity changes in growth correspond with stages
ability of a variety of human caretakers to attach to one of human life history.
or several human infants may also be an important The infancy stage begins at birth and lasts until
factor. The psychological and social roots of this differ- about 3.0 years of age. Postnatal infant growth is rapid,
ence between human and nonhuman species in attach- as is its rate of deceleration. Human childhood encom-
ment behavior are not well understood. The flexibility in passes the ages of about 3.0–7.0 years. Body growth
attachment behavior evolved by hominin ancestors may during childhood proceeds at a steady rate of 5–6 cm
have contributed, in part, to the evolution of childhood per year. Brain growth is rapid and the difference in
and the reproductive efficiency of the human species. growth rates is an example of a life history trade-off
Summarizing the data from many human societies, given limited energy. Many children experience a tran-
Lancaster and Lancaster (1983) call this kind of co- sient and small “spurt” in growth rate as they transition
operative childcare and feeding “the hominid adapta- into the juvenile period. Juvenile mammals are sexually
tion” because no other primate or mammal does all immature, but physically and mentally capable of
of this. The evolutionary reward is that by reducing the providing for much of their own care. In many human
length of the infancy stage of life (i.e., shortening the societies, juveniles perform important work including
period of lactation) and by developing the special fea- food production and the care of children (i.e. “babysit-
tures of the human childhood stage (i.e., flexibility in ting”). Juvenile growth rate declines until puberty,
attachment), humans have the potential for greater life- representing another trade-off between current growth
time fertility than any ape. versus building a higher quality body and behavioral
repertoire over a longer period of time. Puberty is a
short-term event of the central nervous system, which
LIFE HISTORY THEORY initiates sexual maturation and the adolescent life stage.
In humans, the hormones responsible for sexual matur-
How did human beings come to have this unusual fer- ation also cause the adolescent growth spurt in stature
tility and co-operative childcare? Life history theory is and other skeletal dimensions. The growth spurt, which
the study of the evolution and function of life stages and is a notable feature of the adolescent growth stage, but
behaviors related to these stages (Stearns, 1992). The not the only defining characteristic, begins at about 10.0
life history of a species may be defined as the evolution- years for girls and 12.0 for boys. The adolescent spurt
ary adaptations used to allocate limited resources and and growth of the skeleton ends at about 18–19 years for
energy toward growth, maintenance, reproduction, rais- girls and 20–22 years for boys, and with this the adult-
ing offspring to independence, and avoiding death. Life hood, or reproductive stage of life history, begins.
history patterns of species are often a series of trade-offs There are also significant changes in dentition, motor
between growth versus reproduction, quantity versus control, muscular development, cognitive function, and
quality of offspring, and possibilities given limited time emotions associated with human infancy, childhood,
and resources. Figure 22.5 illustrates the amount of juvenile, and adolescent development. The integration
20 200
18
180
16
160
Height velocity (cm / year)

14
12 140
Height (cm)
10 120
I
8
100
6
C 80
4
J A
2 W M
60
0 40
0 2 4 6 8 10 12 14 16 18 20 22
Age (years)
22.5. Average velocity and distance curves of growth in height for healthy girls (dashed lines) and
boys (solid lines), showing the postnatal stages of human growth. Values for the distance curves are on
the left y-axis; values for the velocity curve are on the right y-axis. In the velocity curves, note the
spurts in growth rate at mid-childhood and adolescence for both girls and boys. The postnatal
stages: I, infancy; C, childhood; J, juvenile; A, adolescence; M, mature adult. In traditional human
societies, weaning (W) of infants from any breastfeeding occurs at an average age of 30 months, with a
range of 6–60 or more months (Dettwyler 1995; Sellen 2006). Figure based on Bogin (1999).
of these separate domains of function also takes place while still in the juvenile stage of our ancestors. Neoteny
with age and maturation. These have been much studied implies that human beings are, in a sense, “permanent
by developmental biologists, psychologists and others, children.” Another version of heterochrony suggests the
but only a few key features of human childhood and opposite, which is that human beings, and childhood,
adolescence are discussed below (Bogin, 1999 provides evolved by extending the developmental stages of our
further discussion and references). ancestors. Childhood, in this view, is just a prolongation
of infancy (Bogin, 1997 critiques these notions).
The evolutionary evidence, however, favors the
THE EVOLUTION OF HUMAN CHILDHOOD hypothesis that childhood evolved as a new stage in
hominin life history (hominins or hominids are living
The origins of human childhood have fascinated scholars humans and our bipedal ancestors), first appearing
from many disciplines. Some researchers argue that about two million years ago, during the time of Homo
childhood is an invention of recent human societies. habilis (Thompson et al., 2003). Darwinian evolution
Philippe Ariès (1965) proposed that the concept of child- proceeds by adaptations that increase the fertility of
hood came into existence in sixteenth-century Europe. adults and decrease the mortality of offspring prior
Prior to that time, youngsters were considered to be to their own reproductive age. As explained above, the
“miniature adults,” meaning that once weaned, and less evolutionary value of childhood is that it allows a woman
dependent on their mother, children entered the adult to give birth to new offspring while allowing her existing
world of work. Children were thought to have adult-like dependent offspring to receive care and feeding from
understanding of the physical and social world, an idea close kin and other members of the social group. With
that was overturned with the developmental psychology this assistance, human women may reproduce every
studies of Piaget (1954). three years without sacrificing the health or life of their
A biological hypothesis for human childhood is that previous offspring.
the human patterns of growth and development evolved This type of co-operative breeding is found in some
by heterochrony, an evolutionary process that alters the species of birds and other mammals (e.g., wolves and
timing of growth stages from ancestors to their descend- hyenas) and it works to increase net reproductive
ants. An early twentieth-century version of heterochrony output (Bergmuller et al., 2007). In those species, and
claimed that human childhood evolved by neoteny, in many but not all human groups, the co-operative
meaning that human beings become sexually mature breeders are close genetic relatives of the mother
386 Barry Bogin
(Clutton-Brock, 2002). By assisting the mother to care Several recent ethnographic studies with traditional
for her offspring, the helpers increase their own inclusive societies in various parts of the world show that it
fitness, meaning that they help to ensure that their gen- does not take extra time to learn the intricacies of
etic kin survive to reproductive age (Hawkes et al., 1998; food production (Bock and Sellen, 2002). However, net
Hawkes and Paine, 2006). positive returns on food production, meaning more food
Human societies define kinship relations on the energy produced than consumed, occur only after age
basis of genetic and social ties. Humans are the only 10 years for girls in rural Bangladesh (Robinson et al.,
species to use language and the cultural institution of 2008) and more often only after age 15 years in other
marriage to define kinship categories. The overarching traditional societies (Kaplan et al., 2000; Kramer, 2002).
importance of kinship for the human species is that in Other research finds that mastery of language and the
traditional societies (foragers, horticulturalist, pastor- skills of social competition and mating do require nearly
alists, and preindustrial agriculturalists), kinship is the 20 years (Locke and Bogin, 2006). Perhaps it is best to
central organizing principle for economic production, state that the embodied capital hypothesis for prolonged
social organization, and ideology (e.g., moral codes, human brain growth and complex learning cannot
religious behavior). Industrial Western societies make account for the initial selective impetus for the evolution
use of fictive kinship, the application of kinship names of childhood. Greater embodied capital may be a seco-
to people unrelated by marriage or descent, to enhance ndary benefit of childhood.
social relations, including rights and responsibilities The primary benefit of the evolution of the childhood
towards each others offspring. An example is calling stage of human life history seems to be the reproductive
the close friend of one’s mother by the name “Aunt Maria” advantages to the mother and her close genetic and
instead of Mrs. Smith. “Aunt Maria” may provide food, social kin. The result of the human type of reproduction,
supervision, protection, gifts, and other types of parental with childhood and biocultural co-operative breeding,
investment to her “niece” and the “niece” is expected to means that human woman can successfully produce
behave in accordance with the rules of interaction two infants in the time it takes a chimpanzee to produce
between family members. Human co-operative breeding, one. The investments in childcare by family members
therefore, is biocultural in nature – explained by both translate into higher survival for human children than
genetic and fictive kinship. Human biocultural co- for the, generally, unassisted chimpanzee juvenile. In
operative breeding enhances the social, economic, polit- modern humans, the childhood stage, along with much
ical, religious, and ideological “fitness” of the group as embodied capital, results in the potential for more rapid
much or more than it contributes to genetic fitness. reproduction, the greatest survival to adulthood, and
greater longevity than any other primate species.
CHILDHOOD AND LEARNING

JUVENILE TO ADOLESCENT
Another explanation for childhood is called the
“embodied capital hypothesis” (Kaplan et al., 2000; Following the childhood life history stage the individual
see Chapter 26 of this volume). By “capital” these enters the juvenile stage, which may be defined as the
authors mean both the quality of the human physical time from about 7–10 years old for girls and 7–12 years
body in terms of strength, skill, immune function, and old for boys. It is a stage of slowing growth rate prior to
co-ordination as well as the size and quality of the the onset of sexual maturation (Figure 22.5). Juveniles
brain in terms of knowledge, social networks, strat- have sufficient maturity of many body systems, such as
egies for resource acquisition, mating competition, the dental, locomotor, and cognitive systems, to allow
parenting style, and social dominance. for self-feeding capability. Much important learning of
Observations of nonhuman primates, elephants, economic and social skills takes place during the juven-
social carnivores, and other mammals show that all ile stage. Juvenility ends with puberty, which is an event
of the feeding, social, and reproductive behavior they of short duration (days or a few weeks) that takes place
need to learn and practice can be accomplished during in the brain, within or near the hypothalamic-pituitary
their infant and juvenile stages of life (Pereira and axis, and results in a reactivation within the central
Fairbanks, 1993). Human beings have more to learn, nervous system of sexual development. This includes a
such as symbolic language, kinship systems, and the dramatic increase in secretion of sex hormones, which
use of complex technology. The embodied capital is one marker of the onset of adolescence.
hypothesis suggests that it may require 20 years or The adolescent life history stage of growth, develop-
more to develop the brain and body needed to acquire ment, and maturation lasts 5–10 years after the onset of
it all. Human childhood may have coevolved with puberty: Other notable features of adolescence include
these behavioral complexes to provide the extra time a growth spurt in height and weight, the completion
needed. of permanent tooth eruption, development of secondary
sexual characteristics (fat and muscle typical of each primates has a human-like adolescent growth spurt, nor
sex), and the intensification of interest in and practice many of the other biological and behavioral features
of adult social, economic, and sexual activities leading of the human adolescent stage of life history (Hamada
to sociosexual maturation. Adolescence ends with the and Udono, 2002; Bogin, 2006; but see Leigh, 2001
cessation of skeletal growth in length (the closing of for evidence of growth spurts in body weight). Clearly,
the epiphyses of the long bones), the completion of a juvenile primate does not need to pass through a
dental development (eruption of the third molar, if it is lengthy period of adolescence, with apprenticeship type
present), and sexual maturation (measured for women learning, just to be reproductively successful.
as the age at first reproduction). On a worldwide basis, What factors, then, could give rise to adolescence and
including living and historical societies, the age of further delays in reproduction. The answer, it seems, lies
onset of adulthood averages 19 years for women and in a combination of natural selection for the type of
21–25 years for men (Bogin, 2001). biocultural co-operative breeding that characterizes
human beings and sexual selection. Darwin proposed
sexual selection as an independent and complementary
ADOLESCENCE AS APPRENTICESHIP process to natural selection. Sexual selection was defined
by Darwin as an evolutionary process in animals that,
Some life history theorists hypothesize that an the ado- “. . . depends on the advantage which certain individuals
lescent stage of human growth evolved to provide the have over other individuals of the same sex and species,
time to learn and practice complex economic, social, in exclusive relation to reproduction” (Darwin, 1871,
and sexual skills required for effective food production vol. 1, p. 276). Today we would replace the word repro-
and reproduction and parenting (reviewed in Bogin, duction with mating, as not all mating opportunities are
1993, 1999; also see Chapter 26 of this volume). In this intended to result in a pregnancy. Darwin also wrote that:
perspective, adolescence is a time for an apprenticeship,
working and learning alongside older and more experi- There are many other structures and instincts which must have
enced members of the social group. The benefits of the been developed through sexual selection – such as the weapons
of offence and the means of defence possessed by the males for
skills acquired during adolescence are lower mortality of
fighting with and driving away their rivals – their courage and
both first-time mothers and their offspring. This places
pugnacity – their ornaments of many kinds – their organs for
the “apprenticeship hypothesis” for the learning and producing vocal or instrumental music – and their glands for
practice value of adolescence firmly within Darwinian emitting odours; most of these latter structures serving only to
natural selection theory. There is much human ethno- allure or excite the female (Darwin 1871, vol. 1, pp. 257–258).
graphic and demographic evidence to support the
apprenticeship hypothesis and it is likely that the learn- It is known today that sexual selection also works for
ing and practice of adult skills play an important role in females, meaning that female specific physical and
human growth, development and maturation. behavioral traits may evolve via competition between
However, apprenticeship cannot be the primary the females for mating opportunities with males.
cause for the evolution of adolescence. Learning for
childcare is an example. The ethnographic literature
documents that in human societies juvenile girls often NATURAL SELECTION FOR ADOLESCENCE
are expected to provide significant amounts of child-
care for their younger siblings (Weisner, 1987, 1996). The natural selection case for adolescence is derived
Human girls enter adolescence with considerable from the fact that the evolution of childhood afforded
knowledge of the needs of young children. Learning hominid females the opportunity to give birth at
about childcare, then, is not the reason why human shorter intervals. Producing offspring, however, is only
girls experience adolescence. a small part of reproductive fitness. Rearing the young
Just as childhood evolved so that the mother could to their own reproductive maturity is a surer indicator
resume reproduction more quickly, adolescence is likely of success. Studies of yellow baboons (Altmann, 1980),
to have evolved as a reproductive adaptation for older toque macaques (Dittus, 1977), and chimpanzees (Tel-
individuals. The reason for this is that natural selection eki et al., 1976) show that between 50% and 60% of
works on differential fertility and differential mortality first-born offspring die in infancy. By contrast, in
between individuals. An additional 5–10 years of infertil- hunter-gatherer human societies, such as the Hadza
ity associated with adolescence could not evolve for of eastern Africa, 39% of offspring die in infancy (Blur-
all humans, since those individuals who “cheated” by ton Jones et al., 1992). For the !Kung of southern Africa
terminating growth at an earlier age would begin repro- the figure is 44% (Howell, 1979). Just for comparison,
ducing sooner and would be at a reproductive advantage. it may be noted that in the United States, in the year
All other primates do, in fact, begin reproducing at 1960, about 2.5% of all live, first-born children died
earlier ages than humans, and none of the nonhuman before the age of 1 year (Vavra and Querec, 1973).
388 Barry Bogin
The infants of nonhuman primates are fed and achieve all of these needs. The adolescent growth spurt
cared for by either the mother or, in a few species, the serves as a signal of maturation. Early in the spurt,
father and other close kin. As was mentioned earlier, before peak height velocity is reached, girls develop
infant and childcare in human societies is different pubic hair and fat deposits on breasts, buttocks, and
because many members of the social group provide care thighs. They appear to be maturing sexually. About a
and protection. The contribution of food and other year after peak height velocity, girls experience
resources by many group members helps to insure menarche, an unambiguous external signal of internal
infant survival. reproductive system development.
Kaplan et al. (2000) have documented on the number These changes give adolescent girls the physical
of calories of food produced by juveniles, adolescents, characteristics they need to appear adult-like and enter
and adults in several human foraging societies (Ache, the sociosexual world of adults. The adolescent gains
Hiwi, !Kung, and Hadza). Kramer (2002) performed a skill in economic productivity and some proficiency in
similar analysis for a village of traditional Maya horticul- sexual politics because they look mature sexually, and
turalists in the Yucatan, Mexico, and Robinson et al. are treated as such, several years before they actually
(2008) did the same for Bangladeshi children, juveniles, become fertile. Most adolescent girls experience one to
adolescents, and adults in a traditional farming village. three years of anovulatory menstrual cycles after menar-
These studies show that rates of food production increase che. Nevertheless, the dramatic changes of adolescence
most steeply after age 15 years, that is, in mid adoles- stimulate both the girls and the adults around them to
cence. While adolescent rates of energy production fall participate in adult social, sexual, and economic behav-
well below those of men and women over 20 years of age, ior. For the postmenarchial adolescent girl, this partici-
they are still significant and by age 15 years average pation is “risk free” in terms of pregnancy for several
between 1500 and 2000 kcal per day. That is nearly years. Even after ovulation begins it takes about 5 years
enough energy to meet the needs of the adolescents, for the adolescent to achieve the adult frequency of
which means that these adolescents are no longer a drain monthly ovulations, which is defined as 65% of men-
on older individuals. Extra food foraged by older people strual cycles (Worthman, 1993). This means that if
can be shared with still dependent infants, children, and menarche occurs between ages 12 and 13 years (as is
juveniles. This helps to ensure the survival of the depend- the case for well-nourished populations) the typical
ent young. In reality, of course, the foods gathered by healthy and sexually active adolescent has a reduced
adolescents may be combined with those foraged and possibility of becoming pregnant until she is 17–18 years
hunted by adults, so that all members of the group receive old. Indeed the worldwide median age at first birth is
a balanced diet. The main point to stress, however, is that 19 years (Bogin, 2001).
adolescents contribute to the reproductive success for Although adolescents younger than 17 years old can
their parents and other close kin. The net reproductive and do have babies, both the teenage mothers and the
gain from this co-operative breeding may offset the repro- infants are at risk because of the reproductive immatur-
ductive loss to the individual adolescent who must delay ity of the mother. Risks include a low-birthweight infant,
her own first birth by several more years. However, premature birth, high blood pressure in the mother, and
this still does not rule out “cheating” by reproducing at death for the fetus, the mother, or both. Much of the
age 13 years rather than at 19 years or later. As will be reason for these risks is that adolescent girls are still
explained below, such “cheating” has harmful conse- growing and competing for resources against their own
quences for the young mother and her infant, and this fetus. The likelihood of these risks declines and the
maintains natural selection for the average age at first chance of successful pregnancy and birth increases
birth at 19 years. markedly after age 18. There is, therefore, considerable
natural selection pressure working in concert with the
sexual selection for the adolescent female phenotype
SEXUAL SELECTION FOR ADOLESCENCE of sexual maturity combined with infertility to delay
pregnancy until the end of adolescence.
There is still much the adolescent girl needs to acquire
in order to negotiate adult life besides caring for
infants. She must gain physical size, strength, and UNUSUAL GROWTH OF THE HUMAN PELVIS
fat stores to support pregnancy and lactation. She
must attain proficiency in economic productivity. A fundamental feature of human growth that delays
Finally, she must learn and practice skills in social co- female fertility until the late teenage years is the growth
operation–competition and in sexual politics if she is to of the pelvis. Ellison (1982) and Worthman (1993) found
successfully contend with other women for desirable that age at menarche is best predicted by bi-iliac width,
mating opportunities. The pattern of physical growth the distance between the iliac crests of the pelvis.
and development during adolescence allows girls to A median width of 24 cm is needed for menarche in
American girls living in Berkeley, California, Kikuyu as more physically mature than they in fact are. Grafted
girls of East Africa, and Bundi girls of highland New onto this biological delay in fertility is the embodied
Guinea. The pelvic width constant occurs at different capital that comes from learning and practicing impor-
ages in these three cultures, about 13, 16, and 17 years tant adult sexual, social, economic, and political behav-
old, respectively. The later ages for menarche are due to iors that lead to increase reproductive fitness in later life.
chronic malnutrition and disease in Kenya and Bundi.
Moerman (1982, now known as Marquisa LaVelle)
also reported a special human relationship between SEXUAL DEVELOPMENT IN HUMANS
growth in pelvic size and reproductive maturation. She AND CHIMPANZEES
found that the crucial variable for successful first birth is
size of the pelvic inlet, the bony opening of the birth canal. Some features of the sequence of adolescent events for
Moerman measured pelvic X-rays from a longitudinal girls described above are illustrated in Figure 22.6. The
sample of healthy, well-nourished American girls who human female pattern of physical, behavioral, and
achieved menarche between 12 and 13 years. These girls sexual development after puberty is quite different from
did not attain adult pelvic inlet size until 17–18 years of our closest cousin, the chimpanzee. A key difference is
age. Quite unexpectedly, the adolescent growth spurt, that chimpanzee females have an estrus cycle, not a
which occurs before menarche, does not influence the menstrual cycle. Chimpanzee females advertise their
size of the pelvis in the same way as the rest of the fertility via anogenital swelling. In the wild, females
skeleton. Rather, the female pelvis has its own slow have their first “small irregular swellings of the clitoris
pattern of growth, which continues for several years after between eight and nine years” (Pusey, 1990, p. 208). The
adult stature is achieved. swellings enlarge with time and by about 11 years of age
Why the pelvis follows this unusual pattern of they have their first swelling that is clearly visible to all
growth is not clearly understood. Perhaps bipedal members of the social group (Wallis, 1997). At this
walking, another special human attribute, is a factor. point, adult males show sexual interest in the females
Bipedalism is known to have changed the shape of the when they are swollen (Pusey, 1990). Menarche takes
human pelvis from the basic ape-like shape. Apes have place a few months after the first mature swelling cycle,
a cylindrical-shaped pelvis, but humans have a bowl- and ovulation does not occur for an average of two years
shaped pelvis. The human shape is more efficient for after menarche, although the range of variation is five
bipedal locomotion but less efficient for reproduction months to three years (Pusey, 1990).
because it restricts the size of the birth canal. Human Once female chimpanzees achieve mature estrus
women may need a longer period of pelvic growth to cycles they swell for 13 of the 36 days of their cycle
compensate for the restriction. Whatever the reason, (Pusey, 2001). Ovulation occurs near the end of the swell-
cross-cultural studies of reproductive behavior shows ing period. Male chimpanzees seem to calibrate their
that human societies acknowledge (consciously or not) sexual interest in the females based on the phases of
this special pattern of pelvic growth. Marriage, a estrus, and the most dominant males concentrate their
uniquely human cultural behavior, usually precedes first reproductive efforts toward the likely time of ovulation
childbirth. Age at marriage clusters around 18 years (Goodall, 1986).
for women from such diverse cultures as the Ache Human adolescent girls and adult women have no
of Paraguay, the Hadza of Tanzania, the !Kung of anogenital swellings. While human breast development
Botswana, the Kikuyu of Kenya, Mayans of Guatemala, and menstrual bleeding may be signs of impending
Copper Eskimos of Canada, and both the colonial and fertility, they are not tightly correlated with the onset
early twentieth-century United States (Bogin, 1999; of ovulation or the timing of ovulation during the men-
Kaplan et al., 2000). strual cycle. Even in mature women, the exact timing of
Extra widening of the pelvic inlet late in adoles- human ovulation is “hidden” from other members of the
cence may assist successful birth for human women. social group. Women are often are not certain of their
But, even with this widening human births are diffi- own ovulation (at least in the United States where books
cult. In virtually all cultures older, experienced women to help women time their ovulatory cycles are “best
assist the mother to deliver her infant (Trevathan, sellers”). As a probable consequence of this uncertainty,
1987, 1996). This assistance by both biological and human males show sexual interest in women during
social kinswomen is another example of biocultural most phases of the menstrual cycle. In some cultures,
co-operative breeding in the human species. sexual relations are prohibited during and just after
The special human pattern of pelvic growth helps menstruation, but these are the least likely times for
explain the delay from menarche to full reproductive ovulation.
maturity. That time of waiting seems to be the result There are other important differences, and a few simi-
of both natural and sexual selection and provides the larities, between people and chimpanzees in sociosexual
adolescent girls with many opportunities to be perceived development. Female chimpanzees remain in their natal
390 Barry Bogin
22
20
18
nce
16 sce
ole
Ad
Age (y ears )
14
12
10
8
ood
6 ildh
Ch
4
2
0
Infancy/B.I. Molar 1 Menarche 1st birth
Hominoid developmental landmarks
Orang Gorilla Chimp Human
22.6. Hominoid female developmental landmarks. Data based on observations of wild-living individ-
uals of the ape species Pongo pygmaeus (labeled “Orang”); Gorilla gorilla (labeled “Gorilla”);
Pan troglodytes (labeled “Chimp”); and Homo sapiens (labeled “human”). For humans, the data
comprise healthy individuals from various cultures. The label “Infancy/B.I.” is the period of depend-
ency on the mother for survival, usually coincident with the mean age at weaning and/or a new birth
(“B.I.” means “birth interval”); “Molar 1” is the mean age at eruption of the first permanent molar;
“Menarche” is the mean age at first estrus or menstrual bleeding; “1st birth” is the mean age of
females at first offspring delivery. The label “Childhood” denotes the period of time of human life
history from about age 3.0 to 6.0 years between age at weaning and age of eruption of the first
permanent molar. Childhood “fills the gap” between feeding by lactation and semi-independent
feeding of the juvenile life history stage (maturation of dention, motor skills, and cognitive behaviors
required for self-feeding). The label “Adolescence” denotes the period of time of human female life
history from menarche to adulthood (first reproduction). In a strict biological sense, adolescence
begins at puberty, which takes place two to three years before menarche. However, many human
societies ascribe special biocultural meaning to menarche, including rites of passage from “girlhood”
to “womanhood.” The biocultural events surrounding menarache and the years following it assist girls
to become women in the economic, social, and reproductive spheres of life. Similar rites of passage
are reserved for boys and are tied to biolcultural events of their growth, development, and maturation
(e.g., the adolescent growth spurt, growth of the penis and pubic hair, development of greater muscle
mass). Figure modified from Bogin (1999).
social group until they begin estrus cycles. As they behaviors. Human cultural behavior is more complex and
cycle, the young females leave their natal groups to copu- varied than the social behavior of chimpanzee commu-
late with males from neighboring groups. These visits nities. A final comparison is that human pregnancy
eventually lead to permanent emigration to a new group. usually terminates menstrual cycling; however, a single
Once pregnant the female chimpanzee continues to menstruation (as opposed to “spotting” and pathological
have one or two estrus cycles and many copulations bleeding) following fertilization can occur if the preg-
(Pusey, 2001). Human women may or may not emigrate nancy takes place close to the expected start of the next
from their natal group. An analysis based on the “World period. As for chimpanzees, copulation may continue
Ethnographic Sample” database (Ember et al., 2002) during pregnancy.
shows that 15% of human societies are matrilocal
(married couple resides with the wife’s social group), 4%
are avunculocal (living near or with the wife’s mother’s ADOLESCENCE IS ONLY FOR HUMANS
brother), 67% are patrilocal (couple resides with the
husband’s group), 7% are bilocal (living with either The sexual development of human adolescent girls often
the bride’s or groom’s family) and 5% are neolocal is associated with a series of sociocultural events that are
(married couple establish an independent residence). not reported for any other species. Breast development
In this respect and many others, human societies follow and menarche may promote rites of passage, that is,
cultural rules of behavior that work with and against initiation ceremonies or events that mark the transition
biology to produce a myriad of sexual and reproductive between girlhood and womanhood. This transition often
takes years to complete. Even when marriage takes development, and economic productivity, the 13-year-old
place before or near the time of menarche it may take boy is still more a juvenile than an adult. Anthropologists
years until the bride makes a complete transference from working in many diverse cultural settings report that
her natal family to live with her husband. A detailed few women (and more important from a cross-cultural
description of the variety and significance of human rites perspective, few prospective in-laws) view the teenage
of passage is beyond the scope of this chapter. Interested boy as a biologically, economically, and socially viable
readers may consult the extensive ethnographic litera- husband and father.
ture (e.g., Schlegel and Barry, 1991; Schlegel, 1995). The delay between sperm production and repro-
The physiological, anatomical, growth, developmen- ductive maturity is not wasted time in either a biological
tal, maturational, and behavioral differences between or social sense. The obvious and the subtle psycho-
people and chimpanzees lead to the conclusion that physiological effects of testosterone and other androgen
chimpanzees do not have adolescence. Some time after hormones that are released after gonadal maturation
the divergence from their common ancestor, chimpan- may “prime” boys to be receptive to their future roles
zees and humans evolved different life history patterns as men. Alternatively, it is possible that physical
for sexual development. Physiologically, chimpanzee changes provoked by the endocrines, such as deepening
females seem to have evolved estrus swelling as something of the voice and appearance of pubic hair, provide a
new, because gibbons and orangutans do not have them social stimulus toward adult behaviors. The following
(de Waal, 2001). Human females evolved permanent is an example of the interaction between biology and
breasts, the adolescent growth spurt, and menarche behavior. In 2001, a research team measured and inter-
followed by hidden ovulation as a unique set of traits. viewed Portuguese and Cape Verde boys, ages 10–15
years old, living near Lisbon, Portugal (Bogin and
Varela Silva, 2003). We assessed pubic hair development
WHY DO BOYS HAVE ADOLESCENCE? and voice “breaking.” The older, more mature boys told
us that in school they “speak and act like men” because
Natural and sexual selection for adolescence applies they have pubic hair, but at home they speak like boys to
to both girls and boys. The forces of natural selection show respect for their parents and older siblings. Such
are the same for both sexes but the particulars of sexual are the social pressures of male adolescence!
selection are different. The adolescent development of Whether the influences are primarily physical or
boys is quite distinct from that of girls. Boys become social, early in adolescence, sociosexual feelings
fertile well before they assume the size and the physical including guilt, anxiety, pleasure, and pride intensify.
characteristics of men. Analysis of urine samples from At the same time, adolescent boys become more inter-
boys 11–16 years old show that they begin producing ested in adult activities, adjust their attitude to paren-
sperm at a median age of 13.4 years (Muller et al., 1989). tal figures, and think and act more independently. In
Yet cross-cultural evidence indicates that few boys short, they begin to behave like men.
successfully father children until they are into their However – and this is where the survival advantage
third decade of life. In the United States, for example, may lie – they still look like boys. One might say that a
only 3.09% of live-born infants in 1990 were fathered by healthy, well-nourished 13.5-year-old human male, at a
men under 20 years of age. In Portugal, for years 1990, median height of 160 cm (62 inches) “pretends” to be
1994, and 1999, the percentage of fathers under 20 years more childlike than he really is. Because their adolescent
of age was always below 3% (Instituto Nacional de growth spurt occurs late in sexual development, young
Estatı́stica, 1999). In 2001, Portugal stopped presenting males can practice behaving like adults before they are
results concerning the percentage of fathers below actually perceived as adults. The sociosexual antics of
20 because there were too few of them (Instituto Nacio- young adolescent boys are often considered to be more
nal de Estatı́stica, 2001). Among the traditional Kikuyu humorous than serious. Yet, they provide the experience
of East Africa, men do not marry and become fathers to fine-tune their sexual and social roles before their
until about age 25 years, although they become sexually lives or those of their offspring depend on them. For
active after their circumcision rite at around age 18 example, competition between men for women favors
(Worthman, 1993). the older, more experienced man. Because such compe-
The explanation for the lag between sperm produc- tition may be fatal, the childlike appearance of the
tion and fatherhood is not likely to be a simple one of immature but hormonally and socially primed adoles-
sperm performance, such as not having the endurance to cent male may be life-saving as well as educational.
swim to an egg cell in the woman’s fallopian tubes. More Adolescent boys do not begin to look like men until
likely is the fact that the average boy of 13.4 years is only their spurt in muscle development, which takes place
beginning his adolescent growth spurt (Figure 22.5). at about age 17 years. Prior to this, adolescent boys are
Growth researchers have documented that in terms of fertile but still look like juveniles. This is a type of
physical appearance, physiological status, psychosocial reverse sexual selection when compared with girls.
392 Barry Bogin
Adolescent girls learn and practice adult behaviors dated at between 42 000 and 37 000 years BP. Using
when they are infertile but look like women. modern human development reference data, Thompson
Language development in adolescent boys is another and Nelson (1997) estimate that Le Moustier 1 has a
influence on social and sexual success. Indeed, vocal and dental age of 15.5 years and a stature age of 11–12 years
verbal performance is an essential aspect of sexual/ based on the length of his femur. The dental age and the
mating behavior in human beings. Adolescent speech stature age are in poor agreement, and indicate that
becomes more complex in vocabulary, including slang, Le Moustier 1 may not have followed a human pattern
more rapid in speaking rate, and assumes more rhyth- of adolescent growth (Bogin, 1999). Alternatively, Nelson
mic fluency (Locke and Bogin, 2006). Boys and men in and Thompson (2002) suggest that Neanderthals, both
many societies engage in vocal and verbal duels, use the young and adults, may have reduced limb growth
of riddles, and other complex patterns of language. due to cold adaptation (Allen’s rule). There is also the
These duels develop sequentially during adolescence. suggestion that Neanderthals of Western Europe
Those who can handle this complex vocal and verbal suffered iodine deficiency (Dobson, 1998; Bogin and
material are considered intelligent by members of the Rios, 2003). Cold adaptation and/or nutrient deficiency
social group. Anthropologists find that most oral soci- may obscure evidence for an adolescent spurt in limb-
eties, and many literate societies, promote verbal skill for length growth.
attention, power, prestige, and success (Locke and Given the uncertainties of the evidence derived
Bogin, 2006). Vocal and verbal dueling is almost always from H. antecessor and the Neanderthals, it is quite
performed in front of an audience and is often used to likely adolescence is no older than the appearance of
attract mating opportunities. archaic H. sapiens in Africa at about 125 000 years ago –
Girls and women also engage in vocal and verbal possibly even more recently at about 60 000 years ago.
contests, but less often in highly public displays. Girls With the evolution of adolescence the modern pattern
and younger women focus relatively more on social of human life history was established. With the add-
talking, including gossip, deceiving, mollifying, negotiat- ition of adolescence to human life history sociocultural
ing, and persuading (Locke and Bogin, 2006). As for boys, behaviors and forms, such as marriage and the family,
this use of language for girls does not reach adult levels of could come into being. When all of these came to exist
complexity and effectiveness until the later teenage years. is not known. From the ancient roots for the evolution
Human language, in this sense, conforms closely to of childhood to the more recent emergence of adoles-
Darwin’s examples of sexual selection for “. . . organs cence our hominin ancestors were transformed. Only
for producing vocal or instrumental music . . .” which with a life history including both childhood and adoles-
influence opportunities for mating. cence could the human species, in most essential bio-
cultural aspects, have evolved.
WHEN DID ADOLESCENCE EVOLVE?

DISCUSSION POINTS
In contrast to the relatively ancient evolution of homi-
nin childhood, an adolescent life stage may be relatively 29. How does the pattern of human brain growth
recent. Based on skeletal and dental development there during infancy and childhood help to understand
is little or no evidence of human adolescence in Homo the biological and behavioral development of
erectus or any earlier hominin (Dean et al., 2001; Antón, human beings?
2003). Moreover, the fossil evidence indicates that the 30. In what ways does human parental investment
adolescent growth stage, and the adolescent growth in offspring differ from that of other primates,
spurt, evolved only in the lineage leading directly to especially the great apes? What value does human
modern Homo sapiens. co-operative care of infants and children have for
There is a possibility that adolescence may first human reproduction and infant-child survival?
appear in Homo antesesor, a hominin from Spain that 31. Boys and girls proceed through puberty and ado-
is about 800 000 years old (Bermudez de Castro et al., lescence in different ways regarding the develop-
1999). The evidence for this is based on patterns of ment of sexual characters and adult behaviors.
tooth formation, which while not directly linked to What may be the biological and social value of the
the presence of an adolescent growth spurt is suggest- two distinct paths of development?
ive. Possible descendants of H. antecessor are the Nean- 32. Bogin proposes that human childhood is funda-
derthals. There is one fossil of a Neanderthal youth in mentally a feeding and reproductive adaptation to
which the associated dental and skeletal remains needed assist the mother’s reproductive success. Find other
to assess adolescent growth are preserved. It is called explanations for the value of human childhood and
Le Moustier 1, most likely the remains of a male, and it discuss the evidence in favor and against Bogin’s
was found in 1908 in Western France. The specimen is hypothesis.
Cobourne, M. T. and Sharpe, P. T. (2003). Tooth and jaw:

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23 Variation in Human Growth Patterns
due to Environmental Factors
Stanley J. Ulijaszek
INTRODUCTION low socioeconomic status include single parenthood,

overcrowding, low disposable income, paternal ill health,
The human growth pattern is characterized by rapid dependence on social welfare, and parental abuse of
growth in infancy, followed by an extensive period of alcohol and drugs (Schell, 1991b).
childhood, and a relatively intense adolescent spurt In both developed and developing worlds there are
(see Chapter 22 of this volume). The extended period of similar associations between stature and socioeco-
biological immaturity relative to other mammalian nomic status, height correlating positively with wealth
species is associated with high environmental sensitivity (Bogin, 1999). Weight, however, does not always relate
and growth plasticity (Johnston, 1998), illustrated by the positively with wealth, overweight and obesity being
processes of stunting and wasting in response to poor the provenance of low socioeconomic status in most
nutrition and infection (Waterlow, 1988) and of catch-up industrialized nations (Sobal, 1991), and becoming
growth during environmental improvements following increasingly so among emerging nations undergoing
episodes of environmental stress (Prader et al., 1963). the health transition (Xu et al., 2005). Growth stunting
Known environmental factors that influence in association with overweight was first identified in
growth, body size, and body composition of children Peruvian children (Trowbridge et al., 1987) and more
postnatally include nutrition (Barclay and Weaver, 2006), recently in children aged between three and nine years
infection (Bhan et al., 2001), interactions between the two in four nations viewed to be undergoing nutrition tran-
(Ruel, 2001), psychosocial stress (Powell et al., 1967), sition: Russia, Brazil, Republic of South Africa, and
food contaminants (Gong et al., 2004), pollution (Schell, China (Popkin et al., 1996).
1991a), and hypoxia (Frisancho, 1977). Most of these Early life experiences involving environmental stress,
factors are conditioned by poverty and socioeconomic intrauterine growth retardation, poor growth in early
status (Martorell et al., 1988). They are also conditioned childhood, and subsequent catch-up growth can impact
historically, culturally, and politically (Ulijaszek, 2006), on growth, body composition, and health outcomes later
interacting with each other, but also with individual in life (Henry and Ulijaszek, 1996). Catch-up growth is
genotypes in the production of growth, body size, and an acceleration of child growth-rate following either
body composition. medical or environmental intervention or environmental
Diet, nutrition, disease, hypoxia, pollution, contamin- improvement, such that body size approaches or reaches
ation, behavioral toxicants, deprivation, and psychosocial normality, as defined by appropriate growth references
stress can be clustered as proximate environmental (Prader et al., 1963). It can take place at all stages of child
agents that can influence growth (Figure 23.1). They vary growth, including adolescence (Golden, 1994). However,
in importance according to circumstance and the age and when the factors responsible for growth faltering or
stage in infancy, childhood, and adolescence. Culture, failure are ubiquitous, this process is constrained and
society, behavior, socioeconomic status, poverty, and individuals fail to reach their potential for maximal
political economy can also be clustered as structurally growth and optimal body size (Martorell et al., 1988).
powerful but distal agents in the production of Human growth and body size responds with sensi-
growth and body size outcomes, at all ages and stages tivity to environmental quality. The term “secular
of childhood and adolescence. This latter cluster is trend” is used to describe marked changes in growth
conditioned historically. In the developing world, the and development of successive generations of human
risks associated with poverty include low income, poor populations living in the same territories. Positive
food security, inadequate health infrastructure, and secular trends in increased stature and weight, and
environmental hazards. In the industrialized world, the earlier timing of the adolescent growth spurt, have
risks for impaired child growth that are associated with been documented among European, European-origin,
396
Variation in Human Growth Patterns due to Environmental Factors 397
Biological 23.1. Proximate and distal agents influencing child
Genetics
inheritance growth. Adapted from Ulijaszek (2006).
Genotype
GROWTH STATUS, GROWTH
BODY COMPOSITION INCREMENT
Diet, nutrition Disease BOX 1

Physical
environment
Hypoxia, pollution, Deprivation,
contaminants, psychosocial
toxicants stress
BOX 2
Environment
Culture Behavior Socioeconomic status,
poverty
Political economy
History
and Asian populations (Ulijaszek, 2001). Negative secu- While adolescent growth may be under stronger genetic
lar trends have been identified among populations in control than growth in childhood (Hauspie and Susanne,
Africa (Henneberg and van den Berg, 1990), Papua 1998), environment can influence both of these meas-
New Guinea (Ulijaszek, 1993), and Central and Latin ures of adolescent growth and maturation, but to a
America (Bogin, 1999). Positive secular trends have lesser extent than genetics (Bogin, 1999). This chapter
largely been attributed to improved social, political, describes important environmental influences on the
nutritional, and health conditions, while negative secu- growth of children from birth to adulthood, focusing
lar trends are often seen as outcomes of environmen- primarily on measures of height and weight, the primary
tal, social, or political deterioration (Bogin, 1999). The anthropometric measures used in child health surveil-
best example of a positive secular trend is that of lance, screening, and monitoring.
the Netherlands (Van Wieringen, 1986), where mean
stature has increased from 165cm in 1860 to 181cm
in 1990, and 184cm in 1997 (Cole, 2000). In largest INFANCY AND EARLY CHILDHOOD
part, this has been attributed to improved nutrition
(in terms of both quantity and quality) that came with Human infancy is the period when the mother provides
economic improvements across the twentieth century, all or some nourishment to her offspring by way of
as well as the control of, and decline in, infectious lactation (Bogin, 1998). Human infancy ends when the
disease morbidity (Van Wieringen, 1986). However, child is weaned from the breast, which in preindustria-
although most populations in Europe have experi- lized societies usually continues to beyond two years of
enced a positive secular trend across the twentieth age (Sellen, 2001). Exclusive breast-feeding usually
century, there is evidence that some experienced a provides adequate nutrition to support good child
negative secular trend in the late eighteenth century, growth until 6 months of age (Butte et al., 2002), and
due largely to poor harvests, high grain prices, and the dietary supplementation of the infant often begins
poor infant and child nutrition that followed (Komlos, around or before that time (Sellen, 2001). Of the various
1985; Floud et al., 1990). environmental factors influencing growth of children
The vast majority of research on environmental in developing countries, diet, nutrition, and infection
influences on human growth has focussed on birth- are particularly powerful in infancy and childhood.
weight (Wharton, 1989), infancy and infant feeding While infants are breast-fed, they are usually protected
(Frongillo, 2001), and early childhood, up to the age from the broad disease environment nutritionally,
of five years (Waterlow, 1988). Later childhood is taken immunologically (Ulijaszek, 1990), and behaviorally.
to be from five years of age until onset of puberty. In Where on-demand breast-feeding is usual, infants are
contrast, the environmental influences on preadoles- often kept close to their mother and are buffered from
cent growth have attracted relatively little attention contact with objects or foods contaminated with patho-
(Stoltzfus, 2001). Growth and body composition in gens. In developing countries, interactions between
adolescence has been researched to a greater extent than undernutrition and infection usually lead to growth
in preadolescence, but to a much smaller extent than faltering from about six months of age (Waterlow, 1988;
among in children of preschool age (Stoltzfus, 2001). Lunn 2000).
398 Stanley J. Ulijaszek
Interactions between undernutrition Inadequate dietary intake

and infection
Undernutrition-infection interactions can be initiated in
two ways (Figure 23.2). The first involves poor nutri-
tional status leading to impaired immunocompetence Anorexia Weight loss
and reduced resistance to infection, while the second Malabsorption Growth faltering
Metabolic change Immune function
involves an exposure to infectious disease which can lead Mucosal damage
to appetite loss and anorexia, malabsorption, elevated
basal metabolic rate, as well as gut mucosal damage,
and protein catabolism in order to fuel acute phase
Disease: incidence,
protein production. Delayed supplementation may lead duration, severity
to growth faltering and undernutrition, leaving the
23.2. Nutrition–infection interactions in early childhood.
infant more suspectible to infectious diseases, while
earlier dietary supplementation may provide adequate tions fall into categories (1) and (2), as do the more
nutrient intake, but concomitantly introduce the child specific diseases pneumonia, measles, malaria, and typa-
to diarrheal agents. nosomiasis (Ulijaszek, 2006). The nutritional deficiencies
Once started, the interactions between these two that inhibit immune system include energy, protein,
major environmental stressors become increasingly vitamin A, pyridoxine, iron, and zinc (Tomkins, 2002).
complex, with the nature of the disease ecology influ- However, in the absence of overt infection, deficiencies
encing the duration and severity of infection, and of zinc and iron have only a small effect on linear
adaptive immunity, its effect on subsequent disease growth, while vitamin A is unlikely to have any important
experience, and the extent, if any, of anorexia, fever, effect (Bhandari et al., 2001). Diseases known to inhibit
and malabsorption during infectious episodes, which immune system function include AIDS, measles, leprosy,
impact on nutritional status. Specific nutritional defi- and malaria. The ways in which growth faltering is asso-
ciencies can subsequently influence immune status and ciated with the interaction between undernutrition and
responsiveness, as well as adaptive immunity. In add- infection are thus manifold, and varies with specific local
ition, cultural factors and poverty can influence patterns disease and nutritional ecologies. Gut damage due to
of disease management and sickness behavior, which infection also varies across ecologies (Lunn, 2000). While
can in turn affect the incidence, severity and duration the growth outcomes of undernutrition – infection inter-
of infection, and their effects on nutritional status. actions may look similar across the developing world,
Infections that influence nutritional status and they are in fact different in specific causation.
linear growth are either acute and invasive, provoking a Growth faltering due to undernutrition and infection
systemic response (such as dysentery and pneumonia), or may continue for months or years, depending on the
chronic, affecting the host over a sustained period (includ- severity of the disease environment, and the abundance
ing gut helminth infections). Infections can diminish and quality of the nutritional environment. In most
linear growth by affecting nutritional status, by way populations, the process of growth faltering is complete
of decreased food intake, impaired nutrient absorption, by the age of two years, after which the shorter, stunted
direct nutrient losses, increased metabolic requirements, child may follow a parallel trajectory to the Western
catabolic losses of nutrients, and/or impaired transport growth references (Eveleth and Tanner, 1990). This
of nutrients to target tissues. In addition, induction period of departure from the growth references derived
of the acute phase response and host elaboration of proin- from measures of Western populations can be regarded
flammatory cytokines (Friedman et al., 2003) may con- in one sense as an accommodation to the disease and
tribute to growth faltering because they directly inhibit nutritional environment. However, this accommodation
the process of bone remodeling that is needed for long is usually associated with high rates of mortality and
bone growth (Stephensen, 1999). morbidity, reduced energy for play, and compromised
In Table 23.1, the nutrition – infection processes asso- intellectual development, and cannot therefore be
ciated with growth faltering of children are reduced to regarded as desirable.
four types of effect. These are: (1) the diseases and disease
categories that are known to affect nutritional status; (2)
Poverty
the diseases and disease categories known to be influ-
enced by nutritional status; (3) the nutritional deficien- Childhood undernutrition and infection are associated
cies that inhibit immune system function; and (4) the with poverty. Farmer (2004) has described the exten-
diseases known to inhibit immune system function. sive ways in which poverty and social inequality are
The general disease categories of diarrhea, intestinal embodied as differential risks for infection with HIV
parasitic infestation, and upper respiratory tract infec- and tuberculosis in developing countries, while Walls
TABLE 23.1. Nutrition–infection processes associated with growth faltering of children.
Diseases and disease categories known to affect nutritional status:

Diarrhea; upper respiratory tract infections; pneumonia; measles; malaria; intestinal parasites; AIDS
Diseases and disease categories known to be influenced by nutritional status:
Diarrhea; cholera; leprosy; pertussis; upper respiratory tract infections; pneumonia; measles; malaria;
intestinal parasites; trypanosomiasis
Nutritional deficiencies that inhibit immune system function:
Energy; protein; vitamin A; pyridoxine; iron; zinc
Diseases known to inhibit immune system function:
AIDS; measles; leprosy; malaria
and Shingadia (2004) identified overcrowding, pov- Mexico (Mendez-Albores et al., 2004), high levels of afla-
erty, and the HIV epidemic as contributing to the toxin often remain in the food (Plasencia, 2004).
resurgence of tuberculosis globally. Bates et al. (2004) Levels of pollutants that human populations are
identified poverty as a key factor operating at individ- exposed to vary markedly, depending partly on the degree
ual, household, and community levels in increasing of, and proximity to, industrialization (Schell, 1991b).
vulnerability to malaria, tuberculosis, and HIV infec- Generalized air pollution has been identified as an envir-
tion. Poverty also underpins the nutrition and infection onmental risk factor for poor growth of children in com-
interactions that impact on child growth. Tuberculosis, munities in Silesia and Belgium (Schell, 1991b), pollution
associated with household crowding and poverty, may from hazardous waste sites having similar effects (Paigen
not be directly associated with growth faltering, but et al., 1987). Exposure to polychlorinated biphenyls (PCB)
it is associated with nutritional status. Vitamin A can at very high doses can affect child growth, while exposure
cause growth delay when combined with infection. to lead can affect growth at moderate to low levels. The
Children born to HIV-infected women who are vitamin risk of environmental pollutant exposure to child growth
A deficient during pregnancy are more likely to experi- is increasing as developing countries industrialize. China
ence growth failure (Semba et al., 1997). Furthe- has seen pronounced increases in anthropogenic lead
rmore, HIV infection, malaria, and diarrheal disease level during the past two decades (Huh and Chen, 1999),
adversely affect growth of preschool-age children, and while in Taiwan, high serum lead levels are associated
are associated with increased prevalence of vitamin with lead exposure from drinking water sources and
A deficiency (Villamor et al., 2002). residential proximity to factories, as well as occupational
lead exposure (Chu et al., 1998).
Environmental contamination
Psychological stress
Exposure to aflatoxin contamination, particularly at the
time of weaning, has been shown to inhibit early child- The idea that psychological stress causes growth faltering
hood growth in West Africa (Gong et al., 2003). Aflatoxins in some children was first put forward by Widdowson
are mold metabolites produced by toxigenic strains of (1951), who published evidence that the presence of a
Aspergillus species, a number of which are hepatotoxic sadistic schoolteacher caused child growth in an orphan-
and immunotoxic. Primary commodities susceptible to age to falter, despite a concurrent increase in the amount
aflatoxin contamination include corn, peanuts, cotton- of food eaten. Furthermore, family conflict has been
seed, and animal-derived foods such as milk when the shown to be associated with short stature in childhood
animal is fed aflatoxin-contaminated feed. Although as well as short adult height in the British 1958 cohort
excessive aflatoxin contamination is not global, signifi- study (Montgomery et al., 1997). The dominant mechan-
cant dietary contamination has been demonstrated in ism by which short stature emerges is nutritional, by way
many parts of West Africa, Asia, and South America of appetite loss and anorexia (Skuse, 1998).
(Ulijaszek, 2006). Risks associated with aflatoxin-
contaminated foods can be reduced through the use of
Altitude
multiple processing and decontamination procedures,
including physical cleaning and separation procedures Relative to lowland populations, humans living at high
(Park, 2002), but not with simple cooking procedures altitude are more likely to be born at low birthweight and
available to poor mothers. Although aflatoxins are par- undergo postnatal growth which is slow and prolonged
tially destroyed during nixtamalization, the alkaline (Frisancho, 1993). The poor growth in infancy and early
cooking procedure employed to prepare tortillas in childhood among some high altitude populations is
associated with poverty, poor food security and exposure adiposity rebound by Rolland-Cachera et al. (1984). Early
to infectious disease, in addition to hypoxia. Ethiopians adiposity rebound has been associated with earlier age at
living at high altitude have better nutrition, growth, and menarche (Barker et al., 2001) and increased relative
socioeconomic conditions than low altitude populations, weight and obesity later in life, including during adoles-
and this is reflected in their better growth rates cence (Cameron and Demerath, 2002). Early growth
(Clegg et al., 1972), illustrating the importance of nonhy- restriction followed by catch-up growth is also associated
poxic factors influencing the growth of high altitude with the development of abdominal obesity (Dulloo,
populations. 2006), while higher growth velocity in early childhood,
prior to adiposity rebound, has been shown to be associ-
ated with greater fatness and obesity in subsequent years
GROWTH IN THE LATER CHILDHOOD, (Monteiro et al., 2003). The combination of small size at
JUVENILE AND ADOLESCENCE STAGES birth and during infancy, followed by accelerated weight
gain from age 3 to 11 years, predicts large differences in
Most of the environmental factors associated with the cumulative incidence of coronary heart disease, non-
growth in adolescence are common to growth in prea- insulin dependent diabetes, and hypertension in later life
dolescence, the most important of which are nutrition, (Barker et al., 2001). In the United States, low levels of
infection, and the interactions between the two. Add- vigorous physical activity and high levels of television
itionally, birthweight, catch-up growth, breast-feeding, viewing have been associated with fatness in children
and early adiposity rebound have impacts on growth during the adiposity rebound period (Janz et al., 2002),
and/or body composition into puberty. Growth in later and expose American children to an increased risk of
childhood and adolescence continues to show great obesity and chronic disease in adult life.
biological plasticity. Across populations, Stoltzfus (2001) In addition to undernutrition and infection, child
characterized patterns of growth that deviate greatly from neglect and abuse, exposure to industrial pollutants, food
normative patterns, as represented by growth references. contaminants, behavioral toxicants, single parenthood,
These include populations that display: (1) prepubertal overcrowding, and parental ill health are often important
catch-up growth; (2) prepubertal stunting combined with contributors to growth outcomes, according to circum-
catch-up growth in puberty; and (3) prepubertal stunting stance (Schell, 1991a). Seasonality of growth is found
with no catch-up growth in puberty. She concludes that among populations of both developed and developing
between-population variation in growth among school- countries. In the former, effects are quite subtle climatic
age children and adolescents is as great as among ones, while in the latter, they are largely due to seasonal
children in early childhood. Pattern three is the most variation in food availability and infectious disease
common across the developing world (Waterlow, 1988), exposure (Cole, 1993). If infants are breast-fed, they are
and is usually associated with poverty and low socioeco- usually shielded from most of the stresses associated with
nomic status (Martorell et al., 1988). It is also associated seasonality of infection and nutrition. However, such
with infant failure to thrive in industrialized nations, seasonal factors can become significant after weaning,
where growth-retarded children in infancy have been and persist across childhood and adolescence.
shown to remain height and weight deficit at the age The relationships between proximate and distal
of six years (Tomkins, 1994). Patterns one and two can influences on child growth (Figure 23.1) have been
occur as a result of: (1) different types of infant feeding examined at macro-level. Blakely et al. (2005) identified
and weaning behavior (Frongillo, 2001); (2) varying strong relationships between poverty and childhood
illness management practices (Tomkins 1986); (3) dietary malnutrition, access to unsafe water and sanitation,
manipulation (Steckel, 1987); and (4) changing environ- and exposure to indoor air pollution, while Frongillo
ments during childhood (Golden, 1994). The latter pat- et al. (1997) found the most important determinants of
tern has been observed to take place across secular stunting in children below the age of five years to be
trends (Proos, 1993), and during nutrition transition dietary energy availability, female literacy, and gross
(Sawaya et al., 2003). national product. In the developed world, relationships
The first two of Stoltzfus’s (2001) growth patterns, between poverty and child growth persist but perhaps
representing prepubertal catch-up growth, catch-up to a lesser extent than prior to positive secular trends
growth in puberty, and prepubertal stunting combined that took place from the late nineteenth and across the
with catch-up growth in puberty, respectively, are twentieth century (Ulijaszek, 2001).
associated with critical periods of development which
can have long-term implications for health, and body
Diet
composition in later childhood (Barker et al., 2001).
Body fatness reaches a postinfancy low level typically Both dietary quantity and quality can influence growth
between the ages of five and seven years, followed and body composition in later childhood, as can infant
by increased body fatness, a phenomenon termed feeding patterns. While there appears to be no difference
in weight and height between breast-fed and formula-fed Pollution

children by the time they reach school-age, breast-fed
Exposure of adolescents to environmental pollutants is
infants are less likely to become obese as adults (Frongillo,
different from earlier life, as the likelihood of occupa-
2001). Deficiencies of energy, protein, and zinc have
tional exposure increases, at least in the developing
been implicated in growth faltering, while diets high in
world. Perinatal exposure to polybrominated biphenyl
fat have been associated with obesity (Ulijaszek. 2006).
(PBB) has been shown to be associated with earlier age
Vegetarian and vegan diets in both developed and
at menarche (Blanck et al., 2000), while early exposure
developing countries have been shown to be deficient
to PCB is associated with delayed sexual maturation in
in micronutrients. In a study from the Netherlands,
both males and females (den Hond et al., 2002). In the
children aged 0–10 years consuming macrobiotic diets
one study in which the concurrent effects of most
with adequate protein and energy intakes and protected
common pollutants to which children might be
from bacterial contamination were shown to have
exposed was examined, Denham et al. (2005) found
growth patterns similar to those of poor children in
attainment of menarche to be sensitive to relatively
developing countries (Dagnelie et al., 1994).
low levels of lead and certain PCB congeners. Dichlor-
While broad descriptive studies of adolescent growth
odiphenyltrichloroethan (DDT) is a chemical once
are plentiful, there are few that have critically evaluated
used widely in agriculture but which is now limited
the relative importance of specific environmental factors
largely to public health use, especially in malarial
in this process. This is because of the great variation both
vector control programs in nations where equally
within- and between-populations in the maturation rate
effective and affordable alternatives are not locally
and the timing and magnitude of peak weight and height
available. The one study in the United States which
velocities. In general, adolescent growth is sensitive to
rigorously examined the possible effects of prenatal
nutritional deficit and surfeit (Eveleth and Tanner,
DDT exposure on pubertal growth and development,
1990). For many industrialized nations, there have been
found no effect (Gladen et al., 2004).
secular trends in the timing and size of the pubertal
growth spurt which have been taken as evidence for
nutritional improvement (Eveleth and Tanner, 1990).
Altitude
Furthermore, many of the socioeconomic differences
between groups in growth in adolescence have been Adolescent growth and development among populations
attributed to nutritional differences (Eveleth and Tanner, living at high altitude is often characterized by slow
1990). Despite this, there appears to be only one longitu- growth and delayed puberty, resulting in smaller
dinal study that demonstrates direct nutritional effects adult body size (Weitz and Garruto, 2004). Slower growth
on growth in adolescence (Berkey et al., 2000), among at high altitude is a consequence of hypoxia (Frisancho,
girls in Boston, in the United States. Those who con- 1993), poor economic conditions, and nutritional inad-
sumed more dietary energy and animal protein than equacy (Weitz and Garruto, 2004). A study of European
average two years before peak growth were shown to children of higher socioeconomic status migrating to
experience both earlier age at peak growth velocity, and high altitude in the Andes has shown them to be slightly
higher peak height velocity than average. The latter is shorter and lighter than their peers of same socioeco-
likely to be conditional upon the former. nomic status living at sea-level, indicating that high alti-
tude hypoxia has a small but independent impact on
growth (Stinson, 1982). There is delayed sexual matur-
ation among many, but not all, high latitude populations
Infection
relative to lower altitude populations, as well as a late and
The impacts of infection on adolescent growth are of poorly defined adolescent growth spurt, at least among
much lesser importance than nutrition. This is because Andean populations (Frisancho and Baker, 1970).
the immune system has matured and adaptive immunity
is largely in place by adolescence (Ulijaszek, 1998), and
as a consequence of this, contraction of most common CONCLUSIONS
infections of early childhood is much reduced. However,
perinatal HIV-1 infection has been shown to interfere This chapter reviews the range of environmental agents
with sexual maturation in children surviving this infec- know to influence growth in weight and stature across
tion into adolescence (Buchacz et al., 2003). Other infec- infancy, childhood, and adolescence. Diet, nutrition, dis-
tions that persist in their effects on physical growth and ease, hypoxia, pollution, contamination, behavioral toxi-
development into adolescence are tuberculosis and Heli- cants, deprivation, and psychosocial stress are clustered
cobacter pylori. Furthermore, a number of chronic disas proximate environmental agents that can influence
eases can delay onset of puberty and reduce the size of growth, which vary in importance according to circum-
the pubertal growth spurt (Simon, 2002). stance and the age and stage in infancy, childhood, and
adolescence. Culture, society, behavior, socioeconomic Bhandari, N., Bahl, R. and Taneja, S. (2001). Effect of micro-
status, social status, poverty, and political economy are nutrient supplementation on linear growth of children.
clustered as structurally powerful but distal agents in the British Journal of Nutrition, 85(suppl. 2), S131–S137.
production of growth and body size outcomes, at all ages Blakely, T., Hales, S., Kieft, C., et al. (2005). The global
and stages of childhood and adolescence. Early life distribution of risk factors by poverty level. Bulletin of the
World Health Organization, 83, 118–126.
experiences involving environmental stress, intrauterine
Blanck, H. M., Marcus, M., Tolbert, P. E., et al. (2000). Age
growth retardation, poor growth in early childhood, and
at menarche and Tanner stage in girls exposed in utero and
subsequent catch-up growth can impact on growth, body
postnatally to polybrominated biphenyl. Epidemiology,
composition, and health outcomes later in life. 11, 641–647.
The extent to which human growth and body size Bogin, B. (1998). Patterns of human growth. In Encyclopedia
responds with sensitivity to environmental quality is of Human Growth and Development, S. J. Ulijaszek,
demonstrated in the secular trends in growth and body F. E. Johnston and M. A. Preece (eds). Cambridge:
size that have taken place across successive gener- Cambridge University Press, pp. 91–95.
ations of human populations living in the same terri- Bogin, B. (1999). Patterns of Human Growth, 2nd edn.
tories. These have been mostly positive, resulting from Cambridge: Cambridge University Press.
environmental improvements, but negative trends Buchacz, K., Rogol, A. D., Lindsey, J. C., et al. (2003). Delayed
have also been demonstrated. Developmental plasticity onset of pubertal development in children and adolescents
is an adaptive property of humans that allows them with perinatally acquired HIV infection. Journal of Acquired
to survive and thrive in very varied environmental Immune Deficiency Syndromes, 33, 56–65.
Butte, N. F., Lopez-Alarcon, M. G. and Garza, C. (2002). Nutrient
circumstances.
Adequacy of Exclusive Breastfeeding for the Term Infant
during the First Six Months of Life. Geneva: World Health
Organization.
DISCUSSION POINTS
Cameron, N. and Demerath, E. W. (2002). Critical periods in
human growth and their relationship to diseases of aging.
1. In what ways does plasticity in human develop- Yearbook of Physical Anthropology, 45, 159–184.
ment manifest itself, and what are its longer-term Chu, N. F., Liou, S. H., Wu, T. N., et al. (1998). Risk factors
consequences? for high blood lead levels among the general population in
2. What is important about the secular trend in Taiwan. European Journal of Epidemiology, 14, 775–781.
growth and body size? Clegg, E. J., Pawson, I. G., Ashton, E. H., et al. (1972). The
3. How does growth and development in early child- growth of children at different altitudes in Ethiopia. Philo-
hood differ from that in later childhood? sophical Transactions of the Royal Society of London. Series
4. How do environmental factors that influence child B, 264, 403–437.
growth cluster together? Cole, T. J. (1993). Seasonal effects on physical growth
5. In what ways do nutrition and infection influence and development. In Seasonality and Human Ecology,
patterns of growth and development from birth S. J. Ulijaszek and S. S. Strickland (eds). Cambridge:
Cambridge University Press, 89–106.
and into adolescence?
Cole, T. J. (2000). Secular trends in growth. Proceedings of
the Nutrition Society, 59, 317–324.
Dagnelie, P. C., van Dusseldorp, M., van Staveren, W. A.,
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24 Evolutionary Biology of Hormonal
Responses to Social Challenges in the
Human Child
Mark V. Flinn
The human child is remarkably tuned-in to his or United States indicate that chronic stress is similarly
her social environment. He or she is an informational associated with a long-term three-fold increase in
sponge, absorbing bits of knowledge from others at adverse health conditions (Cohen et al., 1993, 2007).
a phenomenal pace, equipped with life’s most sophisti- Exposure to stressful events early in development,
cated and creative communication system (human moreover, appears to have lifelong effects (Heim et al.,
language). This sensitivity to social interactions is inter- 2002; Fox et al., 2007; Kolassa and Elbert, 2007; Meaney
woven with the ontogeny of flexible cognitive skills – et al., 2007; Champagne, 2008; Seckl, 2008). Stress
including empathy, self awareness, social-scenario endocrinology is suspected to have an important role
building, and theory of mind (ToM) – that are the foun- in the links between social environment and health.
dation of human relationships. In this chapter Chronic release of stress hormones such as cortisol in
I examine the neuroendocrine systems that facilitate response to psychosocial challenges is posited to have
the development of these distinctively human sociocog- incidental deleterious effects on immune and metabolic
nitive adaptations. regulatory functions (Ader et al., 2001; Sapolsky, 2005).
Neuroendocrine systems may be viewed as com- Release of androgens such as testosterone, dehydroe-
plex sets of mechanisms designed by natural selection piandrosterone (DHEA), and dehydroepiandrosterone
to communicate information among cells and tissues. sulfate (DHEAS) are also influenced by social condi-
Steroid and peptide hormones, associated neurotrans- tions (see Chapter 16 of this volume), and can affect
mitters, and other chemical messengers guide behav- immunocompetence (Muehlenbein and Bribiescas,
iors of mammals in many important ways (Ellison, 2005; Muehlenbein, 2008).
2001; Lee et al., 2009; Panksepp, 2009). Analysis of This importance of the social environment for
patterns of hormone levels in naturalistic contexts a child’s physical and mental health presents an evolu-
can provide important insights into the evolutionary tionary puzzle. Why, given the apparent high cost
functions of the neuroendocrine mechanisms that to human health of psychosocial stress, would natural
guide human behaviors. Here I focus on the apparent selection have favored links between the psycho-
evolutionary paradox of neuroendocrine response to logical mechanisms that assess social challenges,
psychosocial stressors. and the neuroendocrine mechanisms that regulate
Acute and chronic stressful experiences are associ- stress and reproductive physiology and downstream
ated with a variety of negative health outcomes in immune functions? I approach this question from
humans, including susceptibility to upper respiratory the integrative evolutionary paradigm of Niko
infections (Cohen et al., 2003), anxiety and depression Tinbergen (1963), who emphasized the importance of
(Heim and Nemeroff, 2001), and coronary heart dis- linking proximate physiological explanations with
ease (McEwen, 1998). The effects of psychosocial ontogeny (development), phylogeny (ancestry), and
stress can be substantial: in the rural community of adaptive function (natural selection). My basic argu-
Bwa Mawego, Dominica, where I have studied child ment is that hormonal stress response to psychosocial
health for the past 22 years, overall morbidity among challenges facilitates the neural remodeling and poten-
children for the 3–6 days following an acute stress tiation that is necessary to adapt to the dynamic infor-
event is more than double the normal rate (Flinn and mational arms race of the human sociocultural
England, 2003). Studies of populations within the environment.
405
406 Mark V. Flinn
WHY IS THE HUMAN CHILD SO SENSITIVE the paradox of hormonal response to social challenge,
TO THE SOCIAL ENVIRONMENT? hypothesizing that glucocorticoids and androgens help
facilitate neural remodeling and long-term potentia-
The human child is a social creature, motivated by and tion necessary for dynamic social cognition.
highly sensitive to interpersonal relationships (Gopnik
et al., 1999). The life history stage of human childhood
Paternal care in multimale groups
enables the development of necessary social skills
(Alexander, 1987; Joffe, 1997; Bogin, 1999; Geary and Mammals that live in groups with multiple males –
Bjorklund, 2000; Flinn, 2004), including emotional such as chimpanzees (Pan troglodytes) – usually have
regulation. Learning, practice, and experience are little or no paternal care, because the nonexclusivity of
imperative for social success. The information process- mating relationships obscures paternity (Alexander,
ing capacity used for human social interactions is con- 1974; Clutton-Brock, 1991). Chimpanzee males appear
siderable, and perhaps significantly greater than that to lack reliable cues for identifying their offspring.
involved with foraging skills (Roth and Dicke, 2005). In contrast, it is common for human fathers to provide
The child needs to master complex dynamic protection, information, food, and social status for
tasks such as learning the personalities, social biases, their children. Paternal care in humans appears to
relationships, and so forth of peers and adults in the be facilitated by relatively stable pair bonds, which
local community, and developing appropriate cogni- not only involves co-operation between mates that
tive and emotional responses to these challenges often endures over the life span, but which requires
(Bugental, 2000). The learning environments that an unusual type of co-operation among coresiding
facilitate and channel these astonishing aspects of males – respect for each other’s mating relationships.
human mental phenotypic plasticity appear to take on The relatively exclusive mating relationships that
a special importance. Much of the data required for the are characteristic of humans generate natural factions
social behavior necessary to be successful as a human within the group. Mating relationships also can create
cannot be “preprogrammed” into specific, detailed, alliances in human groups, linking two families or
fixed responses. Social cleverness in a fast-paced, clans together. By way of comparison, in chimpanzee
cumulative cultural environment must contend with communities it is difficult for even the most dominant
dynamic, constantly shifting strategies of friends and male to monopolize an estrous female; most of the
enemies, and hence needs information from experien- males in a community mate with most of the females
tial social learning (Flinn, 1997, 2006a). The links (Goodall, 1986). Although dominant males sire a
among psychosocial stimuli, emotions, and physio- higher proportion, chimpanzee males in effect “share”
logical stress response may guide both the acute and a common interest in the community’s females and
long-term neurological plasticity necessary for their offspring. Human groups, in contrast, are com-
adapting to the dynamic aspects of human sociality. posed of family units, each with distinct reproductive
interests. Human males do not typically share mating
access to all the group’s females; consequently, there
HUMAN SOCIALITY: KEY EVOLUTIONARY are usually reliable cues identifying which children are
PUZZLES their genetic offspring, and which are those of other
males (for variations see Flinn, 1981; Beckerman and
Humans are characterized by a distinctive set of traits, Valentine, 2002). Because humans live in multimale
including: (1) large brains; (2) long periods of juvenile groups, yet typically maintain fairly stable mating rela-
dependence; (3) extensive biparental care including tionships, the potential for fission along family lines is
large transfers of information; (4) multigenerational high. Still, human groups overcome this inherent con-
bilateral kin networks; (5) habitual bipedal locomo- flict between family units to form large, stable coali-
tion; (6) use of the upper limbs for tool use including tions (Chapais, 2008).
projectile weapons; (7) concealed or “cryptic” ovula- This unusual tolerance among coresidential males
tion; (8) menopause; (9) culture including language; and females stands in contrast to the norm of polyg-
and (10) lethal competition among kin-based coali- amous mate competition in nonhuman primates.
tions. A few other species exhibit several of these traits; Selection pressures favoring such tolerance are uncer-
only humans, however, are characterized by the entire tain, but likely involve the importance of both male
combination (Alexander, 2005). This suite of traits pre- parental investment (Alexander, 1990b; Geary and
sents several questions or puzzles that are key to Bjorklund, 2000) and male coalitions for intraspecific
understanding human evolutionary biology. Here conflict (Alexander, 1989, 2006; Wrangham, 1999;
I first briefly describe these puzzles, and suggest a Geary and Flinn, 2001; Bernhard et al., 2006). The
common resolution based on the importance of social hormonal mechanisms that enable these unusual
competition during human evolution. I then return to aspects of human male relationships are uncertain.
Evolutionary Biology of Hormonal Responses to Social Challenges in the Human Child 407
Analysis of patterns of levels of candidate hormones – and enhanced integration of the cerebellum also
such as vasopressin, testosterone, DHEA/S and appear significant (Allman, 1999; Amodio and
cortisol – in natural social conditions may provide Frith, 2006). In comparison with most other parts of
useful clues as to the evolved functions of male the human genome, selection on genes involved with
coalitions and pair bonding among humans. brain development was especially intense (Gilbert
et al., 2005).
The human brain has high metabolic costs: about
An extended period of juvenile dependence
50% of an infant’s, and 20% of an adult’s, energetic
and child development
resources are used to support this neurological activity
The human baby is unusually altricial (helpless). (Aiello and Wheeler, 1995). Although the increase in
Infants must be carried, fed, and protected for a energetic resources allocated to the brain was accom-
long period in comparison with other primates. panied by a corresponding decrease in digestive tissue,
Human childhood and adolescence are also lengthy this does not explain what the selective pressures
(Smith, 1994; Bogin, 1999; Leigh, 2004). This extension were for enhanced information processing, or why
of the juvenile period that delays reproduction the resources were not reallocated to direct reproduct-
for much longer than the other hominoids appears ive function. The obstetric difficulties associated with
costly in evolutionary terms. Parental and other birthing a large-headed infant generate additional
kin investment continues for an unusually long time, problems (Rosenberg and Trevathan, 2002). The select-
often well into adulthood and perhaps even after ive advantages of increased intelligence must have
the death of the parents (Alexander, 1987; Coe, 2003; been high to overcome these costs.
Hrdy, 2009). The human brain, in short, is a big evolutionary
The selective pressures responsible for this unique puzzle. It is developmentally and metabolically expen-
suite of life history characteristics appear central to sive, evolved rapidly, enables uniquely human cogni-
understanding human evolution (Alexander, tive abilities such as language, empathy, foresight,
1990a, 1990b; Kaplan et al., 2000; Bjorklund and consciousness, and ToM, and generates unusual
Pellegrini, 2002; Rosenberg, 2004). The normal delay levels of novelty. Advantages of a larger brain may
of reproduction until at least 15 years of age involves include enhanced information processing capacities
prolonged exposure to extrinsic causes of mortality to contend with ecological pressures that involve sexu-
and longer generation intervals. What advantages of ally dimorphic activities such as hunting and complex
an extended childhood could have outweighed the foraging (Kaplan and Robson, 2002). There is little
heavy costs of reduced fecundity and late reproduction evidence, however, of sufficient domain-specific
(Williams, 1966; Stearns, 1990) for our hominin enlargement of those parts of the brain associated
ancestors? with selective pressures from the physical environ-
ment (Geary and Huffman, 2002; Adolphs, 2003).
Indeed, human cognition has little to distinguish itself
Intelligence, information, and social power
in the way of specialized ecological talents. A large
The human brain is an astonishing organ. Its cortex brain may have been sexually selected because it was
comprises about 30 billion neurons of 200 different an attractive trait for mate choice (Miller, 2000; Gavri-
types, each of which are interlinked by about a thou- lets and Vose, 2006). However, there is little sexual
sand synapses, resulting in a million billion connec- dimorphism in encephalization quotient or intelli-
tions working at rates of up to ten billion interactions gence psychometrics (Jensen, 1998), nor is there a
per second (Williams and Herrup, 1988; Koch, 1999; clear reason why brains would have been a target for
Edelman, 2006). Quantifying the transduction of sexual selection driven by mate choice uniquely
these biophysical actions into specific cognitive among hominins.
activities – e.g., thoughts and emotions – is difficult, One area in which humans are truly extraordinary
but it is likely that humans have more information is sociality. Humans are able to mentally represent
processing capacity than any other species (Roth and the feelings and thoughts of others. Humans have
Dicke, 2005). unusually well-developed mechanisms for ToM (Leslie
The human brain evolved at a rapid pace: hominin et al., 2004; Amodio and Frith, 2006), and associated
cranial capacity tripled (from an average of about specific pathologies in this domain (Baron-Cohen,
450 to 1350 cc) in less than 2 million years 1995; Gilbert, 2001). We have exceptional linguistic
(Lee and Wolpoff, 2003) – roughly 100 000 neurons abilities for transferring information from one brain
and supportive cells per generation. Structural changes to another (Pinker, 1994), enabling complex social
such as increased convolutions, thickly myelinated learning. Social and linguistic competencies are
cortical neurons, lateral asymmetries, increased roughly equivalent in both males and females,
von Economo neurons, expansion of the neo-cortex, although human mothers appear to have especially
408 Mark V. Flinn
important roles in the development of their offspring’s THE SOCIAL ENVIRONMENT AS A KEY
sociocognitive development (Simons et al., 2001; SELECTIVE PRESSURE
Deater-Deckard et al., 2004).
Information processing is a core human adaptation
Human coalitionary dynamics appear to have
become increasingly based on information and social Children are especially tuned to their social worlds
skills. Intense intergroup competition created pressure and the information that it provides. The social world is
for within-group social cohesion (Alexander, 1990a; a rich source of useful information for cognitive develop-
Flinn et al., 2005a) that required not only fighting ment. The human brain appears designed by natural
abilities, but complex social strategies. selection to take advantage of this bonanza of data
(Tooby and Cosmides, 1992; Bjorklund and Pellegrini,
2002; Belsky, 2005). “Culture” may be viewed as a highly
Kin networks and multiple caretakers
dynamic information pool that coevolved with the exten-
All human societies recognize kinship as a key organi- sive information processing abilities associated with our
zational principle (Brown, 1991). All languages have flexible communicative and sociocognitive competen-
kinship terminologies and concomitant expectations cies (Alexander, 1979). With the increasing importance
of nepotism (Murdock, 1949; Fortes, 1969). Human and power of information in hominin social interaction,
kinship systems appear unique in the consistency of culture and tradition may have become an arena of social
both bilateral (maternal and paternal) and multige- co-operation and competition (Coe, 2003; Flinn, 2004,
nerational structure, with a general trend for coresi- 2006a; Baumeister, 2005).
dence of male kin. These aspects of human kinship The key issue is novelty. One of the most difficult
link families into broader co-operative systems, and challenges to understanding human cognitive evolu-
provide additional opportunities for alloparental care tion, and its handmaiden culture, is the unique
during the long social childhood. Human grandparents informational arms race that underlies human behav-
stand out as unusually important in this regard (Hrdy, ior. The reaction norms posited by evolutionary psych-
2005; Flinn and Leone, 2006, 2009). ology to guide evoked culture within specific domains
Grandparents and grand-offspring share 25% of may be necessary but insufficient (Chiappe and
their genes identical by descent, a significant oppor- MacDonald, 2005). The mind does not appear limited
tunity for kin selection. Few species, however, live in to a predetermined Pleistocene set of options – such
groups with multiple overlapping generations of kin. as choosing mate A if in environment X, but choose
Fewer still have significant social relationships among mate B if in environment Y – analogous to examples
individuals two or more generations apart. Humans of simple phenotypic plasticity (MacDonald and
appear rather exceptional in this regard. Grandparent- Hershberger, 2005).
ing is cross-culturally ubiquitous and pervasive Keeping up in the hominin social chess game
(Murdock, 1967; Sear et al., 2000). Our life histories requires imitation. Getting ahead favors creativity to
allow for significant generational overlaps, including produce new solutions to beat the current winning
an apparent extended postreproductive stage facili- strategies. Random changes, however, are risky and
tated by the unique human physiological adaptation ineffective. Hence the importance of cognitive abilities
of menopause (Alexander, 1974, 1987; Hawkes, 2003). to hone choices among imagined innovations in ever
The significance of emotional bonding between more complex social scenarios. The theater of the mind
grandparents and grandchildren is beyond doubt. The that allows humans to “understand other persons as
evolved functions are uncertain, but likely involve intentional agents” (Tomasello, 1999, p. 526) provides
the exceptional importance of long-term extensive the basis for the evaluation and refinement of creative
and intensive investment for the human child. solutions to the never-ending novelty of the social
The emotional and cognitive processes that guide arms race. This process of filtering the riot of novel
grand-relationships must have evolved because they information generated by the creative mind favored
enhanced survival and eventual reproductive success the cognitive mechanisms for recursive pattern recog-
of grandchildren. In addition to the physical basics of nition in the “open” domains of both language (Pinker,
food, protection, and hygienic care, development of the 1994, 1997; Nowak et al., 2001) and social dynamics
human child is strongly influenced by the dynamics of (Geary, 2005; Flinn, 1997, 2006a). Cultural “traditions”
the social environment (Konner, 1991; Hetherington, passed down through the generations also help con-
2003a, 2003b; Dunn, 2004). Grandparents may have strain the creative mind (Coe, 2003; Flinn and Coe,
knowledge and experience that are important and 2007). The evolutionary basis for these psychological
useful for helping grandchildren and other relatives mechanisms underlying the importance of social
succeed in social competition (Coe, 2003). Humans learning and culture appears rooted in a process of
are unusual in the role of kin in alloparental care and “runaway social selection” (Alexander, 2005; Flinn
group coalitions (Hrdy, 2009). and Alexander, 2007).
Runaway social selection selective pressure via social competition involving

coalitions (Alexander, 1989; Geary and Flinn, 2002),
Darwin (1871) recognized that there could be import-
and dominance of their ecologies involving niche con-
ant differences between: (1) selection occurring as a
struction (Laland et al., 2000). The primary functions
consequence of interaction with ecological factors
of the most extraordinary and distinctive human
such as predators, climate, and food; and (2) selection
mental abilities – language, imagination, self-awareness,
occurring as a consequence of interactions among con-
ToM, foresight, and consciousness – involve the nego-
specifics, i.e., members of the same species competing
tiation of social relationships (Siegal and Varley, 2002;
with each other over resources such as nest sites,
Tulving, 2002; Flinn et al., 2005a). The multiple-party
food, and mates. The former is termed “natural selec-
reciprocity and shifting nested subcoalitions charac-
tion” and the latter “social selection” of which sexual
teristic of human sociality generate especially difficult
selection may be considered a special subtype (West-
information processing demands for these cognitive
Eberhard, 1983). The pace and directions of evolution-
facilities that underlie social competency. Hominin
ary changes in behavior and morphology produced
social competition involved increasing amounts of
by these two types of selection – natural and social –
novel information and creative strategies. Culture
can be significantly different (Fisher, 1930; West-
emerged as an intensive selective pressure on the
Eberhard, 2003).
evolving brain.
Selection that occurs as a consequence of inter-
actions between species can be intense and unending –
for example with parasite-host red queen evolution Evolution of the cultural brain
(Hamilton et al., 1990) and other biotic arms races.
Intraspecific social competition may generate selective As noted above, the human brain is a big evolutionary
pressures that cause even more rapid and dramatic paradox. It has high metabolic costs, takes a long time
evolutionary changes. Relative to natural selection, to develop, evolved rapidly, enables behavior to
social selection has the following characteristics (West- change quickly, has unique linguistic and social apti-
Eberhard, 1983): (1) The intensity of social selection tudes, and generates unusual levels of informational
(and consequent genetic changes) can be very high novelty. Its primary functions include dealing with
because competition among conspecifics can have other human brains (Adolphs, 2003; Alexander, 2005;
especially strong effects on differential reproduction. Amodio and Frith, 2006). The currency is not foot-
(2) Because the salient selective pressures involve com- speed or antibody production, but the generation
petition among members of the same species, the normal and processing of data in the social worlds of the
ecological constraints are often relaxed for social selec- human brains’ own collective and historical informa-
tion. Hence traits can evolve in seemingly extreme and tion pools. Some of the standout features of the
bizarre directions before counter-balancing natural human brain that distinguish us from our primate
selection slows the process. (3) Because social competi- relatives are asymmetrically localized in the prefrontal
tion involves relative superiority among conspecifics, cortex, including especially the dorsolateral prefrontal
the bar can be constantly raised in a consistent direction cortex and frontal pole (Ghazanfar and Santos, 2004;
generation after generation in an unending arms race. for review see Geary, 2005). These areas appear to be
(4) Because social competition can involve multiple iter- involved with “social scenario building” or the ability
ations of linked strategy and counter-strategy among to “see ourselves as others see us so that we may
interacting individuals, the process of social selection cause competitive others to see us as we wish them to”
can become autocatalytic, its pace and directions partly (Alexander, 1990b, p. 7), and are linked to specific social
determined from within, generating what might be abilities such as understanding sarcasm (Shamay-
termed “secondary red queens.” For example, reoccur- Tsoory et al., 2005) and morality (Moll et al., 2005).
rence of social competition over lifetimes and gener- An extended childhood seems to enable the develop-
ations can favor flexible phenotypic responses such as ment of these necessary social skills (Joffe, 1997).
social learning that enable constantly changing strat-
egies. Phenotypic flexibility of learned behavior to con-
tend with a dynamic target may benefit from enhanced
Evolution of the human family as a nest for the
information processing capacities, especially in regard
child’s social mind
to foresight and scenario-building. To summarize, the human family is the nexus for the
Human evolution appears characterized by these suite of extraordinary and unique human traits. Humans
circumstances generating a process of runaway social are the only species to live in large multimale groups
selection (Alexander, 2005; Flinn and Alexander, with complex coalitions and extensive paternal and allo-
2007). Humans, more so than any other species, parental care, and the altricial infant is indicative of a
appear to have become their own most potent protective environment provided by intense parenting
410 Mark V. Flinn
and alloparental care in the context of kin groups Humans exhibit a unique “nested family” social struc-
(Chisholm, 1999). The human baby does not need to ture, involving complex reciprocity among males and
be physically precocial, instead the brain continues females to restrict direct competition for mates among
rapid growth, and the corresponding cognitive compe- group members.
tencies largely direct attention toward the social environ- It is difficult to imagine how this system of pair
ment. Plastic neural systems adapt to the nuances of the bonds and male coalitions could be maintained in the
local community, such as its language (Alexander, absence of another unusual human trait: concealed or
1990a; Geary and Bjorklund, 2000; Bjorklund and ‘cryptic’ ovulation (Alexander and Noonan, 1979).
Pellegrini, 2002; Fisher, 2005). In contrast to the slow Human groups tend to be male philopatric (males
development of ecological skills of movement, fighting, tending to remain in their natal groups), resulting in
and feeding, the human infant rapidly acquires skill extensive male kin alliances, useful for competing
with the complex communication system of human against other groups of male kin (Wrangham and
language (Pinker, 1994; Sakai, 2005). The extraordinary Peterson, 1996; LeBlanc, 2003). However, unlike chim-
information-transfer abilities enabled by linguistic com- panzees, human groups and communities are often
petency provide a conduit to the knowledge available composed of several bilateral kin factions, interwoven
in other human minds. This emergent capability for by pair bond relationships among them. Human
intensive and extensive communication potentiates the females also have complex alliances, but usually are
social dynamics characteristic of human groups not involved directly in the overt physical aggression
(Deacon, 1997; Dunbar, 1998) and provides a new mech- characteristic of intergroup relations (Campbell, 2002;
anism for social learning and culture. Geary and Flinn, 2002). Parents and other kin may be
An extended childhood appears useful for acquir- especially important for the child’s mental develop-
ing the knowledge and practice to hone social ment of social and cultural maps because they can be
skills and to build coalitional relationships necessary relied upon as landmarks who provide relatively honest
for successful negotiation of the increasingly intense information. From this perspective, the evolutionary
social competition of adolescence and adulthood. significance of the human family in regard to child
Ecologically related play and activities (e.g., explor- development is viewed more as a nest from which
ation of the physical environment) are also important social skills may be acquired than just as an economic
(e.g., Geary et al., 2003), but appear similar to that of unit centered on the sexual division of labor (Flinn
other primates. The unusual scheduling of human et al., 2005b).
reproductive maturity, including an “adrenarche” To summarize my argument to this point, human
(patterned increases in adrenal activities preceding childhood is viewed as a life history stage that
puberty) and a delay in direct mate competition among appears necessary and useful for acquiring the infor-
males appears to extend the period of practicing social mation and practice to build and refine the mental
roles and extends social ontogeny (Campbell, 2006; algorithms critical for negotiating the social coalitions
Del Giudice 2009; Flinn et al., 2009). that are key to success in our species. Mastering
The advantages of intensive parenting, including the social environment presents special challenges
paternal protection and other care, require a most for the human child. Social competence is difficult
unusual pattern of mating relationships: moderately because the target is constantly changing and
exclusive pair bonding in multiple-male groups. similarly equipped with ToM and other cognitive abil-
No other primate (or mammal) that lives in large, ities. The family environment, including care from
co-operative multiple-reproductive-male groups has fathers and grandparents, is a primary source and
extensive male parental care, although some protec- mediator of the ontogeny of social competencies.
tion by males is evident in baboons (Buchan et al., Human biology has been profoundly affected by our
2003). Competition for females in multiple-male evolutionary history as unusually social creatures,
groups usually results in low confidence of paternity including, perhaps, a special reliance upon smart
(e.g., chimpanzees). Males forming exclusive mothers, co-operative fathers, and helpful grandpar-
“pair bonds” in multiple-male groups would provide ents. Indeed, the mind of the human child may
cues of nonpaternity to other males, and hence have design features that enable its development as a
place their offspring in great danger of infanticide group project, guided by the multitudinous informa-
(Hrdy, 1999). Paternal care is most likely to be favored tional contributions of its ancestors and codescen-
by natural selection in conditions where males can dants (Coe, 2003; Hrdy, 2009). Studies of the
identify their offspring with sufficient probability to patterns of hormonal responses to these complex
offset the costs of investment, although reciprocity components of human sociality may provide import-
with mates is also likely to be involved (Smuts and ant clues about the selective pressures that guided
Smuts, 1993; Geary and Flinn, 2001; Chapais, 2008). human evolution.
NEUROENDOCRINE RESPONSE TO THE SOCIAL unique designs, such as romantic love (Fisher et al.,
ENVIRONMENT 2002), that involve shared endogenous messengers
from our phylogenetic heritage.
The constellation of behaviors associated with the Attachments or bonding are central in the lives of
human family and the dynamics of social competition the social mammals. Basic to survival and reproduc-
described in previous sections are enabled by complex tion, these interdependent relationships are the fabric
regulatory systems. In this section, I first briefly review of the social networks that permit individuals to main-
the potential mechanisms for human pair bonding, tain co-operative relationships over time. Although
maternal and paternal attachment to offspring, kin attachments can provide security and relief from
attachment, and male coalitions. Much of the research stress, close relationships also exert pressures on indi-
on the basic mechanisms has been done with nonhu- viduals to which they continuously respond. It should
man models and is not easily applied directly to some not be surprising, therefore, that the neuroendocrine
aspects of human psychology. I then turn to a more mechanisms underlying attachment and stress are
detailed analysis of how the neuroendocrine stress intimately related to one another. And although at the
response system functions to enable acquisition of present time a good deal more is known about the
social competencies during childhood in the context stress response systems than the affiliative systems,
of the human family environment. some of the pieces of the puzzle are beginning to fall
The chemical messenger systems that orchestrate into place (Panksepp, 2004).
the ontogeny and regulation of sexual differentiation, The mother–offspring relationship is at the core of
metabolism, neurogenesis, immune function, growth, mammalian life, and it appears that some of the bio-
and other complex somatic processes, tend to be evo- chemistry at play in the regulation of this intimate
lutionarily conservative among primates and more bond was also selected to serve in primary mechanisms
generally among mammals. Hence rodent and nonhu- regulating bonds between mates, paternal care, the
man primate models provide important comparative family group, and even larger social networks
information about the functions of specific human (Hrdy, 1999; Fisher et al., 2002). Although a number
neuroendocrine systems, for which we often have little of hormones and neurotransmitters are involved in
direct empirical research. It is the particular balance of attachment and other components of relationships,
human mechanisms and abilities that is unique and the two peptide hormones, oxytocin (OT) and arginine-
reflects the history of selection for complex social vasopressin (AVP), appear to be primary (Carter, 2002;
interactions that shaped the human lineage. Young and Insel, 2002; Curtis and Wang, 2003; Lim
et al., 2004; Heinrichs and Domes, 2008; Lee et al.,
2009), with dopamine, cortisol, and other hormones
and neurotransmitters having mediating effects.
The chemistry of affection
The hypothalamus is the major brain site where OT
Some of the most precious of all our human feelings and AVP (closely related chains of nine amino acids)
are stimulated by close social relationships: a mother are produced. From there they are released into the
holding her newborn infant for the first time, brothers central nervous system (CNS) as well as transported
reunited after a long absence, or lovers entangled in to the pituitary where they are stored until secreted
each other’s arms. Natural selection has designed into the bloodstream. Oxytocin and AVP act on a wide
our neurobiological mechanisms, in concert with our range of neurological systems, and their influence
endocrine systems, to generate potent sensations in varies among mammalian species and stage of devel-
our interactions with these most evolutionarily signifi- opment. The neurological effects of OT and AVP
cant individuals. We share with our primate relatives appear to be key mechanisms (e.g., Bartels and Zeki,
the same basic hormones and neurotransmitters that 2004) involved in the evolution of human family behav-
underlie these mental gifts. But our unique evolution- iors. The effects of OT and AVP in humans are likely to
ary history has modified us to respond to different be especially context dependent, because of the vari-
circumstances and situations; we are rewarded and able and complex nature of family relationships.
punished for somewhat different stimuli than our
phylogenetic cousins. Chimpanzees and humans share
the delight – the sensational reward – when biting into
Parental care
a ripe, juicy mango. But the endocrine, neurological,
and associated emotional responses of a human father Along with OT and AVP, prolactin, estrogen, and pro-
to the birth of his child (e.g., Storey et al., 2000) are gesterone are involved in parental care among
likely to be quite different from those of a chimpanzee mammals (Insel and Young, 2001). The roles of these
male. Happiness for a human (Buss, 2000) has many hormones vary across species and between males and
412 Mark V. Flinn
females. The effects of these hormones are influenced Fisher et al., 2006). These studies also demonstrate
by experience and context. Among rats, for example, that the neural regions involved in attachment acti-
estrogen and progesterone appear to prime the brain vated in humans are similar to those activated in non-
during pregnancy for parental behavior. Estrogen has human animals. Among humans, however, neural
been found to activate the expression of genes that regions associated with social judgment and assess-
increase the receptor density for OT and prolactin, ment of the intentions and emotions of others
thus increasing their postnatal influence (Young and exhibited some deactivation during attachment activ-
Insel, 2002). ities, suggesting possible links between psychological
Oxytocin is most well known for its role in regulat- mechanisms for attachment and management of social
ing birth and lactation, but along with AVP, it has also relationships. Falling in love with a mate and affective
been found to play a central role in maternal care and bonds with offspring may involve temporary deactiva-
attachment (Fleming et al., 1999). Just prior to birth, tion of psychological mechanisms for maintaining an
an increase in OT occurs, which is seen as priming individual’s social “guard” in the complex reciprocity
maternal care. An injection of OT to virgin rats has of human social networks. Dopamine levels are likely
been found to induce maternal care, while an OT to be important for both types of relationship but may
antagonist administered to pregnant rats interferes involve some distinct neural sites. It will be interesting
with the development of maternal care (Carter, 2002). to see what fMRI studies of attachment in human
The new rat mother requires hormonal activation males indicate because that is where the
to initially stimulate maternal behavior. Once she has most substantial differences from other mammals
begun to care for her pups, however, hormones are not would be expected. Similarly, fMRI studies of attach-
required for maternal behavior to continue. Olfactory ment to mothers, fathers, and alloparental-care pro-
and somatosensory stimulation from interactions viders in human children may provide important
between pups and mother are, however, required for insights into the other side of parent–offspring
the parental care to continue (Fleming et al., 1999). bonding.
The stimulation from suckling raises OT levels in
rodents and breast-feeding women, which then results
Paternal care
in not only milk letdown but also a decrease in limbic
hypothalamic-anterior pituitary-adrenal cortex system Paternal care is not common among mammals. For
(HPA) activity and a shift in the autonomic nervous evolutionary reasons noted earlier, it is found among
system (ANS) from a sympathetic tone to a parasympa- some rodent and primate species, including humans.
thetic tone. This results in a calmness seen as condu- The extent and types of paternal care vary among
cive to remaining in contact with the infant. It also species. The hormonal influence in parental care
results in a shift from external-directed energy toward among males appears to differ somewhat from that
the internal activity of nutrient storage and growth found among females. Vasopressin (AVP) appears to
(Uvnas-Moberg, 1998). function as the male addition to OT (Young and
Experience also affects the neuroendocrine Insel, 2002). Along with prolactin and OT, AVP pre-
systems involved in the expression of maternal care. pares the male to be receptive to and care for infants
The HPA system of offspring during development is (Bales et al., 2004).
influenced by variation in maternal care, which then Paternal care is more common in monogamous
influences their maternal behavior as adults. Such than polygamous mammals and is often related to
changes involve the production of, and receptor dens- hormonal and behavioral stimuli from the female.
ity for, stress hormones and OT (Champagne and In the monogamous California mouse, disruption of
Meaney, 2001; Fleming et al., 1999). the pair bond does not affect maternal care but does
The HPA-modulated hormones and maternal diminish paternal care (Gubernick, 1996). In other
behavior are related in humans during the postpartum species with biparental care, however, paternal care is
period (Fleming et al., 1997). During this time, cortisol not as dependent on the presence of the female (Young
appears to have an arousal effect, focusing attention on and Insel, 2002). Experience also plays a role in influ-
infant bonding. Mothers with higher cortisol levels encing hormonal activation and paternal behavior.
were found to be more affectionate, more attracted to Among tamarins, experienced fathers have higher
their infant’s odor, and better at recognizing their levels of prolactin than first-time fathers (Ziegler and
infant’s cry during the postpartum period. Snowdon, 1997).
Functional magnetic resonance imaging (fMRI) Androgens including testosterone also appear to be
studies of brain activity involved in maternal attach- involved in the regulation of paternal behavior. For
ment in humans indicate that the activated regions are example, human fathers tend to have lower testoster-
part of the reward system and contain a high density of one levels when they are involved in childcare activities
receptors for OT and AVP (Bartels and Zeki, 2004; (Berg and Wynne-Edwards, 2002; Fleming et al., 2002;
Gray and Campbell, 2009; also see Chapter 16 of this pair and larger family network, it is not surprising that
volume), although the relation with the key paternal similar neurohormonal mechanisms active in the
role of offspring protection is uncertain. Human males maternal–offspring bond would also be selected to
stand out as very different from our closest relatives underlie these other attachments. Though there is
the chimpanzees in the areas of paternal attachment some variation among species and between males and
and investment in offspring. Investigation of the neu- females, the same general neurohormonal systems
roendocrine mechanisms that underpin male parental active in pair bonding in other species are found in
behavior may provide important insights into these the human (Wynne-Edwards, 2003; Panksepp, 2004;
critical evolutionary changes. Lee et al., 2009). Androgen response to pair bonding
appears complex (e.g. van der Meij et al., 2008), but
similar to parent–offspring attachment in that pair
Pair bonding
bonded males tend to have lower testosterone levels
Like male parental care, bonding between mates is also in nonchallenging conditions (Alvergne et al., 2009;
uncommon among mammals but has been selected for Gray and Campbell, 2009). Moreover, males actively
when it has reproductive advantages for both parents involved in caretaking behavior appear to have tempor-
(Clutton-Brock, 1991; Carter, 2002; Young et al., 2002). arily diminished testosterone levels (Gray et al., 2007).
Monogamy is found across many mammalian taxa, The challenge before human evolutionary biolo-
but most of the current knowledge related to the neu- gists and psychologists is to understand how these
roendocrine basis of this phenomenon has been general neuroendocrine systems have been modified
obtained from the comparative study of two closely and linked with other special human cognitive systems
related rodent species. The prairie vole (Microtus (e.g., Allman et al., 2001; Blakemore et al., 2004) to
ochrogaster) mating pair nest together and provide pro- produce the unique suite of human family behaviors.
longed biparental care, while their close relatives, the Analysis of hormonal responses to social stimuli may
meadow vole (Microtus pennsylvanicus), do not exhibit provide important insights into the selective pressures
these behaviors (Young et al., 2002). As with other that guided the evolution of these key aspects of the
social behaviors in rodents, OT and AVP have been human mind.
found to be central in the differences these related
species exhibit with respect to pair bonding.
The chemistry of stress, family, and the social mind
Pair bonding occurs for the prairie vole following
mating. Vagino-cervical stimulation results in a release The evolutionary scenario proposed in previous
of OT and the development of a partner preference for sections posits that the family is of paramount import-
the female (Carter, 2002). For the male, it is an increase ance in a child’s world. Throughout human evolution-
in AVP following mating and not just OT that results in ary history, parents and close relatives provided
partner preference. Exogenous OT injected in the calories, protection, and information necessary for sur-
female and exogenous AVP in the male prairie vole vival, growth, health, social success, and eventual
result in mate preference even without mating. This reproduction. The human mind, therefore, is likely to
does not occur with meadow voles (Young et al., 2002). have evolved special sensitivity to interactions with
The receptor density for OT and AVP in specific family care providers, particularly during infancy and
brain regions might provide the basis for mechanisms early childhood (Bowlby, 1969; Baumeister and Leary,
underlying other social behaviors. Other neurotrans- 1995; Daly and Wilson, 1995; Belsky, 1997, 1999; Geary
mitters, hormones, and social cues also are likely to and Flinn, 2001; Flinn et al. 2009).
be involved, but slight changes in gene expression for The family and other kin provide important cogni-
receptor density, such as those found between the tive “landmarks” for the development of a child’s
meadow and prairie voles in the ventral palladium understanding of the social environment. The repro-
(located near the nucleus accumbens, an important ductive interests of a child overlap with those of its
component of the brain’s reward system), might dem- parents more than with any other individuals. Infor-
onstrate how such mechanisms could be modified mation (including advice, training, and incidental
by selection (Lim et al., 2004). The dopamine D2 recep- observation) provided by parents is important for situ-
tors in the nucleus accumbens appear to link the ating oneself in the social milieu and developing a
affiliative OT and AVP pair bonding mechanisms with mental model of its operations. A child’s family envir-
positive rewarding mental states (Aragona et al., 2003; onment may be an especially important source and
Curtis and Wang, 2003). The combination results in mediator of stress, with consequent effects on health.
the powerful addiction that parents have for their Psychosocial stressors are associated with
offspring. increased risk of infectious disease (Cohen et al.,
Given the adaptive value of extensive biparental 2003) and a variety of other illnesses (Ader et al.,
care and prolonged attachment found in the mating 2001). Physiological stress responses regulate the
414 Mark V. Flinn
allocation of energetic and other somatic resources functions. The demands of energy regulation must
to different bodily functions via a complex assortment orchestrate with those of immune function, attach-
of neuroendocrine mechanisms. Changing, unpredict- ment bonding, and so forth. Mechanisms for localized
able environments require adjustment of priorities. targeting (e.g., glucose uptake by active versus inactive
Digestion, growth, immunity, and sex are irrelevant muscle tissues and neuropeptide-directed immune
while being chased by a predator (Sapolsky, 1994). response) provide fine-tuning of the preceding general
Stress hormones help shunt blood, glucose, and so physiological effects. Cortisol regulation allows the
on to tissues necessary for the task at hand. Chronic body to respond to changing environmental conditions
and traumatic stress can diminish health, evidently by preparing for specific short-term demands (Mason,
because resources are diverted away from important 1971; Munck et al., 1984; Weiner, 1992).
health functions. These costs can be referred to as These temporary beneficial effects of glucocorti-
“allostatic load” (McEwen, 1995). Such diversions of coid stress response, however, are not without costs.
resources may have special significance during child- Persistent activation of the HPA system is associated
hood because of the additional demands of physical with immune deficiency, cognitive impairment,
and mental growth and development and possible inhibited growth, delayed sexual maturity, damage to
long-term ontogenetic consequences. the hippocampus, and psychological maladjustment
(Glaser and Kiecolt-Glaser, 1994; Dunn, 1995;
McEwen, 1995; Ader et al., 2001). Chronic stress may
Stress response mechanisms and theory
diminish metabolic energy (Ivanovici and Wiebe, 1981;
Physiological response to environmental stimuli per- Sapolsky, 1991) and produce complications from
ceived as stressful is modulated by the limbic system autoimmune protection (Munck and Guyre, 1991).
(amygdala and hippocampus) and basal ganglia. These Stressful life events – such as divorce, death of a
components of the CNS interact with the sympathetic family member, change of residence, or loss of a job –
and parasympathetic nervous systems and two neu- are associated with infectious disease and other
roendocrine axes, the sympathetic-adrenal medullary health problems (Herbert and Cohen, 1993; Maier
system (SAM) and the HPA. The SAM and HPA systems et al., 1994).
affect a wide range of physiological functions in con- Current psychosocial stress research suggests that
cert with other neuroendocrine mechanisms and cortisol response is stimulated by uncertainty that is
involve complex feedback regulation. The SAM system perceived as significant and for which behavioral
controls the catecholamines norepinephrine and epi- responses will have unknown effects (Weiner, 1992;
nephrine (adrenalin). The HPA system regulates gluco- Kirschbaum and Hellhammer, 1994). That is, import-
corticoids, primarily cortisol (for reviews, see Weiner, ant events are going to happen; the child does not
1992; McEwen, 1995; Sapolsky et al., 2000). know how to react but is highly motivated to figure
Cortisol is a key hormone produced in response to out what should be done. Cortisol release is associated
physical and psychosocial stressors (Mason, 1968; with unpredictable, uncontrollable events that require
Selye, 1976). It is produced and stored in the adrenal full alert readiness and mental anticipation. In appro-
cortex. Release into the plasma is primarily under the priate circumstances, temporary moderate increases in
control of pituitary adrenocorticotropic hormone stress hormones (and associated neuropeptides) may
(ACTH). The free or unbound portion of the circulating enhance mental activity for short periods in localized
cortisol may pass through the cell membrane and bind areas, potentially improving cognitive processes for
to a specific cytosolic glucocorticoid receptor. This responding to social challenges (Beylin and Shors,
complex may induce genes coding for at least 26 differ- 2003; Lupien, 2009). Other mental processes may be
ent enzymes involved with carbohydrate, fat, and inhibited, perhaps to reduce external and internal
amino acid metabolism in brain, liver, muscle, and “noise” (Servan-Schreiber et al., 1990; cf. Newcomer
adipose tissue (Yuwiler, 1982). et al., 1994).
Cortisol modulates a wide range of somatic func- Relations between cortisol production and emo-
tions, including: (1) energy release (e.g., stimulation of tional distress, however, are difficult to assess
hepatic gluconeogenesis in concert with glucagon and because of temporal and interindividual variation in
inhibition of the effects of insulin); (2) immune activity HPA response (Kagan, 1992; Nachmias et al., 1996).
(e.g., regulation of inflammatory response and the Habituation may occur to repeated events for
cytokine cascade); (3) mental activity (e.g., alertness, which a child acquires an effective mental model.
memory, and learning); (4) growth (e.g., inhibition of Attenuation and below-normal levels of cortisol may
growth hormone and somatomedins); and (5) repro- follow a day or more after emotionally charged events.
ductive function (e.g., inhibition of gonadal steroids, Chronically stressed children may develop abnormal
including testosterone). These complex multiple effects cortisol response, possibly via changes in binding
of cortisol muddle understanding of its adaptive globulin levels and/or reduced affinity or density of
glucocorticoid or corticotrophin-releasing hormone

(CRH)/vasopressin receptors in the brain (Fuchs and
Flugge, 1995). Early experience – such as perinatal
Cortisol (standardized)
stimulation of rats (Meaney et al., 1991), prenatal
0.5
stress of rhesus macaques (Schneider et al., 1992;
Clarke, 1993), and sexual abuse among humans (de
Bellis et al., 1994) – may permanently alter HPA
0
response. Personality may also affect HPA response
(and vice versa) because children with inhibited tem-
peraments tend to have higher cortisol levels than
–0.5
extroverted children (Kagan et al., 1988; cf. Gunnar
Mom Single Grand- Single Distant Step-
et al., 1995; Hertsgaard et al., 1995; Nachmias et al., and dad mom parents mom relatives family
1996). and kin
Further complications arise from interaction Household compoistion
between the HPA stress response and a wide variety
24.1. Cortisol levels and household composition of children
of other neuroendocrine activities, including modula- living in Bwa Mawego, Dominica. Box and whisker plots are for
tion of catecholamines, melatonin, testosterone, children’s mean values of cortisol standardized for time since
serotonin, b-endorphins, cytokines, and enkephalins awakening (for descriptions of methods see Flinn 2006b).
(de Kloet, 1991; Sapolsky, 1992; Saphier et al., 1994). Double lines represent average cortisol levels when an absence
of stressful events were observed or reported. Stars indicate
Changes in cortisol for energy allocation and modula-
average cortisol levels during holidays (day before Christmas
tion of immune function may be confused with and August holiday weekends). Data include 21 673 salivary
effects of psychosocial stress. As reviewed in the previ- cortisol samples from 268 children collected from 1989–2001.
ous section, OT and vasopressin intracerebral binding
sites are associated with familial attachment in
mammals and may influence distress involving effects of naturally occurring psychosocial events in
caretaker–child relationships. Other components of the family environment.
the HPA axis such as CRH and melanocyte-stimulating Associations between average cortisol levels of
hormone have effects that are distinct from cortisol. children and household composition indicate that
children living with nonrelatives, stepfathers, and
half-siblings (stepfather has children by the stepchild’s
Stress response and family environment
mother), or single parents without kin support had
Composition of the family or caretaking household higher average levels of cortisol than children living
may have important effects on child development with both parents, single mothers with kin support,
(Kagan, 1984; Whiting and Edwards, 1988). For or grandparents (Figure 24.1). Note, however, that
example, in Western cultures, children with divorced these differences in cortisol levels are diminished when
parents may experience more emotional tension or comparisons are made during nonstressed conditions
“stress” than children living in a stable two-parent (double line bars in Figure 24.1). Moreover, the pattern
family (Wallerstein, 1983; Pearlin and Turner, 1987; is reversed during the excitement of holidays and other
Gottman and Katz, 1989). apparently hedonic emotional circumstances (stars in
Investigation of physiological stress responses in Figure 24.1). Hence cortisol appears to be elevated
the human family environment has been hampered during “positive” as well as “negative” social
by the lack of noninvasive techniques for measurement challenges.
of stress hormones. Frequent collection of plasma A further test of the hypothesis that difficult family
samples to assess temporal changes in endocrine func- environments are stressful is provided by comparison
tion is not feasible in nonclinical settings. The develop- of step- and genetic children residing in the same
ment of saliva immunoassay techniques, however, households. Stepchildren had higher average cortisol
presents new opportunities for stress research. Saliva levels than their half-siblings residing in the same
is relatively easy to collect and store, especially household who were genetic offspring of both parents
under adverse field conditions faced by anthropolo- (Figure 24.2).
gists (Ellison, 1988). In this section I review results Several caveats need emphasis. Firstly, not all chil-
from a longitudinal, 20-year study of child stress and dren in difficult family environments have elevated
health in a rural community on the island of Dominica cortisol levels. Secondly, household composition is
(for reviews see Flinn and England, 1995, 1997, 2003; not a uniform indicator of family environment.
Flinn, 1999, 2006b). The research design uses concomi- Some single-mother households, for example, appear
tant monitoring of a child’s daily activities, stress hor- more stable, affectionate, and supportive than some
mones, and psychological conditions to investigate the two-parent households. Thirdly, children appear
416 Mark V. Flinn
1 whereas calm, affectionate contact was associated

with diminished (–10% to –50%) cortisol levels. Of
Cortisol (standardized) all cortisol values that were more than two standard
deviations (2 SD) above mean levels (i.e., indicative
of substantial stress), 19.2% were temporally associ-
ated with traumatic family events (residence change
0
of child or parent/caretaker, punishment, “shame,”
serious quarreling, and/or fighting) within a 24-hour
period. In addition, 42.1% of traumatic family events
were temporally associated with substantially elevated
Genetic Step-
–1 offspiring
cortisol (i.e., at least one of the saliva samples collected
offspring
(N = 25) (N = 27) within 24 hours was > 2 SD above mean levels).
Chronic elevations of cortisol levels sometimes
24.2. Comparison of cortisol levels (standardized for time since
awakening) of children (maternal half-siblings) living in the same occurred among children in difficult family environ-
household that were either genetic offspring or step-offspring of ments, but this was difficult to assess quantitatively
the resident adult male. (Flinn, 2009).
There was considerable variability among children
differentially sensitive to different aspects of their car- in cortisol response to family disturbances. Not all
etaking environments, reflecting temperamental and individuals had detectable changes in cortisol levels
other individual differences. associated with family trauma. Some children had
These caveats, however, do not invalidate the significantly elevated cortisol levels during some epi-
general association between household composition sodes of family trauma but not during others. Cortisol
and childhood stress. There are several possible response is not a simple or uniform phenomenon.
reasons underlying this result. Children in difficult Numerous factors, including preceding events, habitu-
caretaking environments may experience chronic ation, specific individual histories, context, and tem-
stress resulting in moderate-high levels of cortisol perament, might affect how children respond to
(i.e., a child has cortisol levels that are above average particular situations.
day after day). They may experience more acute stres- Nonetheless, traumatic family events were associ-
sors that substantially raise cortisol for short periods ated with elevated cortisol levels for all ages of
of time. They may experience more frequent stressful children more than any other factor that we exam-
events (e.g., parental chastisement or marital quarrel- ined. These results suggest that family interactions
ling – see Wilson et al., 1980; Flinn, 1988; Finkelhor were a critical psychosocial stressor in most children’s
and Dzuiba-Leatherman, 1994) that temporarily raise lives, although the sample collection during periods
cortisol. There may be a lack of reconciliation between of intense family interaction (early morning
parent and child. And they may have inadequate and late afternoon) may have exaggerated this
coping abilities, perhaps resulting from difficult association.
experiences in early development. Although elevated cortisol levels are associated
The events in children’s lives that are associated with traumatic events such as family conflict, long-
with elevated cortisol are not always traumatic or term stress may result in diminished cortisol response.
even “negative.” Activities such as eating meals, hard In some cases, chronically stressed children had
physical work, routine competitive play (e.g., cricket, blunted response to physical activities that normally
basketball, and “king of the mountain” on ocean evoked cortisol elevation. Comparison of cortisol
rocks), return of a family member that was temporarily levels during “nonstressful” periods (no reported or
absent (e.g., father returning from a job in town for observed crying, punishment, anxiety, residence
the weekend), and holiday excitement (stars in change, family conflict, or health problem during
Figure 24.1) were associated with temporary moderate 24-hour period before saliva collection) indicates a
increases (from about 10% to 100%) in cortisol among striking reduction and, in some cases, reversal of the
healthy children. These moderate stressors usually had family environment–stress association (see double bars
rapid attenuation (<1 hour) of cortisol levels (some in Figure 24.1). Chronically stressed children some-
stressors had characteristic temporal “signatures” of times had subnormal cortisol levels when they were
cortisol level and duration). not in stressful situations. For example, cortisol levels
High-stress events (cortisol increases from 100% to immediately after school (walking home from school)
2000%), however, most commonly involved trauma and during noncompetitive play were lower among
from family conflict or change (Flinn et al., 1996; Flinn some chronically stressed children (cf. Long et al.,
and England, 2003). Punishment, quarreling, and resi- 1993). Some chronically stressed children appeared
dence change substantially increased cortisol levels, socially “tough” or withdrawn and exhibited little
or no arousal to the novelty of the first few days of the critical selective pressure. In Bwa Mawego, and
saliva collection procedure. perhaps in most human societies, children elevate their
Relations between family environment and cortisol stress hormone (cortisol) levels more frequently and
stress response appear to result from a combination extensively in response to psychosocial stimuli than
of factors including frequency of traumatic events, to challenges associated with the physical environ-
frequency of positive “affectionate” interactions, fre- ment. The adaptive effects of the major stress hor-
quency of negative interactions such as irrational pun- mones (Huether, 1996, 1998; Koolhaas et al., 2006;
ishment, frequency of residence change, security of Fox et al., 2007) and affiliative neurotransmitters on
“attachment,” development of coping abilities, and neural reorganization appear consistent with observa-
availability or intensity of caretaking attention. tions of sensitivity to the social world (Flinn, 2006b).
Probably the most important correlate of household Social competence is extraordinarily difficult
composition that affects childhood stress is maternal because the competition is constantly changing
care. Mothers in socially “secure” households (i.e., per- and similarly equipped with ToM and other cognitive
manent amiable coresidence with mate and/or abilities. The sensitivity of the stress-response and
other kin) appeared more able and more motivated affiliative systems to the social environment may
to provide physical, social, and psychological care for enable adaptive neural reorganization to this most
their children. Mothers without mate or kin support salient and dynamic puzzle. Childhood appears neces-
were likely to exert effort attracting potential mates sary and useful for acquiring the information and
and may have viewed dependent children as impedi- practice to build and refine the mental algorithms
ments to this. Hence coresidence of father may provide critical for negotiating the social coalitions that
not only direct benefits from paternal care but also are the key to success in our species. The human
may affect maternal care (Lamb et al., 1987; Belsky family provides critical support for the child to develop
et al., 1991; Flinn, 1992; Hurtado and Hill, 1992). sociocognitive skills. Traumatic early environments
Young mothers without mate support usually relied may result in diminished abilities to acquire social
extensively on their parents or other kin for help with competencies as a consequence of glucocorticoid
child care. hypersensitivity disrupting neurogenesis, particularly
Children born and raised in household environ- in the hippocampus and other components of the
ments in which mothers have little or no mate or limbic system (Mirescu et al., 2004; Weaver et al.,
kin support were at greatest risk for abnormal cortisol 2004). An improved understanding of the hormonal
profiles and associated health problems. Because and neurological mechanisms that facilitate the inten-
socioeconomic conditions influence family environ- sive and extensive relationships involved with
ment, they have consequences for child health that human families and broader kin coalitions, including
extend beyond direct material effects. Also, because comparisons between humans and our close primate
health in turn may affect an individual’s social and relatives, may provide important insights into the
economic opportunities, a cycle of poor health and selective pressures that shaped key features of human
poverty may be perpetuated generation after biology.
generation.
DISCUSSION POINTS
CONCLUDING REMARKS
1. What happened to our hominin ancestors?
People in difficult or inequitable social environments Why are we the only species left? If humans sud-
tend to be less healthy in comparison with their more denly went extinct, would another life form even-
fortunate peers (e.g., Flinn, 1999; Hertzman, 1999; tually evolve high intelligence? How?
Dressler and Bindon, 2000; Wilkinson, 2001; Cohen 2. Do you think chimpanzee fathers love their off-
et al., 2003;). Social support can have reproductive spring? Why or why not? And chimpanzee
consequences in group-living species (e.g., Silk et al., grandparents?
2003; Cheney and Seyfarth, 2007). If the brain evolved 3. Do school exams make you sick? Collect data from
as a social tool, then the expenditure of somatic your classmates to test your hypotheses.
resources (e.g., glucose) to resolve psychosocial prob- 4. What events cause you to become “stressed”? Why
lems makes sense. Relationships, especially family do you think natural selection produced psycho-
relationships, are of paramount importance. They are logical mechanisms that result in this sensitivity?
likely to have been a key factor affecting human repro- 5. How are the events that cause stress for you similar
ductive success at least for over half a million years, and/or different from the events that were stressful
and selection may have shaped our hormonal, neural, for your parents, your grandparents, and your dis-
and psychological mechanisms to respond to this tant hominin ancestors?
418 Mark V. Flinn
Bartels, A. and Zeki, S. (2004). The neural correlates of

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25 Human Biology, Energetics,
and the Human Brain
Benjamin C. Campbell
INTRODUCTION of behavior, the brain seems to have an almost infin-

itely flexible phenotypic expression. In contrast, the
Human biology has made great progress in applying standard methods of human biology focus on the
modern techniques to the understanding of human measurement of relatively simple phenotypes such as
biological variation at the genetic, physiological, devel- the size and shape of anatomical features and variation
opmental, and phenotypic levels. For instance, rather in their developmental timing. These can be easily
than only asking about disease symptoms, human quantified using methods suitable for the field and
biologists measure immune makers which represent compared across populations.
an underlying element of health (McDade et al., 2005; However, in terms of the brain, simple and robust
Muehlenbein et al., 2005; Snodgrass et al., 2007); phenotypes are hard to come by. Measures of brain
rather than simply measuring body fat, they determine size and shape are not accessible in the samples of
leptin levels as a signal of energy stores (Bribiescas, living human beings favored by human biologists, even
2005). In addition to collecting self-reports of stress, if we knew how to interpret them. On the other hand,
they assay for salivary cortisol (Pike and Williams, proxy measures such as skull size and shape are emi-
2006; Nepomnaschy et al., 2006). Along with collecting nently measurable, but variation across human popu-
reproductive histories, they measure gonadal steroids lations reflect climatic variation, not brain function
including estrogen, progesterone (Lipson and Ellison, (Beals et al., 1984).
1996), and testosterone (Campbell et al., 2006). Thus some other simple and robust metric for
At the same time, human biologists have also measuring brain function is necessary. An energetic
become more evolutionarily sophisticated as they have approach has at least two advantages. Firstly, the brain
adopted a life history perspective (Hill, 1993; Kuzawa, is energetically expensive with 2% of body mass using
2007). There is a growing understanding that much of 20% of energy among humans (Elia, 1992), increasing
the variation in the phases of the life cycle, starting in the probability of selection based on energetic con-
utero, and moving through childhood, adolescence, straints. These include trade-offs within the brain itself
adulthood, and aging represents an inter-related as well as somatic maintenance and growth as outlined
response to energetic availability. The impact of nutri- by life history theory. Secondly, an energetic perspec-
tion during fetal development, in particular may have tive is consistent with an emerging focus on energetics
important implications for the rest of the life cycle in human evolution more generally (Ailleo and
(Jasienska et al., 2006; Kuzawa, 2007). Furthermore, Wheeler, 1995; Leonard and Ulijaszek, 2002; Leonard
the understanding that growth and development, et al., 2007).
immune function, and reproductive function are In what follows I attempt to provide a sufficient
responsive to energetics means that human biologists outline of human brain metabolism, including energy
can use energy as a currency through which the basic utilization, storage, and substrate availability, and its
functions of growth, maintenance, and reproduction association with brain development to be able to con-
can be traded off (Hill, 1993). sider its implications for human evolution. In the first
Yet human biologists have tended to avoid studying part of the paper, I set the stage with a brief review of
the brain (see Leonard et al., 2003, 2007 for an excep- earlier work on brain metabolism and evolution. I then
tion). Such shyness surely reflects the Cartesian review recent advances in assessing energy utilization
dichotomy, in which the mind and body are fundamen- in the brain which highlight the intrinsic and intimate
tally different spheres and hence must be studied using interplay between energetic utilization and neuronal
different techniques. At the same time, it may also function. I argue that the elevated energetic costs of
reflect the shear complexity of the brain. As the organ the human brain are balanced against the benefit
425
426 Benjamin C. Campbell
of increased neuroplasticity. I suggest that glucose OVERVIEW OF ENERGETICS

utilization in the human brain is directly tied to synap- AND THE BRAIN
tic plasticity through a process referred to as glutamate
cycling, and that a high glutamate flux is important in It is well known to human biologists that the brain is
to human neuroplasticity. an energetically expensive organ, consuming 20% of
In the second part of the paper I review the recent the body’s energy, despite being only 2% of the body’s
literature showing changes in the energetic utilization weight (Elia, 1992). But this figure only superficially
of the human brain during development. I argue that reflects how pervasive the effects of energetic factors
changes in energy utilization in the developing brain are in brain function. The brain depends almost
are closely tied to on-going processes of brain develop- entirely on glucose as a metabolic fuel (Van Itallie
ment. More specifically, I suggest that age-related and Nufert, 2003) and accounts for 50% of total body
changes in glucose utilization (Chugani, 1998) are con- glucose utilization (Fehm et al., 2006). Furthermore,
sistent with development patterns of neuroplasticity, brain structures such as the hippocampus and amyg-
social context, and behavioral development in humans. dala known for their role in basic functions of memory
I hope to show that rather than representing a release and emotional regulation are also important in regula-
from energetic constraints, the development of the tion of somatic energy use and food intake (Fehm et al.,
human brain becomes a focal point for the selective 2006). Thus, brain activity is only tied to energy con-
power of energetic constraints during evolution. sumption, but with regulating its own energy status
(Peters et al., 2004).
In order to understand the role of metabolism in
HISTORICAL BACKGROUND brain function, it is useful to first characterize the
brain on a more global level. Neurobiologists list
Early interest in human brain metabolism and evolu- several qualities of the brain that may be important.
tion grew out of attempts to understand the basis for These include: (1) the brain is very plastic, i.e.,
the allometric relationship between brain and body capable of changing; (2) it has little storage, i.e.,
across mammals (Martin, 1981; Armstrong, 1983, there is little evidence for glycogen storage in
1985). When the scaling coefficient of brain to body neurons; (3) is substrate specific, i.e., it will only
size was thought to be around 0.67, it was suggested to metabolize glucose; (4) is separated from the body
reflect the relationship between neural sensory input/ by the blood–brain barrier reducing its exposure to
output function and body surface area. However, Arm- the general circulation (Peters et al., 2004). To these
strong (1983) demonstrated that variation in brain size I would add: (5) the brain is energetically demanding
across mammals is related to the relative amount of (Armstrong, 1985; Fehm et al., 2006), i.e., it is always
energy utilized by the brain, i.e., its scales with the active and can not survive long if its energy supply
amount of energy reserves (Armstrong, 1985), clearly is interrupted.
suggesting the important of metabolism in brain evo- Brain function is a metabolically dynamic process,
lution. Interestingly Crile (1941) had anticipated the with specific brain activity dependent on increased
importance of metabolism in brain evolution and energy utilization (Shulman et al., 2004). Neural plas-
argued that the importance of basal metabolism to ticity, the alteration of neural connections based on
brain size must have coevolved with the thyroid experience, enhances the ability of the brain to adapt
function. to the environmental by directing that energy toward
When other analyses indicated that the scaling the most commonly used neuronal pathways and
coefficient was closer to 0.75, than 0.67, arguments neural circuits. In contrast, the other four qualities
about body surface area no longer made sense. Instead, listed above; energetically demanding, little storage,
Martin (1981) suggested that the underlying relation- substrate specificity, and the blood–brain barrier, all
ship might reflect constraints on maternal metabolic act to limit the physiological range in which the brain
investment in fetal brain development. More specific- can operate. Thus the trade-off between energy and
ally, in terms of human evolution, Martin (1989) has brain function in humans can been seen as a basic
argued that australopithecines demonstrate increased function of energy utilization and the maintenance of
brain to body size ratios relative to the great apes. He neural plasticity.
then suggests that a reduction in gut along with an The cellular basis of both energy utilization
increase in high quality food would have been neces- and neural plasticity has come into clearer focus
sary to allow for the increased the energetic demands in recent years. Though still controversial (Pellerin
of the brain. It is this idea that was taken up by Aiello et al., 2007), recent findings have been taken to
and Wheeler (1995) and dubbed the “expensive tissue suggest a metabolic cycle between astrocytes and
hypothesis.” In what follows I explore in more detail neurons in which glucose is used by astrocytes
why the brain is expensive tissue. to convert glutamate to glutamine. In the process
Human Biology, Energetics, and the Human Brain 427
glucose is transformed into lactate which is ENERGY CONSUMPTION AND

consumed by neurons (Magistretti, 2006). This tight BRAIN ACTIVITY
metabolic coupling of neurons and astrocytes,
referred to as the astrocyte-lactate neuronal shuttle Before considering the implications of specific
appears central to understanding brain plasticity. aspects of energy metabolism for brain function, it
Glutamate is critical to neuronal plasticity and its is important to outline the processes that contribute
association with glucose directly links energetic pro- to the total energetic costs of the brain. The develop-
cesses and neural plasticity throughout the lifecycle ment of functional magnetic resonance imaging
(Magistretti, 2006). In fact, Ulian et al. (2004) have (fMRI) has focused attention on energy utilization
suggested that astrocytes should be understood as during the activation of particular brain regions
regulators of synaptic plasticity. (Shulman et al., 2004). However, such functional
Furthermore, it is now clear on the basis of both activation appears to represent a remarkably small
animal models (Gruetter, 2003; Brown, 2004) and fraction of the total energy consumed by the adult
human studies (Oz et al., 2007) that the brain does in human brain (Raichle and Mintun, 2006). Based
fact have important glycogen stores, albeit at much on both glucose and blood utilization studies it is
lower levels than found in other tissues such as muscle. estimated that activation of neuronal processes
Such stores appear to vary across regions of the brain accounts for some 1% of energy utilization in the
and are most abundant in more metabolically active brain (Raichle and Mintum, 2006), the other 99%
parts of the brain such as the hippocampus (Dalsgaard of the brain energy consumption is related to base-
et al., 2007). Thus glycogen is more likely to represent a line or “resting” activity levels. Only 15% of total
local energy buffer during normal use (Brown, 2004; brain energy consumption is thought to be related
Brown and Ransom, 2007) than storage against patho- to the maintenance of resting action potentials
logical conditions such as global ischemia, as previ- and glial cell activity (Attwell and Laughlin, 2001),
ously assumed. leaving approximately 80% of brain energy consu-
While the blood–brain barrier remains an mption devoted to something else (Raichle and
important reality and glucose is the major energy Gusnard, 2002).
source transported across the blood–brain barrier That something else has been referred to as
(Peters et al., 2004), other substrates such as intrinsic brain activity (Raichle and Mintum, 2006).
ketones and lactate can cross the blood–brain Intrinsic brain activity is not well defined, but is
barrier (Emery, 2005), and may serve physiologically thought to represent a default brain system (Raichle
important functions in addition to their role as et al., 2001) that is attenuated but not deactivated
energy substrates. For instance, ketones appear to during a conscious task. Furthermore, this brain
be important during early development when they system appears to show spontaneous cycles of energy
are an important substrate in the production of usage suggesting it is dynamically active (Fox et al.,
lipids by oligodendrocytes (Edmond, 1992; Nehlig, 2005; Mantini et al., 2007). The function of such a
2004), including lipids associated with myeliniza- brain system may reflect stimulus independent
tion, so important to early brain development. In thought (Mason et al., 2007 and may involve somatic
another example, transport of lactate into the brain self-monitoring (Raichle et al., 2001) and the process-
is particularly important during exercise (Dalsgaard, ing of episodic memory (Greicius et al., 2003; Greicius
2006), suggesting that the brain does not always and Menon, 2004). Similar brain activity appears
have total priority for glucose utilization and physio- to occur during sleep, making intrinsic brain activity
logical mechanisms other than glucose metabolism on-going and independent of wakefulness (Horovitz
may play a role in adjusting the allocation of energy et al., 2007).
between the brain and body. High levels of on-going brain activity suggest that
Finally, there is growing evidence that the brain the energetic demands of the brain are both constant
has cells that sense glucose (Rao et al., 2006) and and dynamic. I argue that such high energy utiliza-
react accordingly, allocating energy to the brain tion and glucose dependence is directly related to
depending on its needs. Peters et al. (2004) have synaptic plasticity at the cellular level, through the
argued that because the brain has priority of alloca- process of glutamate cycling (Shulman et al., 2004;
tion and controls other parts of the body, it is in Magistretti, 2006). Glutamate cycling appears to run
control of its own energetic requirements. From a at a higher rate in the brain of humans and great
life history perspective, such a “selfish brain” should apes relative to other primate relatives (Burki and
include potential mechanisms for shifting allocation Kaessmann, 2004), thus allowing for higher local
of energy to brain versus the body as the importance energy utilization and potentially greater neural plas-
of the brain relative to reproduction shifts over the ticity. I elaborate the physiological details of this
life course. argument below.
The astrocycte-neuron-lactate shuttle The basis for the development of new synapses is
not fully understood. However, N-methyl-D-aspartate
Recent work has suggested that most neurons do not
(NMDA) receptors appear to be involved. In the case of
metabolize glucose directly, but obtain their energy
dopaminergic neurons, NMDA receptors are important
through an interaction with surrounding glial cells, a
in trapping D1 dopamine receptors into synapses
process referred to as the astrocyte-neuron-lactate
(Scott et al., 2002), thus creating a dopaminergic syn-
shuttle (Bittar et al., 1996; Pellerin et al., 1998). As part
apse. Since NMDA is a glutamate receptor, increased
of this cycle, glutamate released into the synapse is
glutamate flux may act to promote the stabilization of
taken up by a glutamate transporter (EAAT2) and
dendritic dopaminergic synapses. In addition, NMDA
brought into astrocytes surrounding the synapse.
receptors are thought to be particularly important
There glucose is used to convert glutamate to glutam-
in the growth of dendritic spine during long-term
ine through the act of glutamine synthetase (Daikhan
potentiation (LTP) (Park et al., 2006), a basic neural
and Yudkoff, 2000). The glutamine produced in the
mechanism underlying learning.
astrocyte is then taken up by the neuron. In the
Regardless of the exact cellular mechanisms invol-
process, lactate is created within the astrocyte which
ved in neural plasticity, it is clear that glutamate
is later taken up by the neuron and used to reconvert
cycling is very important in terms of brain energetics.
the glutamine to glutamate for release in the synapse
Ninety percent of synapses release glutamate (Abeles,
(Magistretti, 2006). In addition to glutamate, a small
1991; Braitenberg and Schuz, 1998), a figure that
fraction of the glutamine is converted into gamma-
reflects the corelease of neurotransmitters by individ-
butyric acid (GABA) the major inhibitory transmitter
ual neurons (Trudeau and Gutiérrez, 2007). Eighty
in the brain (Patel et al., 2005).
percent of the utilization of glucose is linearly related
As mentioned previously, the function of glutamate
to glutamate cycling (Sibson et al., 1998; Shen et al.,
cycling has not been fully established, though it is been
1999). In addition, it has been estimated that about
suggested as the basis for neural plasticity (Magistretti,
20% of the energy consumed by glutamate cycling is
2006). It is generally thought that a build up of glutam-
used in the production of GABA (Patel et al., 2005),
ate from the synapse into the extracellular space
giving this neurotransmitter a smaller, but still poten-
decreases the signal-to-noise ratio in the synapse and
tially important, role in the relationship between
at extreme levels can lead to axonal depolarization and
energy consumption and brain function.
the death of neurons. By removing glutamate from the
The importance of glutamate in human brain
synapse and metabolizing it within the astrocyte
metabolism is illustrated by the recent discovery of a
neurons are less susceptible to glutamate excitotoxicity,
hominoid specific version of the glutamate dehydro-
allowing for increased strengthening of synaptic con-
genase gene (GLUD). GLUD2 is a variant of GLUD
nections on the basis of neuronal firing and experience.
found only in humans and the great apes (Burki and
Rocher et al. (2003) show that levels of snyap-
Kaessman, 2004) resulting in an increased capacity to
tophysin, a marker of synaptic density, are related to
oxidize glutamate under low oxygen conditions (Plai-
regional glucose utilization in baboons, supporting the
takis et al., 2003), indicative of increased glutamate
idea that glucose metabolism is associated with neural
turnover. Since neural plasticity is based on the
connectivity. Thus the high rate of glucose utilization
maintenance of synaptic connections, increased glu-
of the human brain may translate directly into the
tamate cycling among both humans and the great apes
benefits of synaptic plasticity.
may be associated with a greater capacity for neural
At the cellular level, synaptic plasticity is known to
plasticity than other primates.
be associated with the growth and development of
dendrites and dendritic spines (Calabrese et al.,
2006). A greater proliferation of dendrites allows more
Energetics in specific parts of the brain
room for dendritic spines. Since many synapses form
on dendrite spines, more dendrites spines allow for Given that 90% of all neurons express glutamate,
more synapses as well. However, it is only recently that glutamate cycling can be expected to play a role in
the dynamic nature of dendritic spine development has maintaining neural plasticity throughout the brain.
become clear. Small filaments on the dendrites emerge However, given its association with glucose utilization,
and start to grow to larger filaments (Ziv and Smith, the impact of glutamate cycling may particularly
1996). Some of these larger filaments appear to persist apparent in more metabolically active parts of the
and take the form of dendritic spines (Goda and Davis, brain, such as the hippocampus.
2003). If stabilized these spines then become synapses The existence of high levels of glycogen stores
(Calabrese et al., 2006). Small filaments that do not (Pellegri et al., 1996) in the hippocampus is consistent
become large filaments presumably die off, forming with a high local energy flux. Furthermore, in humans,
an ongoing cycle of production, growth, and loss. there is a substantial literature demonstrating that
glucose ingestion improves performance on memory- hypoglycemia within local areas of the brain is a
dependent, but not other, cognitive tasks (Meikle et al., potential outcome of reduced glucose availability.
2004; Riby et al., 2006), a finding that is thought to Given the high demand for glucose throughout the
reflect the effects of glucose on hippocampal function. brain hypoglycemia could occur on a very short time
In terms of neuroplasticity, Segovia et al. (2006) scale. Thus the intensity of short-term activity of
report that environmental enrichment has an impact specific regions of the brain may be directly related to
on the hippocampus through elevated levels of glutam- local glycogen availability.
ate. In a sample of rats, environmental enrichment In the only human study to date, Oz et al., (2007)
promoted both neurogenesis and increased levels of report that total glycogen stores represent three to four
glutamate and GABA in the CA3 area of the hippocam- times the energy equivalents from glucose in brain
pus. While this finding is intriguing more research circulation, suggesting that in terms of normal func-
is needed to confirm a role for glutamate cycling in tion glycogen stores are in fact rather substantial, and
hippocampal function. may play a key role in brain metabolism. On the other
In addition to the hippocampus, the anterior hand, Oz et al. (2007) also report negligible consump-
cingulate cortex may also be particularly metabolically tion of glycogen from neurons in the visual cortex
active as part of its role in executive function (Posner during a 20 minute visual task, suggesting that glyco-
and Rothbart, 1998), the default brain network gen stores may not be important in the course of
(Margulies et al., 2007) and as a way station between normal brain activation and or function.
emotion and cognition (Allman et al., 2001). Even In contrast, animal models indicate that glycogen is
when the brain is not engaged in a focused task, the depleted under hypoglycemic conditions (Gruetter,
anterior cingulate cortex may be active in maintaining 2003; Brown, 2004). Furthermore, during brain acti-
generalized attention to both external and internal vation oxygen consumption does not initially increase,
signals. Recent work in humans has linked glutamate which has been taken to indicate that other sources of
levels in the anterior cingulate cortex and hippocam- energy, i.e., glycogen are being utilized rather than
pus to sensation-seeking (Gallinat et al., 2007), consist- direct oxidation of glucose (Raichle and Mintun,
ent with an important role for glutamate cycling in 2006). It is estimated that during brain activation in
these two brain structures. Again more research is the rat glycogen stores are depleted by about 15%,
needed to determine if glutamate cycling is associated suggesting that glycogen stores within astrocytes are
with higher glucose consumption in the anterior used to support the initial costs of brain activation
cingulate cortex. (Schurr et al., 1999; Shulman et al., 2001).
Furthermore, the more metabolically active parts
of the brain have higher levels of glycogen storage and
ENERGY STORAGE deplete those stores faster than less metabolically
active regions (Brown, 2004). For instance, mouse
It was once thought that the brain had practically no cerebral cortex has a higher glycogen content than do
energy storage leaving it critically and globally depend- deeper layers (Folbergrová et al., 1970) and the dentate
ent on an immediate supply of blood glucose. However, gyrus of the hippocampus, the only area with active
recent research has emphasized the existence of neurogenesis, has twice the glycogen content of the
glycogen stores throughout the brain (Gruetter 2003; rest of the hippocampus (Lipton, 1989). These findings
Brown, 2004). The primary storage of glycogen is in clearly suggest that glycogen stores act as an active
astrocytes (Phelps, 1972), though some may be stored buffer against glucose utilization during regional brain
in neurons (Brown, 2004). Glycogen stores in the brain metabolism.
had been previously overlooked largely because of their
low levels. At 0.1% of total brain weight (Brown, 2004)
Energy storage and sleep
they are much lower than those of other tissues, for
instance 20 times lower than that found in muscle Sleep, with its drastic behavioral inhibition, provides
(Oz et al., 2007). one way of considering the role of energy metabolism,
It is widely thought that glycogen stores are suffi- including that of glycogen, in brain function (Brown,
cient to support brain function for only a few minutes 2004). Among humans, overall brain energy consump-
(Clarke and Sokoloff, 1999). More recent work has tion as measured by oxygen uptake has been estimated
extended that estimate to 100 minutes (Gruetter, to a decrease by 3–11% during light sleep, and by
2003). This is rather surprising given the sensitivity of 25–44% during slow wave sleep, but very little during
the brain to hypoxia and suggests that ultimately the REM sleep (Madsen and Virstrup, 1991; Madsen et al.,
limiting factor in brain function is not energy but 1991). The lack of decline during REM sleep empha-
oxygen. Global brain oxygen depletion, however, sizes that the brain is in fact metabolically active,
is not a normal condition. On the other hand, rather than quiescent, during dreaming.
Detailed studies in rats suggest that glycogen the brain can not run on lactate by itself, the utilization
synthesis is dramatically increased during slow wave of lactate by neurons suggests that lactate can be sub-
sleep relative to waking (Karnovsky et al., 1983). stituted for glucose to sustain neurons in the short
Furthermore, sleep deprivation leads to a decrease in term. Such substitution is potentially important since
glycogen in the frontal cortex of rats (Djuricic et al., lactate is a by-product of other energy processes in the
1977; Kong et al., 2002; though see Gip et al., 2002). body.
This has lead to the suggestion that the function In fact, during vigorous exercise global brain
of sleep may be the replenishment of glycogen glucose uptake declines, while the uptake of lactate by
(Bennington and Heller, 1995). the brain increases, in inverse proportion (Kemppai-
More recent work demonstrating variation in nen et al., 2005). At the same time lactate levels in the
glycogen content in response to sleep deprivation in brain do not increase, suggesting utilization of lactate
different strains of mice have been taken to suggest in neurons (Dalsgaard et al., 2004). The brain appears
that accumulation of glycogen is not the primary func- to utilize lactate produced by somatic effort to directly
tion of sleep (Franken et al., 2003). However, to the fuel the metabolism of neurons, by-passing the conver-
extent that glycogen represents a short-term buffer sion of glucose or glycogen within astrocyctes. Further-
against increased energy demands of neuronal activity, more, glycogen stores increase during recovery from
interference with glycogen metabolism may be an exercise (Dalsgaard, 2006), leading to the conclusion
important intermediate in explaining the impact of that they are depleted with the onset of neural activity
sleep disruption on brain function (McEwen, 2006), associated with exercise, but not afterwards. Thus it
and ultimately the function of sleep. appears that during strenuous exercise, glucose may be
preferentially allocated to somatic energy uses over
those of the brain, which is forced to deplete glycogen
SUBSTRATE SPECIFICITY stores and utilize somatic metabolic wastes for its
energetic requirements.
As noted earlier, the brain was long considered to be Such reallocation of energy substrates may have
entirely dependent on glucose as a fuel. From an evolu- important implications human brain evolution. Based
tionary perspective, such dependence suggests that on anatomical features, humans have been argued to
glucose metabolism may have been an important have adopted endurance running as basic strategy for
limiting factor in the evolution of the large human hunting (Bramble and Lieberman, 2005; Lieberman
brain. While glucose can be produced from protein in and Bramble, 2007) and hence energy acquisition. If
the liver by the process of gluconeogenesis, the process so, running in the tropical heat would have placed
is rather slow and glucose is most easily derived from additional energy demands on both the brain and the
the consumption of carbohydrates. As has been argued body. Increased use of lactate from muscle would
for polyunsaturated fatty acids (PUFAs) (Broadhurst decrease the need for the immediate metabolism of
et al., 2002, though see Carlson and Kingston, 2007 glucose, increasing the duration of exercise possible
for an opposing perspective) or protein (Kennedy, without endangering brain function, and linking the
2005) the availability of carbohydrates could have been potential for increased brain size with the success of
an important constraint in the evolution of the human endurance running as part of a subsistence strategy.
brain. Thus consumption of underground storage
organs, with relatively high starch composition, might
have played a role in the evolution of the human brain BRAIN DEVELOPMENT
(Yeakel et al., 2007).
However, in addition to glucose, the brain can also In the first part of this paper I argued that the energet-
utilize ketones for fuel, and ketones have long been ics of the human brain could be seen as a trade-off
considered a back-up supply in the case of starvation between the constraints of energetic cost, demand,
when glucose is in short supply (Emery, 2005). While substrate specificity, and blood–brain barrier versus
peripheral fat produces fatty acids which can be util- the benefits of neuroplasticity. Such trade-offs will be
ized by muscle, ketones are produced from abdominal present at all times, but may be particularly evident
fat suggesting that the development of a substantial during conditions of high energy demand such as high
abdominal fat depot in human may be an important activity levels. Brain development is another, more
buffer for the human brain (Peters et al., 2004). This extended, period of elevated brain energy utilization.
may be particularly important in infants (Kuzawa, Thus the trade-off between energy and neuroplasticity
1998; Cunnane and Crawford, 2003). should be evident during the development of the
The discovery of the neuronal-lactate shuttle sug- human brain as well.
gests the possibility of a more finely tuned facultative At the broadest level, the overall energetic cost of
use of alternative substrates by the human brain. While brain development may be subsidized by additional
somatic energy stores or traded-off against somatic low from one to two months to two years (Lauriat
growth and development by temporally offsetting et al., 2007). Together reduced glucose availability
periods of elevated brain and somatic energy utiliza- and low levels of EAAT2 may leave the infant brain
tion. For instance, the high level of adiposity seen in particularly susceptible to glutamate excitoxicity, as
human infants has been argued to represent energy suggested by the relatively high rate of seizures during
stores put on in utero to support continued brain this period (Lauriat et al., 2007).
growth for the first year postnatally (Kuzawa, 1998; During infancy it is thought that experience plays
Cunnane and Crawford, 2003). Similarly, very slow a key role in the development of fundamental emotional
growth during human childhood (Bogin, 1999) may circuits in the brain. Alan Schore (1994, 1997, 2002) has
be a reduction of somatic energy costs in favor of suggested that negative affect associated with trauma
brain development and neuroplasticity during a period and neglect during the first two years of life results in a
of high brain metabolism from 4 to 10 years of age hypermetabolic state of arousal, including elevated
(Chugani, 1998). cortisol levels and the activation of the sympathetic
In addition to overall energy consumption, the nervous system. Schore suggests that if sufficiently
specific substrates which the brain uses to meet its prolonged, such arousal may lead to elevated levels of
energy requirements change during development. For glutamate and resulting excitoxicity, particularly in
instance, despite the importance of glucose to brain the orbitofrontal cortex, anterior cingulate cortex,
function, it is well known that infants utilize ketones and amygdale, which are developing during this period.
and lactate as fuel, thus potentially sparing glucose for Glutamate exotoxic shaping of emotional circuits
other functions (Nehlig, 2004). However, the capacity appears to reflect a close association of nutrition and
of the brain to metabolize ketones declines as the child emotional conditions during infancy. Schore’s argu-
grows, leading to an increasing demand for glucose. In ment is focused early childhood trauma and neglect
what follows we consider brain development and its and its effects on the development of psychopathology.
implications for the allocation of energy to the brain But such an argument is applicable to infant brain
and body starting with infancy. development under conditions of nutritional as well
as emotional stress. Given the potentially low levels of
glucose availability during infancy, as well as the risk
Infant brain development
of infectious disease in traditional societies, many
Brain metabolism is estimated to represent some infants may exist in a state of metabolic brain arousal,
50–80% of the energy budget of the human infant leading to glutamate excitoxicity during periods of
(Holliday, 1986). This reflects the large size of the acute undernutrition. In support of this, acute under-
brain relative to the body, as well as rapid brain nutrition during infancy has been associated with cere-
growth during the first two years of life (Leigh, bral atrophy (Hazin et al., 2007) and disruption of
2004), a period of extensive synaptogenesis and high dendrite development (Benitez-Bribiesca et al., 1999).
levels of synaptic density, as well as the myelinization Thus it has been suggested that the rather remark-
of major nerve tracts (Carmondy et al., 2004). In add- able degree of adiposity exhibited by human infants
ition, the hippocampus and amgydala are developing may represent a metabolic buffer for brain develop-
during this period. ment (Kuzawa, 1998; Cunnane and Crawford, 2003).
It is important to note that breast milk, the primary Adipose tissue itself can not be metabolized by the
food in early infancy is rich in lipids, but a relatively brain. However, the visceral component of adiposity
poor source of glucose. However, lactate and ketone can be metabolized to produce ketones for the brain,
bodies, not glucose appear to be important energy sub- which are an important source of energy and myleni-
strates for the brain during this period (Edmond, 1992; zation for the infant brain as outlined above. On the
Nehlig, 2004; Medina and Tabernero, 2005). In particu- other hand, subcutaneous fat stores may be used to
lar, ketones can be used by oligodendryctes to make support the energetic requirements of the immune
the lipids that are part of myelin, sparing glucose for system during infancy, which would free up glucose
other pathways (Nehlig 2004). In addition, ketones to be used by the brain (Kuzawa, 1998).
appear to shunt glutamine toward the production of
GABA rather than glutamate (Melø et al., 2006), thus
Childhood brain development
potentially reducing the risk of glutamate excitoxicity.
In fact, glucose may be in relatively short supply in Important changes in human brain metabolism are
the infant brain. Glucose utilization rates during evident around the age of three to four years, when
infancy start relatively low, reaching adult levels by glucose utilization rates reach their peak, at about
around the age of two years (Chugani, 1998). Further- twice the level observed in adults (Chugani, 1998).
more, levels of EAAT2, the transporter that removes The executive attention system, which integrates atten-
glutamate from the synapse to astrocytes are relatively tion and executive function, is undergoing rapid
development between three and seven years of age In fact, the energetic demands of brain develop-
(Posner, 2005), including the development of the thal- ment may be quite a bit higher than usually calculated,
amus, the parietal lobe, the orbitofrontal cortex, and since they include the costs of physical activity critical
the anterior cingulate cortex. Thus the early increase in to brain development as well as the metabolic costs of
glucose utilization may be directly related to the brain tissue. For instance, it has been calculated that
growth and development to these parts of the brain. 17% of the total energy budget for children six years of
Glucose utilization rates, however, remain elevated age is consumed by physical activity (Dufour, 1997).
until around the age of 11 when they begin to decline to Much of the physical activity during childhood clearly
adult rates (Chugani, 1998). Brain growth is 95% com- serves multiple purposes and can not be attributed
plete by the age of 7 (Caviness et al., 1996), suggesting solely to a specific function. However, the costs of
that the high rate of glucose utilization after the age of physical activity, which helps shape brain development
7 is not a function of increasing brain size. Instead, the and promotes learning through the release of brain-
high glucose demand of the brain during this period is derived neurotrophic factor (BDNF) (Winter et al.,
presumably related to enhanced synaptic plasticity 2007), must be taken into account in calculating the
(Chugani, 1998), which I have argued is maintained full energetic cost of brain development.
by the energetic costs of glutamate cycling.
In fact, the juvenile period is associated with
Adolescence
synaptic pruning, i.e., the loss of established neuronal
connections, a process known to continue in adoles- Compared to childhood, during which elevated glucose
cence (Huttenlocker, 1984; Huttenlocker and Dab- utilization rates suggest a dynamic process of synaptic
holkar, 1997). Such pruning is based on experience; formation and pruning, adolescence is thought to be
neuronal connections that are used are strengthened associated with the pruning of synaptic connections
and those that are not are lost. Recent studies indicat- (Huttenlocker and Dabholkar, 1997, Gogtay et al.,
ing cortical maturation associated with declines in 2004). If I am correct, such synaptic pruning is associ-
gray matter starting around the age of six (Gogtay ated with reduction of glucose-fueled glutamate
et al., 2004) are consistent with the decreased number cycling and reflected in declining rates of cerebral glu-
of synaptic connections during this period. cose utilization throughout the brain. In fact, there
Thus, the age pattern of glucose utilization rates is does appear to a loss of generalized neuroplasticity,
suggestive of an important shift in brain function as indicated by declining language acquisition ability,
during childhood linking social context, nutrition, around the age of 12 (Sakai, 2005), roughly the same
and behavior. The onset of peak levels at three to four time that that glucose utilization rates start to decline.
years of age is roughly coincident with the natural end However, localized synaptic plasticity may be main-
of lactation (Martin, 2007). Weaning represents a tained, particularly in the prefrontal cortex, still matur-
switch away from breast milk to other sources of food ing through out adolescence (Sowell et al., 1999;
that are generally higher in carbohydrate content and Gogtay et al., 2004).
may provide a greater source of glucose for the brain. In addition to declining brain plasticity, the puber-
In addition, weaning marks a change in the child’s tal drop in glucose utilization by the brain appears to
social environment as well, as children start to spend reflect an increased allocation of energy to somatic
increasing time in play with sibling and other children, growth associated with the pubertal growth spurt. The
and less time in such close proximity with their onset of puberty has been linked to abdominal fat stores
mother. In other words, children between the ages of in both boys and girls (Vizmanos and Marti-Henneberg,
approximately 4–11 years of age soak up an increasing 2000), the same fat stores that are thought to serve as a
variety of environmental influences, all of which may reserve source of ketones for the brain (Peters et al.,
promote the development of synaptic connections 2004), potentially placing reproductive maturation
with relatively little additional reinforcement. and brain development in direct energetic competition.
The period from 4–11 years of age, roughly the Boys appear to utilize prepubertal adipose storage
period between weaning and puberty, is also a period as the basis for increased size and muscularity in asso-
of very slow and decreasing somatic growth (Bogin, ciation with increased testosterone production (Camp-
1999). It has been argued that somatic growth is sup- bell and Mbzivo, 2006). Behaviorally these changes are
pressed during this stage to allow for the increased presumably associated with male–male competition
energetic costs of growing a large brain. However, for mates (Hilton et al., 2000). For girls, puberty is
given that growth in brain volume is almost entirely associated with increased estrogen production and
completed by the age of seven, it seems more accurate the deposition of fat stores that play an important role
to say that the slow rate of somatic growth during in the modulation of reproductive function, including
the juvenile period represents a priority in the use of ovarian cycling, and potential pregnancy and lactation
glucose for brain development over somatic growth. (Ellison, 2001).
The same gonadal steroids that promote second- (see Campbell et al., 2005, for an example). Thus in
ary sexual characteristics and fuel somatic growth the natural human life course, rather than being a
also act on the brain to change behavior during distinct postpubertal period, young adulthood may
adolescence (Sisk and Zehr, 2005). The continued represent a final stage of development in which repro-
maturation of the prefrontal cortex involves the ductive, somatic, and brain maturation all converge to
experience-dependent maturation of the cortico- produce a fully functioning reproductive adult.
thalamic-striatal circuit (Chambers et al., 2003; Crews
et al., 2007). Testosterone may play a role in this
process by modulating the dopaminergic reward SUMMARY
system (Wood, 2004; Frye, 2007) while estrogen may
have a role through its effects on the serotonergic Recent advances in neuroscience and brain imaging
system (Lasiuk and Hegadoren, 2007), thus linking have greatly enlarged our understanding of human
reproductive hormones and the reinforcement of brain metabolism and made the brain much more
behavioral predispositions. amenable to an energetic and evolutionary analysis.
From an energetic point of view, the timing of In addition to the well-known overall energetic cost of
hormonal changes and their behavioral consequences the brain and its dependence on glucose as a substrate,
during adolescence is a function of energy availability. more recent work has emphasized the fact that brain is
Greater energy availability promotes faster childhood energetically demanding and in a position to regulate
growth with earlier pubertal onset, including reproduct- its own energy supply. The human brain is also highly
ive hormones (Ellison, 2001). Reproductive hormones plastic, and can utilize more than one substrate, both
promote secondary characteristics which attract the during development and adulthood. It is this plasticity
attention of others (see Waylen and Wolke, 2004, for (in addition to the large size) that gives the human
a recent review), while at the same time acting on the brain its amazing flexibility and may play a central
developing circuits in the brain to organize behavior, role in the cognitive powers that we hold so crucial
including libido (Sisk and Foster 2004; Sisk and Zehr, to the nature of our species.
2005). Thus earlier maturers not only stand out phys- I argue that much of the energetic cost of the human
ically from their peers, but their brains are being brain can be linked to the use of glucose in glutamate
shaped by the experience of being more advanced sexu- cycling and its role in maintaining synaptic plasticity.
ally than their peers, which may reinforce sexual Glutamate cycling involves the neuron-lactate-astrocyte
behavior during adulthood as well as well (Ostovich shuttle, an on-going process, which may underlie intrin-
and Sabini, 2005). sic brain activity, thus accounting for the energetically
expensive and demanding properties of the human
brain. Furthermore, though glucose remains the pre-
Young adulthood
ferred fuel for brain activity, the capacity of neurons
Even after puberty is complete, and the production of to metabolism lactate and ketones appears to provide
reproductive hormones has leveled off, the brain con- additional mechanisms for trade-offs between brain
tinues to develop finishing with the maturation of the and somatic energy utilization. Such mechanisms are
prefrontal cortex some time in the early 20s (Gogtay important in physical exercise and may have provided a
et al., 2004). Glucose utilization rates in the anterior means to circumvent energetic constraints on physical
cingulate cortex, a central structure in monitoring activity associated with subsistence strategies under-
emotional impulses from the amygdala (Pezawas writing the evolution of a large human brain.
et al., 2005; Etkin et al. 2006) have been shown to Developmentally, changes in the energetic costs of
increase until the middle of the 20s (Van Bogaert the brain appear to map onto important neurological
et al., 1998). The anterior cingulate cortex appears and behavioral stages of human development. The
particularly affected by the adrenal hormone dehy- infant brain appears to be buffered from the effects of
droepiandrosterone (DHEA) (Alhaj et al., 2006), which potential low energy availability during its rapid
continues to increase into the 20s as well (Orentreich growth by a store of adipose tissue. On the other hand,
et al., 1984; Sulcova et al., 1997). Together, these find- elevated brain glucose utilization between the ages of
ings suggest a young-adult period characterized by 4 and 11 years appears to coincide with the onset of
continued brain maturation in the absence of further adrenarche, suggesting that the neuroprotective effects
somatic and reproductive maturation. of dehydroepiandrosterone sulfate (DHEAS) may be
However, such a characterization may be mislead- important in maintaining synaptic plasticity, thus pro-
ing given that favorable energetic conditions in indus- moting learning and socialization in prepubescent
trialized populations has lead to early reproductive children.
maturation. In many societies with low food availa- During adolescence the timing of puberty and
bility somatic growth continues into the early 20s the rise of reproductive hormones reflects energy
availability. Thus those who physically mature early two years, including Peter Ellison, Dan Eisenberg,
will not only show earlier brain maturation, but such Peter Gray, and the Tea and Hormones group.
maturation will tend to develop in social circumstances I would also like to thank Robert Campbell for his
favoring sexual behavior and thus shape their brain continued encouragement to purse this topic. All errors
to expect similar circumstances during adulthood. are my own.
Though it appears that this integrative developmental
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26 Embodied Capital and Extra-somatic
Wealth in Human Evolution
and Human History
Jane B. Lancaster and Hillard S. Kaplan
INTRODUCTION capital in the form of skills, education, and training. In

past civilizations, going back to Babylonia in the third
This chapter presents a theory of brain and life span millennia BC, literacy and numeracy were known but
evolution and applies it to both primates in general, exceedingly rare skills. This pattern continued world-
and to the hominid line, in particular. To address the wide until 1800 in Western Europe, including England,
simultaneous effects of natural selection on the brain where these skills went from rarity to the norm in
and on the life span, it extends the standard life history under a century (Clark, 2007). Labor markets with a
theory in biology which organizes research into the particular demand for embodied capital in their
evolutionary forces shaping age-schedules of fertility workers place new demands on human life history
and mortality. This extension, the embodied capital and reproductive strategies in terms of mate choice,
theory, integrates existing models with an economic fertility, investment in children, and the timing of
analysis of capital investments and the value of life. reproduction in the life course. Once again, human life
The chapter begins with a brief introduction to history radically changed in shape to a new emphasis
embodied capital theory, and then applies it to under- on the acquisition of skills through training and educa-
standing major trends in primate evolution and the spe- tion, postponement of reproduction to the late 20s,
cific characteristics of humans. The evolution of brain and radically reduced completed family size with the
size, intelligence, and life histories in the primate order reproductive part of the life course compressed into
are addressed first. The evolution of the human life less than a decade.
course is then considered, with a specific focus on the
relationship between cognitive development, economic
productivity, and longevity. It will be argued that the EMBODIED CAPITAL AND THE COEVOLUTION
evolution of the human brain entailed a series of coevolu- OF INTELLIGENCE, DIET, AND LONGEVITY
tionary responses in human development and aging.
The second section on embodied capital and extra- According to the theory of evolution by natural selection,
somatic wealth discusses humans in a comparative organic evolution is the result of a process in which
context, beginning with the hunting and gathering variant forms compete to harvest energy from the envir-
lifestyle because of its relevance to the vast majority onment and convert that energy into replicates of those
of human evolutionary history. However, in the past forms. Forms that can capture more energy and convert
10 000 years human history traced a series of beha- that energy more efficiently into replicates of themselves
vioral adaptations based on ecology and individual become more prevalent through time. This simple issue
condition. The introduction of extra-somatic capital, of harvesting energy and converting energy into off-
first in the form of livestock and later in land and spring generates many complex problems that are
other types of wealth and power, radically changed time-dependent (Gadgil and Bossert, 1970).
the shape of human life history parameters and pro- Two fundamental trade-offs determine the action
duced new patterns of fertility, parental investment, of natural selection on life history strategies. The first
and reproductive regimes as access to extra-somatic trade-off is between current and future reproduction.
capital became a focus of life history strategies. By growing, an organism can increase its energy
Finally, modern skills-based, competitive labor capture capacities in the future and thus increase its
markets, combined with reduced fertility during the future fertility. For this reason, organisms typically
nineteenth century, mark a returning focus on embodied have a juvenile phase in which fertility is zero until
439
440 Jane B. Lancaster and Hillard S. Kaplan
they reach a size at which some allocation to reproduc- expansion among higher primates, along with enhanced
tion increases lifetime fitness more than does growth. learning abilities, reflects increased investment in trans-
Similarly, among organisms that engage in repeated forming present experience into future performance
bouts of reproduction (humans included), some energy (Armstrong and Falk, 1982; Fleagle, 1999).
during the reproductive phase is diverted away from The action of natural selection on neural tissue
reproduction and allocated to maintenance so that involved in learning and memory should depend on
they can live to reproduce again. Natural selection is costs and benefits realized over the organism’s lifetime.
expected to optimize the allocation of energy to current Three kinds of costs are likely to be of particular
reproduction and to future reproduction (via invest- importance. Firstly, there are the initial energetic costs
ments in growth and maintenance) at each point in of growing the brain. Among mammals, those costs
the life course so that genetic descendents are maxi- are largely born by the mother during pregnancy and
mized (Gadgil and Bossert, 1970). Variation across lactation. Secondly, there are the energetic costs of
taxa and across conditions in optimal energy allo- maintaining neural tissue. Among infant humans,
cations is shaped by ecological factors, such as food about 65% of all resting energetic expenditure supports
supply, disease, access to mates, and predation rates. maintenance and growth of the brain (Holliday, 1978).
A second fundamental life history trade-off is Thirdly, certain brain abilities may actually decrease
between offspring number (quantity) and offspring performance early in life. Specifically, the capacity to
fitness (quality). This trade-off occurs because parents learn and increased behavioral flexibility may entail
have limited resources to invest in offspring and each reductions in “preprogrammed” behavioral routines.
additional offspring produced necessarily reduces ave- The incompetence with which human infants and
rage investment per offspring. Most biological models children perform many motor tasks is an example.
operationalize this trade-off as number versus survival Some allocations to investments in brain tissue may
of offspring (Lack, 1954; Smith and Fretwell, 1974; Lloyd, provide immediate benefits (e.g., perceptual abilities,
1987). However, parental investment may not only affect motor co-ordination). Other benefits of brain tissue
survival to adulthood, but also the adult productivity and are only realized as the organism ages. The acquisition
fertility of offspring. This is especially true of humans. of knowledge and skills has benefits that, at least in
Thus, natural selection is expected to shape investment part, depend on their impact on future productivity.
per offspring and offspring number so as to maximize Consider two alternative cases, using as an example,
offspring number times their average lifetime fitness. the difficulty and learning-intensiveness of the orga-
The embodied capital theory generalizes existing nism’s foraging niche. In the easy-feeding niche where
life history theory by treating the processes of growth, there is little to learn and information to process, net
development, and maintenance as investments in productivity (excess energy above and beyond mainte-
stocks of somatic, or embodied, capital. In a physical nance costs of brain and body) reaches its asymptote
sense, embodied capital is organized somatic tissue – early in life. There is a relatively small impact of the
muscles, digestive organs, immune competence, brains, brain on productivity late in life (because there has been
etc. In a functional sense, embodied capital includes little to learn), but there are higher costs of the brain
strength, speed, immune function, skill, knowledge, early in life. Unless the life span is exceptionally long,
and other qualities such as social networks and status. natural selection will favor the smaller brain.
Since such stocks tend to depreciate with time, alloca- In the difficult-feeding niche, the large-brain crea-
tions to maintenance can also be seen as investments ture is slightly worse off than the small-brain one early
in embodied capital. Thus, the present-future repro- in life (because the brain is costly and learning is taking
ductive trade-off can be understood in terms of optimal place), but much better off later in life. The effect of
investments in own embodied capital versus reproduc- natural selection will depend upon the probabilities
tion, and the quantity–quality trade-off can be under- of reaching the older ages. If those probabilities are
stood in terms of investments in the embodied capital sufficiently low, the small brain will be favored, and if
of offspring versus their number. they are sufficiently high, the large brain will be
favored. Thus, selection on learning-based neural capi-
tal depends not only on its immediate costs and
The brain as embodied capital
benefits, but also upon mortality schedules which
The brain is a special form of embodied capital. Neural affect the expected gains in the future.
tissue is involved in monitoring the organism’s internal
and external environments and organizing physio-
The human adaptive complex
logical and behavioral adjustments to those stimuli
(Jerison, 1976). Portions (particularly the cerebral The human adaptive complex is a coadapted complex
cortex) are also involved in transforming past and of traits, including: (1) the life history of development,
present experience into future performance. Cortical aging and longevity; (2) diet and dietary physiology;
Embodied Capital and Extra-somatic Wealth in Human Evolution and Human History 441
(3) energetics of reproduction; (4) social relationships TABLE 26.1. Life history characteristics and diet of
among men and women; (5) intergenerational resource human foragers and chimpanzees (after Lancaster and
transfers; and (6) co-operation among related and Kaplan, 2008).
unrelated individuals (Kaplan, 1997; Kaplan et al.,
Life history
2000, 2001, 2003, 2005, 2007; Kaplan and Robson, characteristics Human foragers Chimpanzees
2002; Robson and Kaplan, 2003; Gurven and Kaplan,
2006; Gurven and Walker, 2006). It describes a very Maximum life ~100 ~60
span
specialized niche, characterized by: (1) the highest-
Probability of 0.6 0.35
quality, most nutrient-dense, largest package size, food
survival to
resources from both plants and animals; (2) learning- age 15
intensive, sometimes technology-intensive, and often Expected age 54.1 29.7
co-operative, food acquisition techniques; (3) a large of death at
brain to learn and store a great deal of context-dependent 15 (years)
environmental information and to develop creative Mean age first 19.7 14.3
food acquisition techniques; (4) a long period of reproduction
(years)
juvenile dependence to support brain development
and learning; (5) low juvenile and even lower adult Mean age last 39 27.7**
reproduction
mortality rates, generating a long productive life span (years)
and a population age structure with a high ratio of
Interbirth 41.3 66.7
adult producers to juvenile dependents; (6) a three- interval*
generational system of downward resource flows from (months)
grandparents to parents, to children; (7) biparental Mean weight at 15.7 10
investment with men specializing in energetic support age 5 (kg)
and women combining energetic support with direct Mean weight at 24.9 22.5
care of children; (8) marriage and long-term reproduc- age 10 (kg)
tive unions; (9) co-operative arrangements among kin
Composition
and unrelated individuals to reduce variance in food of diet (%)
availability through sharing and to more effectively
Collected 9 4
acquire resources in group pursuits.
The publications cited above show that the majority Extracted 31 4
of the foods consumed by contemporary hunter- Hunted 60 2
gatherers worldwide are calorically dense, hunted, Contributions
and extracted (taken from an embedded or protected by sex (%) Men Women
matrix – underground, in shells, etc.) resources,
Adult calories 68 32 Sexes
accounting for 60% and 35% of calories, respectively. independent
Adult Protein 88 12
Extractive foraging and hunting proficiency generally
Caloric support 97 3
does not peak until the mid-30s, because they are
for offspring
learning – and technique – intensive. Hunting, in par-
Protein support 100 0
ticular, demands great skill and knowledge that takes for offspring
years to learn, with the amount of meat acquired per
unit time more than doubling from age 20 to age 40, Notes: *Mean interbirth interval following a surviving infant.
**Age of last reproduction for chimpanzee females was
even though strength peaks in the early 20s. This learn- estimated as two years prior to the mean adult life expectancy.
ing-intensive foraging niche generates large calorie
deficits until age 20, and great calorie surpluses later
in life. This life history profile of hunter-gatherer
productivity is only economically viable with a long relative in phylogenetic terms. Table 26.1 presents
expected adult life span. major differences in five critical parameters of life
history: (1) survivorship to age of first reproduction;
(2) life expectancy at the beginning of the reproductive
LIFE HISTORIES OF WILD CHIMPANZEES period; (3) absolute and relative length of the postre-
AND HUMAN FORAGERS productive period; (4) spacing between births of sur-
viving offspring; and (5) growth during the juvenile
To appreciate the implications of the human adaptive period (Kaplan et al., 2000; Lancaster et al., 2000).
complex for the life histories of foragers, it is useful to The data for these analyses are based on published
compare humans with the chimpanzee, another large- data sets on the only four forager groups for which full
bodied, long-lived mammal, and our closest-living demographic data are available as well as food
consumption and production throughout the year for CONSUMPTION AND PRODUCTIVITY
all age and sex categories (Aché, Hadza, Hiwi, and THROUGH THE LIFE COURSE
!Kung). The data on chimpanzees are based on studies
at the African field sites of Bossou, Gombe, Kibale, Table 26.1 also demonstrates the overlap in component
Mahale, and Tai. The data and full citation list are categories of the diets of foraging societies and chi-
presented in Kaplan et al. (2000, Table 1, p. 158). mpanzee communities as well as wide differences in
Human and chimpanzee life history parameters relative proportions (Kaplan et al., 2000; Lancaster
based on data from these extant groups of hunter- et al., 2000). For example, hunted meat makes up
gatherers and wild chimpanzees indicate that forager about 2% of chimpanzee but 60% of forager diets.
children experience higher survival to age 15 (60% vs. Chimpanzees rely on collected foods for 94% of their
35%) and higher growth rates during the first 5 years nutrition, especially ripe fruits. Such foods are nutri-
of life (2.6 kg/year vs. 1.6 kg/year). Chimpanzees, how- tious and are neither hard to harvest nor learning
ever, grow faster both in absolute and proportional intensive, at least relative to human resource pursuits.
weight gain between the ages of 5–10 years. The early Humans depend on extracted or hunted foods for 91%
high-weight gain in humans may be the result of the of their diet. The data suggest that humans specialize
earlier weaning age (2.5 years vs. 5 years) followed by in rare but nutrient dense resources (meat, roots, nuts)
provisioning of highly processed and nutritious foods, whereas chimpanzees specialize in ripe fruit and
foods that juvenile chimpanzees could never collect to fibrous plant parts. These fundamental differences in
any extent. Fast growth and weight gain during infancy diet are reflected in gut morphology and food passage
and the early juvenile period may also represent an times in which chimpanzees experience rapid passage
adaptation to support the energetic demands of brain of bulky, fibrous meals processed in the large intestine
growth development, since a significant portion of this whereas human process nutritionally dense, lower
weight gain is in the form of fat. volume meals amenable to slow digestion in the small
The chimpanzee juvenile period is shorter than that intestine (Milton and Demment, 1988).
for humans with age at first birth by chimpanzee Table 26.1 also summarizes the relative contribu-
females about five years earlier than among forager tions of both sexes to the nutritional support of group
women. This is followed by a dramatically shorter members through food sharing, one of the critical
adult life span for chimpanzees. At age 15, chimpanzee features of the human adaptive pattern. This table is
life expectancy is an additional 15 years, whereas for- based on contributions by sex in 10 modern forager
agers can expect to live an additional 38 years having societies (Onge, Anbarra, Arnhm, Aché, Nukak, Hiwi,
survived to age 15. Importantly, women spend more !Kung (2), Gwi and Hadza) where daily adult caloric
than a third of their adult lives in a postreproductive production of meat, roots, fruits, and other has been
phase, whereas few chimpanzee females spend any documented (Kaplan et al., 2000, Table 2, p. 162).
time as postreproductives. The differences in overall Generally, women produce virtually no animal protein
survival probabilities and life span of the two species and the carbohydrate calories they produce help to
are striking: less than 10% of chimpanzees ever born support themselves and male hunters. As described in
survive to age 40 and virtually none survive past 50, the next paragraph, calories and protein consumed
whereas 45% of foragers reach 40 and more than 15% by children mostly comes from the large surpluses
of foragers born survive to age 70! supplied by adult males.
Finally, despite the fact that human juvenile and Figure 26.1 presents survivorship and net food pro-
adolescent periods take longer and that human infants duction through the life course of humans and chim-
are larger than chimpanzee at birth, forager women panzees (Kaplan et al., 2000). Humans consume more
are characterized by higher fertility. The mean inter- than they produce for the first third of their life course.
birth interval between offspring, when the first sur- In contrast chimpanzees are self-supporting by the age
vives to the birth of the second, is 1.6 times longer of five. Thus, human juveniles, unlike chimpanzee
among wild chimpanzees than among modern forager juveniles, have an evolutionary history of dependency
populations. on adults to provide their daily energy needs. Even
To summarize, human foragers show a juvenile more striking is the steady increase in productivity
period 1.4 times longer and a mean adult life span over consumption among humans into their 30s and
2.5 times longer than chimpanzees. They experience early 40s. Forager males begin to produce more than
higher survival at all ages postweaning, but slower they consume in their late teens, but their peak prod-
growth rates during mid childhood. Despite a long uctivity builds slowly from their early 20s until their
juvenile period, slower growth, an equal length repro- mid-to-late 30s and then is sustained for 20 or more
ductive period, and a long postreproductive life span, years at a level of approximately 6500 kcals per day.
forager women achieve higher fertility than do In contrast forager women vary greatly from group
chimpanzees. to group in energy production, depending upon the
1 Human survival 2000

Chimpanzee survival
1750
Net prod. humans
0.9
Net prod. chimps 1500
1250
0.8
1000
0.7 750
500
0.6
Net production
250
Survival
0.5 0
–250
0.4
–500
0.3 –750
–1000
0.2 –1250
–1500
0.1
–1750
0 –2000
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75
Age
26.1. Survivorship and net food production through the life course of humans and chimpanzees.
After Kaplan and Lancaster (2003).
demands of intensive childcare (Hurtado and Hill, EMBODIED CAPITAL AND EXTRA-SOMATIC
1990). In some groups, they consume more than they WEALTH IN THE PAST 10 000 YEARS
produce until sometime after menopause, when they
are finally freed from childcare demands; whereas in For most of human history from perhaps 2 million
others, such as the Aché, they remain nutritionally years until 10 000 years ago, humans depended on
dependent on men throughout their lives. The provi- investments embodied in their brains and bodies to
sioning of reproductive women and children has a survive and reproduce. They invested in themselves
powerful effect on the production of children by and their offspring through patterns of behavior that
humans by reducing the energy cost and health risk emphasized accessing high energy, hard to acquire
of lactation to the mother and by lifting the burden of foods that demanded skilled, learned performances,
self-feeding from the juvenile, thus permitting a food sharing, the feeding of juveniles, and a comple-
shortened interbirth interval without an increase in mentary division of labor between men and women.
maternal or juvenile mortality (Hawkes et al., 1998). However, about 10 000 years ago at the end of the last
The human adaptive complex is both broad and flex- Ice Age, the distribution of resources that humans
ible, in one sense, and very narrow and specialized in depended on and the means to access them began to
another. It is broad in the sense that as foragers, humans change as a result of climate change and an increase
have existed successfully in virtually all of the Earth’s in population density. At the beginning these changes
major habitats. It is narrow and specialized in that it is had little effect except to promote population growth.
based on a diet composed of nutrient-dense, difficult- Later their effects were so profound that patterns of
to-acquire foods and a life history with a long, slow devel- marriage, investment in children, and social organiza-
opment, a heavy commitment to learning and intelligence, tion appeared to reinvent themselves.
and an age-profile of production shifted towards older In the following sections we will evaluate the
ages. In order to achieve this diet, humans are very impact that changes in subsistence base and social
unproductive as children, have very costly brains, are organization made on the division of labor, family
extremely productive as adults, and engage in extensive formation strategies, fertility, and investment in
food sharing both within and among age- and sex-classes. children in response to sedentism, horticulture, the
domestication of large animals, agriculture, extra- example, female gardening of high-protein crops on
somatic wealth, social stratification, archaic despotic riverine alluvial soils, such as millet and sorghum in
states, inheritance, and modern skills-based labor much of village Africa (Colson, 1960; Lancaster, 1981),
markets and political systems. These hypotheses are is very different from subsistence based on manioc in
generalizations informed by the archaeological, his- the thin, lateritic soils of South America. There, male
toric, and cross-cultural record of today and the recent hunting is critical to balanced macronutrients in the
past and must remain as our best guesses as to the diet and frequent clearing of new fields is necessary.
temporal and causal relations involved. The critical need for defense of the village resource
base is supplied by males as an umbrella benefit rather
than to specific wives. However, since neither males
Sedentism and tribal horticulture
nor females produce beyond subsistence needs and
Village sedentism and the domestication of plants had the means of production are held in common through
a profound, yet limited, impact on human socioeco- usufruct, there is little opportunity for major differ-
logy. Subsistence based on horticulture rests on land- ences in quality to develop between males beyond their
extensive, slash-and-burn practices on prime resource embodied capital (age, health, hunting skill). However,
patches, access to which is maintained by the social variance in male reproductive success does arise on
group and defended by males against outsiders. (Land the basis of success in intergroup raiding that brings
intensive horticulture is later in time and very differ- certain male warriors numerous captive wives. How-
ent, being more like agriculture because it is based on ever, this advantage was much reduced under colonial
long-term improvements such as irrigation in which suppression of tribal warfare and raiding.
fields are heritable and represent wealth.) Within Reproduction in land-extensive, horticultural soci-
the group, access is on the basis of usufruct, a system eties is associated with near universal marriage for
of land tenure that gives all group members direct both sexes with reproduction beginning at sexual
rights to the means of production and reproduction maturity for women and extending through the entire
(Boserup, 1970; Goody, 1976). People live in small period of fecundity. Reproduction for men is some-
villages, larger than hunter-gatherer bands but simi- what delayed due to the need to access wives through
larly scaled in terms of face-to-face, kinship-laden either bride service (local group) or bride capture
interactions. (outside group); the first being a personal cost in labor
There is evidence that sedentism brought a reduc- contributed to the bride’s family and the second a cost
tion in child mortality compared to hunter-gatherers, in risk. However, the possibility of polygyny extends
as well as higher female fertility, although it is unclear the male reproductive period as new and younger
whether the strongest effects are in reduced birth wives can be added through time.
spacing or in higher rates of child survival. Bentley The high frequency of polygynous husbands asso-
et al. ((2001)), in comparing the fertility changes associated with horticulture is likely because each wife is
ciated with the prehistoric transition to agriculture essentially able to support herself and her children
report that, when comparing subsistence modes and through her own labor (Murdock, 1967; Lancaster
fertility rates, forager, horticultural, and pastoral and Kaplan, 1992). Males do not have to ponder
groups had similar fertility rates whereas increases whether they can afford additional wives and children,
were strongly associated with a higher dependence only how they to get and keep them. As White and
on agriculture. The potential of deaths from chronic Burton (1988) found, polygyny is most associated with
intergroup warfare and raiding increased. Using the fraternal interest groups, warfare for the capture of
archaeological and historic record, Keeley (1996) women, absence of constraints on expansion into new
found that for males the percentage mobilized in war lands and, especially for horticulturalists, environmen-
often reached 35–40% and male deaths ranged from tal quality and homogeneity. The frequent practice of
10 to nearly 60%. widow inheritance by husband’s kin also increases
Among contemporary horticulturalists, comple- the frequency of polygyny (Kirwin, 1979). Sororal
mentarity in the male and female division of labor is polygyny (the marriage of sisters) is at its highest
complex because of its link to local ecology. Garden frequency among horticulturalists perhaps due to the
production by women using the digging stick and hoe ease of closely related women forming collaborative,
provides the carbohydrate and caloric base of the diet horticultural work groups and child care (White and
and is easily combined with childcare (Boserup, 1970; Burton, 1988).
Goody, 1976). Males contribute their labor in clearing Parental investment in horticultural societies
fields, in animal protein through hunting and fishing, focuses on raising healthy children without concern
and in protection of the village resource base through for their marriage market endowments of extra-somatic
defense. The relative contribution, type, and impera- wealth or inheritance of resources. Birth into a social
tive of male help varies by ecological context. For group provides all the inheritance a child needs to
access the means of production and reproduction. wealth in large stock in such a readily divisible and
Such concepts as bastardy or disinheritance do not moveable form (as opposed to agricultural land) puts
play a formal role in family dynamics. Child labor is a high premium on males as defenders and raiders.
valuable to families since horticulture provides We find the warrior complex full-blown, with chronic
a number of relatively low-skilled tasks that older internal warfare, blood feuds, social segregation of a
children can perform (Bock, 2002b). In fact Kramer male warrior age class, fraternal interest groups, a
(2005b) demonstrated that among Maya horticultura- geographic flow of women from subordinate to domi-
lists older children contribute at the level of “helpers- nant groups through bride capture, and expansionist,
at-the-nest,” significantly increasing their parents’ segmentary lineages based on the male line (Sahlins,
fertility and without whose help their parents could 1961; DiVale and Harris, 1976; White and Burton,
not add additional offspring to the family. 1988; Low, 2000). Men with strong social alliances are
Variance in reproductive success is relatively low more likely to find at least some of their wives from
for women because marriage is universal, and female within their own social groups, whereas men from
fertility and fecundity depend on their own health, small or subordinate lineages are less likely to be
productivity, and work effort (Prentice and Whitehead, offered brides and are willing to take more risks in lieu
1987; Jasienska, 2000; Ellison, 2001). Greater variance of performing bride service (Lancaster, 1981; Chagnon,
among men is possible on the basis of raiding and 1988, 2000).
bride capture but the social system itself is not stra- The original distinction made by Orians (1969)
tified and individual men cannot amass or control between resource defense polygyny and harem defense
access to resources relative to other men or pass them polygyny is relevant here. The chronic warfare of
on to their sons. pastoralists (White and Burton, 1988; Manson and
Wrangham, 1991; Keeley, 1996) can be understood as
resource defense polygyny, as opposed to harem
Tribal pastoralism and extra-somatic wealth
defense polygyny described earlier for horticultural
For most of human history, humans depended on som- societies. Both types of societies raid to capture women
atic wealth or embodied capital to fund growth and to form polygynous unions (harems), but pastoralists
reproduction. However, the domestication of animals, also raid to capture resources that can be used to
particularly large herd animals such as cattle, camels, acquire and maintain new wives and their children.
and horses, had a profound effect on human social and In later socially stratified societies, successful male
reproductive patterns. Large, domesticated livestock resource holders do not have to do bride service, pay
have intrinsic qualities that affected human social bride wealth, or capture brides; brides will flock to
relationships, marriage patterns, and investment in them and their families will even pay for the opportun-
children. For the first time in human history, men ity for their daughters to marry such a quality male. In
could control a form of extra-somatic wealth that could a study of 75 traditional societies, the principal cause
be held by individuals, thus increasing the variance in of warfare was either to capture women (45% of cases)
male quality based on the resources each can control. or steal material resources to use to obtain (39% of the
Secondly, herds are the basis of a domestic eco- cases), particularly in pastoral societies where bride
nomy through their products of meat, milk and hides. wealth must be paid (Manson and Wrangham, 1991).
There are advantages to dependence on such a Resource defense polygyny means that males will
resource supply: (1) improvements in diets rich in compete to control the resources that females must
animal protein; (2) stability of diet since animals are have for successful reproduction. A male’s ability to
stored hedges against fluctuation in annual or seasonal successfully control more resources translates directly
climatic effects; and (3) flexibility due to the divisibility into more wives and children (Borgerhoff Mulder,
of herds into smaller units that can be moved about 1985, 1988b, 1989). One extraordinary result of extra-
the landscape on the basis of the richness and concen- somatic wealth, particularly readily partible wealth, is
tration of local resources (Barth, 1961). This improve- the institution of a new pawn on the marriage market
ment in diet may result in higher survivorship of table, bride wealth. Women and their families come to
women and children compared to foraging and horti- marriage negotiations with their traditional offers of
culture, but also results in higher mortality for males embodied capital (youth, health, fecundity, and female
due to endemic conflict. labor). Men, however, now have to come up with a
Large-animal herding demands a high degree of significant payment of extra-somatic resources in the
complementarity between female processing and child form of bride wealth as a preferred substitute for bride
care and male risk-taking in herd management and service. Men who depend on bride service are limited
defense. The products of herds require intensive proin their polygyny because of the years of service each
cessing of meat, milk and hides, labor provided by bride’s family requires. Men who inherit resources can
women. In contrast, the very existence of extra-somatic start their families early and marry often.
Bride wealth among pastoralists consists of horses, fewer wives than they could afford in the interests of
cattle, or camels with sheep or goats as supplements or providing each child with a greater endowment. In
lower-valued substitutes. Among African pastoralists other words, male pastoralists may pit quality against
the close male kin of the groom help him with his quantity of children to preserve a lineage status and
first bride-wealth payment, but the acquisition of sub- resource base and rather than simply maximizing the
sequent wives is his own responsibility. Livestock immediate number of descendents (Luttbeg et al.,
used for bride wealth has interesting attributes: (1) it 2000; Mace, 2000).
creates conflicts of interest between fathers and sons
and among brothers for its use to obtain a bride
Social stratification, states, and despotism
(Borgerhoff Mulder, 1988a); (2) men from poor fami-
lies will be more willing to take risks to obtain bride The rise of civilizations, beginning about 6000 years
wealth or brides though capture (Dunbar, 1991); and ago in Mesopotamia and occurring at different times
(3) livestock can be inherited. and places around the world (for example, Egypt in the
Investment in children takes a novel form under a Near East, the Aztec and Inca in the Americas, and
pastoralist system. The payment of bride wealth India and China in Asia) marked a critical shift in
improves health and survivorship among young girls how humans organized themselves in social systems
because their marriages bring in resources that can be and in relation to the environment (Goody, 1976;
used by their fathers and brothers to acquire more Betzig, 1993; Summers, 2005). These civilizations
wives (Borgerhoff Mulder, 1998). Sub-Saharan Africa appear to have developed independently in response
is notable for the fact that in spite of the patrilineal bias to local conditions without being the products of either
in so many societies, neither a survival nor a nutri- conquest or diffusion. In spite of this historical inde-
tional advantage is found for boys over girls (Svedberg, pendence, they evidence significant similarities: (1) the
1990). Furthermore, among the Kipsigis, who are agro- presence of large, stratified social groupings settled
pastoralists, early maturing (and presumably better fed on particularly large and productive resource patches;
and healthier) women have higher lifetime reproduc- and (2) the appearance of social despots, men who
tive success than late-maturing women. As a result, use coercive political power to defend their wealth
they command higher bride wealth and hence consti- and reproduction and practice warfare to acquire
tute a higher return on parental investment for their more resource patches and slaves (Betzig, 1986). These
upbringing (Borgerhoff Mulder, 1989). They also rep- two major effects flow from the nature of the resource
resent a better investment for a husband’s bride-wealth patches.
payment because of a higher return in fertility. The patches upon which the first civilizations were
Furthermore, children are able to provide child settled had special qualities: (1) they were highly pro-
care of younger siblings as well as low-skilled labor in ductive but set in environments where there was a
stock care and the processing of animal products, so rapid fall off to unproductive lands such as desert or
they are able to substantially but not completely offset forest; and (2) these productive patches could not be
the costs of their rearing compared to foragers (Bock, intensively utilized without complex political organiza-
2002a, 2002b). Child labor plays an important role in tion as in regional irrigation systems. Political control
the economies of both pastoral and agricultural soci- and organization rested on the power of men. Although
eties because their contributions through simple tasks female primates often form alliances with their female
such a carrying water contribute to food production by kin to protect and control access to the resources
freeing mothers to become more effective producers necessary for their reproduction (Isbell, 1991; Sterck
(Blurton Jones et al., 1994; Kramer, 2005a). However, et al., 1997), the reproductive benefits of extra-somatic
this reduction in cost of rearing is countered by the resources are much greater for men than for women,
fact the parents of sons now have a new cost to meet; because of their impact on polygyny. The end result of
the balloon payment (bride wealth) needed to establish these environmental conditions associated with early
sons on the marriage market. The flow of stock social stratification was that men competed for control
through families who are both bride-wealth receivers of the resources necessary for reproduction, formed
and givers helps maintain the system, at the same time despotic hierarchies involving social alliances and
that it creates problems for families with unfavorable stratification, with low-status men ‘agreeing’ to live
ratios of sons to daughters (Borgerhoff Mulder, 1998). under political despotism because they could not rea-
Finally and most significantly, there is suggestive dily move to another resource base.
evidence that for the first time humans begin to repro- The increased reliability of food resources, the
duce at levels that may not maximize the number of costs of warfare, and the concentrations of large popu-
descendents in association with the appearance of lations into small and sometimes urban areas each had
extra-somatic wealth and its inheritance. Among impacts on mortality and morbidity. A cross-cultural
modern East African pastorialists men appear to marry analysis of fertility and mode of subsistence found that,
for a 10% increase in dependence on agriculture by historic extremes in male variance in resource
between two related cultures one of which moves holding and power. As Betzig (1993) notes, the extreme
towards agriculture, there is a fertility increase of sizes of royal harems ranging from 4000–16 000
approximately 0.2 live births per women (Sellen and women are associated with smaller but still impressive
Mace, 1997). Bentley et al. (2001), in reviewing the numbers of wives and concubines for the royal rela-
cross-cultural and archaeological evidence, suggest a tives and supporters. In the case of the Inca the size of
series of multidirectional effects: higher fertility due to a man’s harem was regulated by law and in direct
more consistent food supply and earlier maturation; relationship to his social/political rank (Betzig, 1993).
increased infectious diseases with regular visitations Among the Inca there were nine levels of political rank-
as well as endemic diseases (malaria and tuberculosis) ings with polygyny ceilings for each except the top-
due to long-distance trade and large urban popula- most. These harems were exclusive holdings of large
tions; and a shift in peak mortality from infancy to numbers of young, fecund women with their children
middle childhood. Furthermore, warfare continues to and sexual access to them was restricted to their mate
reduce the numbers of young men in the mate pool. and regulated with some sophistication to optimize
With social stratification comes a complex division female fertility. Many of these wives and concubines
of labor with specialists in war, farming, crafts for the were collected as tribute or war booty; but others, as
production of goods and services, and war captives and principal wives, probably represented important poli-
slaves for the hardest manual labor, as well as long- tical alliances with their male relatives.
distance trade in luxury goods and slaves. The intro-
duction of the plow in Eurasia, perhaps as early as the
Variance in male quality and the marriage
sixth century BC, and the need for food production
market
beyond simple subsistence to service urban markets
led to significant changes in the division of labor There are two clear outcomes of such extreme variance
(Goody, 1976; Ember, 1983) and extremely high com- in male quality. The first is that many men remain
plementarity between male labor and resource acquisi- unmated or have only one wife, so that male celibacy
tion and female labor and child care. There is evidence or at least nonmarital sex is prominent. In the words of
of increased workloads for women in spite of the fact Dickemann (1981, p. 427), polygyny in the context of
that men assume more responsibility for farm labor, extreme social stratification is “characterized not only
because of increased demands for women to process by arbitrary sexual rights of lords and rulers but by
grains or secondary animal products such as milk, large numbers of masculine floaters and promiscuous
hides, and wool (Bentley et al., 2001). semi-floaters, beggars, bandits, outlaws, kidnappers,
Variance in male fertility in these first civilizations militia, and resentful slaves and serfs.” Nevertheless,
in the Near East, Central and South America, and Asia these early despotic states lasted for thousands of
was probably the greatest it has ever been before or years. A second outcome of variance in male resource
after in human history (Betzig, 1986, 1992a, 1992b, holding and male mating success is that there tends to
1993; Summers, 2005). The reason for this is that des- be universal marriage for women with only those most
potic males had enormous political and social control severely compromised by health or other personal
with the ability to eliminate rivals and their entire qualities being unlikely to find a role as secondary wife
families through despotic edict, to wage war to or in a minor union. For access to the mating market
increase personal and state resource bases, to acquire men must bring extra-somatic wealth, power, and land
slaves and war captives for labor and reproduction, in order to be favorably placed or else get wives as
and to determine political succession for favored sons. high-risk booty in state warfare (Low, 2000; Clarke
This extreme variance in male resource holding inevit- and Low, 2001).
ably produces social and political instability due to the Women, too, bring their traditional embodied capi-
creation of too many potential heirs (sons of many tal qualities of youth, health, and fecundity along with
wives) and too many males (slaves) without access their labor for access to the marriage market. However,
to the means of reproduction. The great wealth to be there was a historic shift in how women and their
gained from domination also motivated expansion and families approached marriage negotiations that has
intergroup conflict among would-be despots. been richly described by Dickemann (1979a, 1979b,
Despotic males are an extreme example of resource 1981) in a series of papers on hypergyny, dowry, female
defense polygyny (Orians, 1969); that is, as individuals infanticide, and paternity confidence. The extreme
they control access to the resource base for reproduc- variance in male quality created by despotism and
tion that females require and, with few competitors, harem polygyny forces the families of women to put
polygynous marriages to them become the only family down more and more value on the mate market table to
formation strategy option for many women. The access a desirable groom or to move a daughter up in
mating markets of despotic systems are characterized the social hierarchy. These extra payments include
actual wealth, in the form of dowry, and guarantees estate intact and maintain the concentration of wealth,
of paternity confidence (bridal virginity and wifely or in the case of the poor, to balance food supply with
chastity). Guarantees of a daughter’s virginity and family size. This trend, although it occurred in
chastity (a prerequisite for a bride destined to produce response to population pressure on existing resource
heirs to a male lineage holding a reproductive estate) bases all over the world at different time periods, is
are costly forms of embodied capital, involving female particularly well documented in premodern Europe.
seclusion (special women’s quarters, harem guards, Human evolutionary ecologists in collaboration with
chaperones), and female incapacitation (foot-binding historical demographers provide us with a unique
and corseting) that bars their daughters from the out- record of the relationships between fertility, family
side world of productive labor. formation strategies, and socioecological context
Parental concern over the ability of their children during the premodern and early modern periods of
to access reproductive estates transformed the nature European history (Voland, 2000). Their studies, based
of the marriage market. Parental investment in these on heraldic or parish records of births, marriages,
systems varies in relation to the power and wealth deaths, and inheritance of estates, can be used to dir-
of the male’s family. As is to be expected, under such ectly link reproductive strategies with resource hold-
conditions where male access to and control of ings. This time period witnessed developments that
resources is the basis of social stratification, patrilineal had began centuries earlier but occurred without the
descent and patrilocal residence are highly favored benefit of quantifiable documentation. Boone (1986a,
since males are the principal resource holders 1986b), for example, traces the historic process of par-
(Hartung, 1982). Resource-holding parents commit ental investment among Portuguese elites during the
to a “balloon payment” in launching their children late medieval/early modern periods of the fifteenth and
in marriage. This balloon payment takes the form of sixteenth centuries. Saturation and resource stress are
endowments and promised inheritance for sons and evident with a progressive narrowing of the numbers of
dowry as anticipatory inheritance for daughters claimants to an inheritance, first through monogamy
(Goody, 1973, 1976; Dickemann, 1979a, 1979b). For to create a single bloodline of inheritors and bastardy
resource-holding families then, the marriage market to disenfranchise offspring who are not the product of
formed by stratified social systems proved costly in a legitimate union (Goody, 1976, 1983), followed by a
terms of parental investment and forced a focus on preference for sons over daughters as inheritors,
endowments for both sexes at the age of marriage. and finally by birth order effects with preference for
Poor parents, on the other hand, attempted to balance primogeniture within each sex for access to resources
labor demands with fertility, since in agricultural and the creation of celibate children to live as priests,
systems children can be productive at low skill tasks nuns, bachelors, and spinsters (Hrdy and Judge, 1993).
or child care and add to the family economy. Thus, For the first time in human history mating and
they might try to regulate birth spacing to optimize reproduction is no longer a universal for women and
the productivity of already born children before siblings of the same sex are pitted against each other
another mouth to feed is added to the family. in competition for access to reproductive estates. With
Finally, a notable characteristic of the premodern survival through child- and young adult-hood still quite
period in many parts of the world is evidence for a problematic, ancillary practices develop in which both
growing rural population resulting from higher fertility sons and daughters would be held in reserve in monas-
and an associated growing concern regarding satu- teries and nunneries for inheritance and reproduction
ration of the resource environment. This is often should their older same-sex sibling die (Goody, 1976,
associated with urban growth, empire building, and 1983; Boone, 1986a, 1986b). Within the scope of these
expansionism, providing opportunities for migration restrictions that limit half-sibling and sibling compe-
by noninheriting or low status children to areas of both tition, parents with wealth raise as many children as
higher mortality and risk but also with the potential they can but endow a select number at adulthood.
for the acquisition of land, or wealth and power. It During most of this historic period there is a strong
also generated a new concern about keeping the correlation between wealth, probability of marriage,
family estate intact and about the management of younger age at marriage, and completed fertility (Voland,
inheritance. 2000). However, restricted inheritance decreases
the reproductive benefits of polygyny. The desire to
concentrate wealth also limits the reproductive suc-
Premodern states and narrowing the pool
cess of noninheriting sons and daughters. This is a
of inheritors
second striking example in which reproductive and
With population growth and increased saturation of parental investment behavior in response to extra-
arable lands, parents adopted patterns of restricted somatic wealth results in outcomes that did not
and differential inheritance in order to keep the family maximize parental fitness. In fact, towards the end
of the period, as life expectancy improved and eco- whose main function was to produce heirs, to a nearly
nomic structures became saturated, resource holding annual birth rate (among the highest for any group
groups delayed marriage into the late 30s and early of women in human history). In contrast, the birth
40s for men and mid 20s for women (Szreter and spacing for wet-nurses was closer to four years (Hrdy,
Garrett, 2000; Voland, 2000). 1994). A second group of women also used wet-nurses,
The family reconstruction studies document very especially towards the end of this historic period.
different reproductive strategies according to class1. These were single women working in urban centers or
Generally, wealth brings higher probability of marriage, the wives of poor tradesman who found themselves in
at a younger age, to a younger spouse, and more positions of servitude or trade where the incompatibi-
children. However, as environments become more lity between breast-feeding and work was complete.
saturated, local resource competition among siblings To the great detriment of their infants’ survival, these
differentially affected resource-holding families, as women placed their children with commercial wet
opposed to day laborers, and increased the likelihood nurses at baby farms (Hrdy, 1994). In these cases the
of dispersal of later-born children (Clarke and Low, demands of maternal work far outweighed the needs
1992; Voland and Dunbar, 1997; Towner, 1999, 2001). of infant growth, perhaps to improve the development
With saturation, the benefits to resource holders of of weaned, older children.
having an above average number of children was offset The past 10 000 years of human history brought
by more and more intense sibling competition for many changes to what was originally the forager adap-
access to inheritance (Voland, 2000). Parents without tive niche. As the last glaciers withdrew, humans began
resources had no need to manipulate their offspring to intensify their extraction of resources from the
and were more likely to benefit from opportunistic environment by domesticating plants and animals. At
strategies by their children (Voland and Dunbar, 1995). first, land extensive horticulture combined with
Wet-nursing presents a fascinating example of hunting did little to alter the human experience of
how differentiation in parental investment strategies small groups, face-to-face social networks, and subsist-
develops into extreme forms for both the highest and ence economies. Family formation practices continued
the lowest status groups of women. Throughout the relatively low rate of polygyny, nearly universal
human history there has always existed a conflict marriage, bride service and bride capture, and the
between production (acquisition of food) and repro- production of children regulated only be the health
duction (lactation and child care) for women, a conflict and well-being of the mother and each child.
that in fact troubles female mammals in general. The first transformation in human experience
Human women are especially caught in this conflict followed from the appearance of extra-somatic wealth
because they have multiple, dependent young of in the form of large domesticated animals and later
differing ages and needs (Draper, 1992), which means land. Extra-somatic wealth has an intrinsic quality, it
that true respite never occurs until all children are can be taken by force and stronger individuals and
reared. Cross-culturally women’s work is organized by groups can amass or control access to it. This neces-
its compatibility with child care (Brown, 1970); how- sarily creates much wider variance in male quality than
ever, this compatibility is never complete – only more occurs in forager men dependent on embodied capital
or less so (Hurtado and Hill, 1990; Lancaster, 1997; investments of health, vigor, and skill. Family forma-
Lancaster et al., 2000). As a result of social stratification strategies responded by turning the old rules
tion high status women are able to subvert the physio- upside down. Instead of men paying for access to wives
logical capacity of lactation of other women to serve with bride service, bride wealth, or the dangers of bride
their own reproductive ends. Since intense breast- capture, payments in the marriage market reversed
feeding lowers the likelihood of ovulation, a wet-nurse, direction. As social groups became stratified and
even if paid, sacrifices her own fecundity to another wealth differentials increased, women and their fami-
(Hrdy, 1994, 1999). Typically high status women did lies began to bring and more to the bargaining table by
not breast-feed their own children but used wet-nurses. offering both dowry and paternity confidence in the
This increased the fertility of high status women, form of virginity and chastity. During the final phase
of the premodern period, societies became obsessed
with the preservation of the family’s reproductive
1
The behaviors of nobility are documented by Boone in Portugal estate by successively narrowing the possible number
(Boone, 1986a; Kramer, 1998) and Dickemann in Europe, the of inheritors. First the line of inheritance went only to
Middle East, China, and India (Dickemann, 1979b, 1981), and
for gentry and land-holding peasants as well as day laborers by the children of the principal wife with others labeled
Voland and colleagues in Germany (Voland, 1990; Voland and with bastardy, then daughters could only inherit via a
Engel, 1990; Voland et al., 1991, 1997; Voland and Dunbar, dowry lower in value than a son’s inheritance, next
1995, 1997; Voland and Chasiotis, 1998; Voland, 2000), Low in
Sweden (Low, 1990, 1991, 1994), Towner in the United States, only the first or a selected son could be endowed with
and Hughes (1986) and Scott and Duncan (1999) in England. the family estate and the rest had to find other niches
in the society or migrate. Just before the onset of mod- Not all the world today has experienced the demo-
ernization, the world had become full of bachelor and graphic transition, but completed family size of
spinster noninheriting children with no guaranteed replacement level or less is typical of modern econo-
access to the right or means of reproduction, qualities mies with skills-based labor markets as in Western
of life that were part and parcel of the original human Europe, North America, Japan, China, and parts of
adaptive niche. Latin America (Cuba, Chile, Costa Rica, Puerto Rico,
and Trinidad and Tobago) (Population Reference
Bureau, 2008). Furthermore, for the first time the
The modern world and embodied capital
world population is evenly divided between rural and
Given rural reproductive and survival rates, the urban areas, and by 2050 urban residents are likely
restricted inheritance system discussed in the previous to make up 70% of the world’s population (Population
section produced excess adults without access to land Reference Bureau, 2008). This reversal in family repro-
and the means of production. Colonization through ductive strategies from having as many children as
conquest was one response by males to this situation, possible to only two is related to a strategic shift
especially later-born sons (Boone, 1986a, 1986b; from quantity to quality, in which quality is most often
Curtin, 1989). Another response by both men and expressed in education and training to be used for
women was to provide services for others, and migra- access to resources, not inheritance.
tion to cities in search of employment. This supply of
labor and of consumers helped fuel the growth of a
Modern skills-based labor markets and the
skills-based, mercantile economy that was to gradually
expenditure of extra-somatic wealth
supplant the power- and land-based hierarchies of
to embody human capital
the premodern period based almost entirely on extra-
somatic wealth. Changes in the nature of resource production and
Those conditions set the stage for dramatic changes the economic forces that determine wages in labor
in reproductive and parental investment strategies. markets appear to underlie these changes in reproductive
In the early 1800s, changes in the relationship between and parental investment strategies, and explain their
humans and their economies began in a small part of patterning over time and space. The directional change
the world, Western Europe, including England (Clark, in the nature of labor markets towards greater wage
2007). This change has been labeled the “demographic premiums for skill- and education-based capital over
transition.” For nearly all of human history, available the last two centuries is well documented (Newcomer,
evidence suggests that human populations responded 1955; Burck, 1976; Herrnstein and Murray, 1994;
to greater resource availability with increased fertility, Vinovskis, 1994; Clark, 2007). As the extent of the labor
and reduced fertility when resources were scarce. and consumer markets grew, along with advances in
Women’s reproductive physiology appears well production technologies, there was a concomitant
designed to make adaptive responses to increases and increase in both private and public investments in educa-
decreases in energy availability (Ellison, 2001, 2003). tion. In a sense, the relationship between embodied
However, after 1800 with the demographic transi- capital and production in modern skills-based labor
tion, the size of human families began to shrink, first markets is more similar to the foraging life way than to
among the wealthier segments of society, even as stan- its agricultural predecessor. Rather than generating
dards of living and energy availability were increasing. wealth through control of land, people now invest in
Unlike before when individuals in good condition had learning to increase productivity, and individuals are free
more progeny than individuals in poor condition (just to move through the environment in search of economic
as is the case with other species), higher status humans opportunities because they carry their embodied capital
began having fewer children than did the poor. with them.
This trend only lasted for a time. Today there are These increases in educational capital investment
remarkably few differences between classes or even and the nature of labor markets were accompanied by
ethnicities in completed family size. For example, in improvements in the “technology” of disease preven-
the United States today the average US woman tion and treatment, and by increased public and pri-
produces 1.9 children, considerably below the replace- vate investments in health and mortality reduction.
ment level of 2.2 children. When broken down by During the nineteenth century, there were large changes
ethnicity, the numbers are 1.7 for Asian Americans, in the scientific understanding of disease (Preston and
1.8 for non-Hispanic Whites, 2.0 for Blacks and 2.3 Haines, 1991). This led to a dramatic decline in infant,
for Hispanics (US Census Bureau Report, 2008). child, and adult mortality rates that continued for
Although the range between the highest and the lowest close to a century. As scientific advances enabled
is three-fifths of a child, the main message from this reductions in mortality rates, there was strong pressure
data is consensus: two children are enough. to increase public investments in health and disease
prevention from the protection of the water supply 1995). For example, Hart and Risley report that, by
to the development of vaccines and public access to the age of three, children have heard six million words
medical care. As a result, infant and child mortality if their mothers are professionals, three million
rates reduced dramatically, greatly increasing the words if their mothers are “working class,” and only
probability that investments in children will be realized one million words if their mothers are on welfare. By
in terms of productive adulthoods. The length of the the time children enter the public education system
productive adult life span, especially when time lost to there are clear differences among them in school-
morbidity is taken into account, also increased signifi- related skills, and those differences are related to socio-
cantly. Together, the two shifts in production processes economic status.
and mortality rates favor increased human embodied Second, the rate at which a child learns may
capital investment in a way that is reminiscent of the depend on the knowledge and skills she already pos-
initial dietary shift leading to the hominid specializa- sesses. Much of the education offered in schools is
tion discussed above (Kaplan et al., 2002). based upon the premise that knowledge is cumulative
This historical process also resulted in much (Cromer, 1993). Basic skills are acquired first, and
greater labor force participation by women. During those skills are used as a foundation for the acquisition
the initial demographic transition in the developed of the next set of skills. This implies that the impact
world, the breadwinner–homemaker family structure of the child’s time inputs would depend upon skills
was dominant. With increased demand for labor that already in place. It also means that the net increase
requires skill as opposed to strength and with growth in embodied capital at each age is a function of both
in the service sector of the economy, wage-earning the quality of inputs, and the embodied capital
opportunities for women increased. At the same time acquired at younger ages.
the payoffs to “home” production decreased with Moreover, those qualities tend to be correlated
labor-saving devices, such as washing machines and across inputs. Children with more educated parents
refrigerators, and smaller family size reduced the also attend better schools with better teachers and
number of years spent caring for small children. Over better fellow students. At the other extreme, children
time the value of male strength through labor and the in developing nations often come from families in
time women spent caring for small children was which neither parent has had formal schooling and
reduced; thus leading to a trend from greater to lesser attend schools with very large class sizes, almost no
complementarity between men and women so that library resources, and teachers with only primary edu-
men and women are now closer to being interchange- cation themselves. Under those conditions, much less
able units in work effort. is learned per year spent in schooling. For example, in
Although the shift towards an education-based a study of a predominately Black township school in
wage structure has been largely monotonic, those Cape Town, South Africa, Anderson, Kaplan and Lam
changes occurred at different times in the developed (unpublished manuscript) found that on average, it
and developing worlds and the details of the supply took children 15 years to complete 12 grades of
and demand for labor of different levels of human schooling. By that age (20–21), only about 10% of
capital have been both historically and regionally vari- students have passed the final matriculation exam
able. Moreover, both within and among societies, there and earned a high school diploma. The variance in
appears to be a great deal of variation in rates of return those inputs leads to an increasing differentiation in
on investments in educational capital. educational capital with age.
The production of human capital is also human- This within-population heterogeneity in the costs
capital intensive (Becker and Barro, 1988) and associ- of embodying capital in children means that the envir-
ated with a reduction of the value of children’s labor as onment does not determine diminishing returns to
their time is taken up with education and training. To parental investment as it would be in primary produc-
see this, it is useful to think of an “education production economies, but will be frequency-dependent. Indi-
tion function.” In each year of a child’s life the amount viduals with low levels of human capital are more likely
a child learns, and the changes in his or her knowledge, to be unemployed as well as having a lower income,
reading, writing, logic, and mathematical skills, will when employed. This is especially true in urban areas
depend upon many different inputs, such as the child’s in the developing world. The massive rural to urban
time, prior abilities, parents’ time, and teachers’ time. migration over the last four decades has resulted in
The value of those inputs, in terms of the educational very large populations of people with low levels of
capital produced, depends on the quality of in those education competing for a limited number of low skill
inputs. First, consider inputs of parents’ time. There is jobs in the economy. In many places, male unemploy-
significant evidence that the nature of parent–child ment can be as high as 70% or more. This variability
interaction varies with the educational level of parents in educational capital, along with its impacts on
(Hart and Risley, 1995; Hoff-Ginsberg and Tardiff, income variation both across individuals and within
individuals over time, has profound effects on family investment patterns typical of most mammals? How
formation and reproduction. did it alter how humans access and distribute food?
In fact, the link between education and income 2. What is the impact of the socioecological context
increased in intensity during the second half of the on human marriage markets and family formation
twentieth century. For example, real wages actually strategies in terms of the distribution of resources
dropped from 1958 to 1990 among men without high and the means to access them?
school degrees in the United States. In 1958, men with 3. More and more modern societies are experiencing
graduate education earned about 2.3 times as much as a reduction of completed family size to replace-
men with elementary education; by 1990, they earned ment level (2.2 offspring) or below. Why should
more than 3.5 times as much. Wage differentials this be so when these societies have the highest
among men with some college education, bachelor’s standard of living known in human history? How
degrees, and graduate degrees also increased substan- might such small family size impact parental
tially. For women, wage differentials among educa- investment and family formation patterns?
tional attainment levels increased substantially in the 4. Why does variation in male quality impact the
1980s (Kaplan et al., 2002). marriage market? What features in male quality
have been important in different kinds of econ-
omies and social organization? Are these qualities
THE HUMAN ADAPTATION: SOMATIC AND inherent or acquired? How so?
EXTRA-SOMATIC INVESTMENTS 5. What are the factors that have led to a division of
labor in which female work is closely linked to
Human history is based on a remarkable coevolved compatibility with child care? Are these factors as
pattern of investment in a large brain, slow growth, salient today as in the past?
long life, and access to resources based on skills-based 6. Embodied capital has been critical to human
performances. This pattern, along with marriage, a affairs in both the simplest and most modernized
complementary division of labor between the sexes, societies. What are the similarities and differences
food-sharing, and the support of offspring well into in embodied capital in these two contexts?
adulthood, has allowed humans to people the world
and control the top of the food chain wherever they
go. Most of the human history of the past two million
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Part V
Health and Disease
“The deviation of man from the state in which he was

originally placed by nature seems to have proved to
him a prolific source of diseases.”
Edward Jenner (1749–1823)
457
27 Evolutionary Medicine, Immunity,
and Infectious Disease
The purpose of this chapter is to provide readers with and pathogen virulence. Finally, the evolutionary
introductions to several topics central to a modern histories of several key pathogens are discussed, spe-
understanding of human evolutionary biology. Infec- cifically to illustrate the human host adaptations, both
tious pathogens have placed critical selective con- biological and behavioral, to disease emergence and
straints on the evolution of our hominin ancestors, evolution. Review of such a diverse topic produces an
and our own species continues to coevolve with infec- admittedly large reading, but it is hoped that readers
tious organisms today. Our understanding of the pro- may use this as a source for further discussion and
cesses that shaped this evolutionary struggle have development.
changed, and now an adaptationsist perspective
offered by the discipline of evolutionary medicine
helps to shed light on our vulnerabilities to infectious EVOLUTIONARY MEDICINE
diseases and noninfectious degenerative diseases. It
also aids in our understanding of the purpose and The central role of disease in human evolution was
outcomes of our coevolutionary conflicts with the queried decades ago by John Burdon Sanderson Hal-
microscopic predators that parasitize us. So as to com- dane (1892–1964). He hypothesized that much of the
pete in these interactions, we have developed a marvel- biochemical diversity found in serological studies of
ously complex immune system capable of dynamic, humans likely played important roles in disease resist-
varied responses. Insight into these mechanisms ance (Haldane, 1949). Today, the integration of medi-
provides fascinating examples of real-time Darwinian cine and evolutionary biology forms the basis of the
processes of survival and fitness maximization in the discipline of evolutionary, or Darwinian, medicine.
face of invading competitors within the human host. This field recognizes that medical research can benefit
Interestingly the ontogeny and deployment of these significantly from a priori understanding of adaptation
responses are dependent on several factors, including by natural selection and its role in the causation of
genetic and ecological constraints. health-related outcomes. This might include under-
The discussion offered below provides an introduc- standing the various adaptations we use to combat
tion to evolutionary medicine with the specific purpose pathogens as well as the adaptations that pathogens
of better understanding human-pathogen coevolution use to counter our own defense mechanisms. This also
and the development of human immune responses. includes understanding the necessary costs imposed by
A current, detailed description of human immunity is our current adaptations against disease, and that there
included, but this discussion is far from complete. are mismatches between our current form, which
Comparative aspects of evolutionary immunology are evolved in the past, and the present environments in
emphasized, as are the genetic and ecological sources which we find ourselves (Williams and Nesse, 1991).
of variation in these responses. Immune functions have Whereas current medial research and practices focus
played important roles in the evolution of organismal on describing how we become ill with the purpose of
life histories and so our discussion includes how identifying cures and preventions, evolutionary medi-
immune mechanisms could be selected for via natural cine utilizes the adaptationist perspective in evolution-
and sexual selections, develop according to environ- ary biology to describe why some people get sick in
mental exposure and genetic factors, and then be different environments. Caution must be used in over-
maintained through trade-offs and constraints. Basic applying an adaptationist paradigm in evolutionary
aspects of epidemiology are also introduced but with medicine (Marks, 2008), but we must still ask what
particular emphasis on host–parasite coevolution and its aspects of our physiology, morphology, and behavior
consequences for the evolution of antibiotic resistance make us vulnerable to disease, why have these traits
459
460 Michael P. Muehlenbein
TABLE 27.1. Some manifestations of disease benefit the host whereas others benefit the invading pathogens.
Adapted from Nesse and Williams (1996).
Observations Examples Primary beneficiary
Hygienic measures Killing mosquitoes, avoiding detritus Host

Host defenses Immune responses, sneezing*, vomiting* Host
Repair of damage Regeneration of tissue, inflammation* Host
Compensation for damage Chewing on opposite side to avoid tooth pain* Host
Damage to host tissue Liver damage from hepatitis* Neither
Impairment of host Decreased detoxification, lameness* Neither
Evasion of host defenses Molecular mimicry, change in antigens Pathogen
Attack on host defenses Destruction of host cells* Pathogen
Uptake and use of nutrients by pathogen Growth and proliferation of pathogens Pathogen
Dispersal of pathogen Transfer of blood parasite to new host by mosquito Pathogen
Note: *Some manifestations could benefit both the host and pathogen.
evolved, and why do they persist today? Evolutionary Some traits may have evolved as design comprom-
medicine attempts to emphasize the ultimate or evolu- ises. In this case, a trait may have been beneficial in an
tionary explanations for medical phenomena rather than ancestral environment, but is no longer beneficial in
just the proximate causes of morbidity and mortality. the current environment, and disease can result from
For a more complete review of evolutionary medi- this mismatch (the “discordance hypothesis”). For
cine, readers are encouraged to utilize the following example, a preference for fat, carbohydrates, and salt
texts: Nesse and Williams (1996), Ewald (1996), in the ancestral hominin diet was beneficial, but may
Trevathan et al. (2007), Elton and O’Higgins (2008), now result in cardiovascular disease and metabolic
Stearns and Koella (2008). In brief, evolutionary disorders in modern, developed environments with less
explanations for disease can be organized into several physical activity (Eaton and Eaton, 1999). Some traits
categories, including defense mechanisms, design may be evolutionary legacies that evolved in the past,
compromises, and conflict between organisms but can predispose individuals to illness in the present.
(Williams and Nesse, 1991; Nesse and Williams, Immunoglobulin E (IgE), eosinophils, mast cells, and
1996). Defenses are mechanisms that have evolved to other proximate mediators of allergic responses likely
prevent, limit, or eliminate disease, and we must rec- evolved to protect us against helminth and other extra-
ognize which are signs and symptoms of disease that cellular infections. Improvements in sanitation and the
materialize to benefit the invading pathogen, which are absence of these infections in most people in developed
manifestations of disease that are actually beneficial countries may produce an imbalanced Th-cell immune
host responses shaped by natural selection to defend phenotype (see below), and our systems overreact to
against infection, which are side effects of infection/ novel and largely unimportant allergens, like dust
disease, and which mechanisms benefit both the host mites (Yazdanbakhsh et al., 2002). Thus our evolution-
and pathogen (Table 27.1). Although they may be ary legacy may be a hypersensitivity response that now
unpleasant, if they are actually beneficial host predisposes us to atopy.
responses, then blocking these mechanisms may cause The propensity for drug abuse is also likely a design
more harm than good. Fever, nausea, and vomiting compromise and the result of a mismatch between our
during pregnancy, revulsion towards odors associated bodies and modern environments: humans are vulner-
with bacterial decomposition, and mental conditions able to abuse of psychoactive drugs because these sub-
like fear of snakes and heights have all been proposed stances mimic the activation of neural mechanisms
to be defensive mechanisms that evolved to increase involved in regulating feelings of pleasure and other
host fitness. For example, fever may make it more necessary emotions (Nesse and Berridge, 1997). We
difficult for certain pathogens to multiply within the have been programmed by natural selection to pursue
host, and elevated temperatures may also optimize behaviors that produce such chemical incentives.
immune cell activity of the host (Kluger et al., 1998). Unfortunately, these substances are now available in
Inhibiting or reducing fever during infection may not forms, concentrations, and delivery systems that all too
be very beneficial in certain circumstances (Doran potent and readily available. Evolutionary consider-
et al., 1989; Graham et al., 1990; Kramer et al., 1991). ations suggest that “we cannot reasonably expect to
Of course, high fevers can cause much more than just win the war on drug abuse, but we can use our know-
discomfort, including sterility and death. ledge to develop sensible strategies for prevention,
Evolutionary Medicine, Immunity, and Infectious Disease 461
treatment, and public policy to manage a problem that considering infectious diseases, their evolution, and
is likely to persist because it is rooted in the fundamen- our immune responses to them.
tal design of the human nervous system” (Nesse and
Berridge, 1997, p. 65). Furthermore, psychoactive sub-
stances that inhibit all negative emotions can also HUMAN IMMUNITY
impose fitness costs. Nonpathological low mood and
anxiety may be beneficial in some situations, forcing Immunity is obviously vital for defense against invad-
individuals to remove themselves from potentially ing pathogens, cellular maintenance, and renewal and
harmful circumstances (Nesse, 2006). protection against cancer. No discussion of infectious
Despite contributing to morbidity and mortality, diseases would be complete without an introduction to
some genetic and phenotypic traits can be maintained the immune system and its responses. For a compre-
in a population because they are beneficial in some hensive description of immunology and human
forms or in certain environments. Of course, some immunity see Paul (2008), and for a brief review see
genes can be maintained in a population due to novel Delves and Roitt (2000a, 2000b). Here I provide readers
mutations, genetic drift and other random processes, with an introductory review of the human immune
or because they are very rare disorders. Many disease system and its complex responses. Comparative
conditions are caused by organismal defects, and aspects of evolutionary immunology are emphasized
these may be transmitted to future generations and as are the genetic and ecological sources of variation
maintained in the population because they do not in these responses.
affect people until after reproduction (Haldane, 1941;
Medawar, 1952). Nonetheless, there are trade-offs
Innate immunity
in which traits can exhibit antagonistic pleiotropic
functions, including some which are beneficial, The mammalian immune system is usually organized
particularly in the genetic heterozygous state. For into two primary components: innate (constitutive) and
example, individuals that are heterozygous for alleles adaptive (acquired) immune responses (Figure 27.1).
on chromosome 7 (e.g., dF508, W1282X, 1677delTA) Innate immunity consists of primary nonspecific, gen-
which code for cystic fibrosis may better resist disease eralized mechanisms that block or eliminate foreign
from Vibrio cholerae, Salmanella typhi, Escherichia particles from invasion of the host. Such defenses
coli, and even Mycobacterium tuberculosis (Poolman include anatomical barriers (mucus membranes, skin),
and Galvani, 2007). resident flora (nonpathogenic bacteria), humoral
Organisms are shaped by evolution in ways that factors (lysozyme, complement, and other acute phase
can make disease almost inevitable. Autoimmune proteins), and cells (phagocytic cells like neutrophils,
diseases, such as type I diabetes, rheumatoid monocytes, and macrophages; inflammatory medi-
arthritis, and multiple sclerosis, can result from ators produced by basophils, mast cells, and eosino-
overactivation of immune responses which become phils; and natural killer cells) (Delves and Roitt,
targeted towards an individual’s own antigens. 2000a). Note that white blood cells (leukocytes) include
Increased risk of leukemia may even be a price we macrophages, dendritic cells, granulocytes (eosino-
pay for maintaining intricate and powerful immune phils, basophils, and neutrophils) and lymphocytes
responses that would help to control microbial infec- (T cells and B cells). All leukocytes originate from
tions (Greaves, 2006). Maintaining high testosterone hematopoietic stem cells in bone marrow.
in mammalian males can augment male reproductive Macrophages are mononuclear phagocytes that
effort by increasing musculoskeletal performance perform many tasks, such as phagocytosis, cytokine
(which aids in work capacity, intersexual competi- secretion, chemotaxis, and antigen processing and pre-
tion, intrasexual coercion, and mate choice) but can sentation (Hume et al., 2002). Interdigitating dendritic
also compromise survivorship by increasing risk of cells function in antigen presentation (Medzhitov and
prostate cancer, production of oxygen radicals, risk Janeway, 1997). Toll-like receptors on macrophages
of injury due to hormonally augmented behaviors and dendritic cells bind to foreign antigens and initiate
such as aggression, violence and risk taking, reduced the cascade of innate and adaptive immune effector
tissue and organ maintenance, negative energy mechanisms (Visintin et al., 2001). Eosinophils attack
balance from adipose tissue catabolism, and sup- extracellular parasites by the release of various chem-
pression of immune functions (Muehlenbein and ical mediators (Wardlaw et al., 1995). Basophils and
Bribiescas, 2005; Muehlenbein, 2008a). These are mast cells facilitate atopic, inflammatory reactions
compromises that our genotypes and phenotypes (Abraham and Arock, 1998). Natural killer cells attack
have made through evolutionary processes, and the membranes of infected or malignant target cells
understanding this can be insightful for medical through a variety of processes, including antibody-
research and practices. This is especially the case in dependent cellular cytotoxicity (Herberman et al.,
Major immune mechanisms in

humans
Innate immunity Adaptive immunity
Lymphocytes
Health behaviors
B cells (antibody-mediated T cells (cellular-mediated

Anatomical barriers, resident immunity) immunity)
nonpathogenic bacteria
Immunoglobulins Cytotoxic T cells Helper T cells

Interferon, lysozyme, lactoferrin, (CD4)
(IgG, IgM, IgA, IgD, and IgE) (CD8)
transferrin, heat shock proteins
Proinflammatory Th-1 cytokines

Complement system (IFN-γ, TNF-α, IL-1β, IL-2, IL-12)
Macrophages, neutrophils, basophils, mast cells, Anti inflammatory Th2 cytokines

eosinophils, natural killer cells, dendritic cells (IL-4, IL-5, IL-10)
Immunosuppressive Treg cytokines

(IL-10, TGFβ)
27.1. Many of the major immune mechanisms in humans.
1986). Interferon is produced by virally infected cells to attack complex and a cytolytic response (Law and
signal apoptosis and prevent infection of adjacent cells Reid, 1995).
(Samuel, 2001). Heat shock proteins are intracellular
molecules that, among other functions, aid in antigen
Adaptive immunity
presentation and stimulation of proinflammatory
responses (Robert et al., 2003). Lactoferrin, transfer- Because of the extreme diversity and short multipli-
ring, and other proteins bind circulating iron, limiting cation times of most pathogens, hosts are under inten-
availability during bacterial infections (Baker et al., sive selection pressure to produce variable defensive
2002). Innate immunity also includes resident flora in responses. This is accomplished through the high
the gut and other tissues that prevent pathogen colon- diversification and rapid responses of acquired, spe-
ization. Health behaviors that decrease the likelihood cific immunity. In this case, effector mechanisms allow
of illness, such as handwashing and avoidance of fast, secondary responses during subsequent expos-
detritus, might also be included in the category of ures. First, foreign antigens are recognized by immune
innate immunity, although most of these behaviors cells in the tonsils, adenoids, and Peyer’s patches after
arguably have a learned component. inhalation or ingestion. Foreign substances are trans-
The complement system includes enzymes that ported in the lymph and trapped in the lymph nodes or
function to eliminate microorganisms by promoting transported in the blood and filtered by the spleen. In
inflammatory responses, such as changes in local vas- these locations, lymphocytes react with specific patho-
cular permeability and entry of immune cells into gen antigens and facilitate an adaptive immune
infection sites. Complement also functions in lysis of response. Peripheral circulation of lymphocytes also
foreign cells through the formation of membrane allows for continual monitoring of infection and injury
attack complexes, and in mediation of phagocytosis in strategic sites throughout the body.
through the coating (opsonization) of pathogens and Lymphocytes come in two main forms: B cells and
infected cells (Carroll, 1998). Complement is also T cells. All lymphocytes are produced in bone marrow
important for stimulating adaptive immune responses and the fetal liver, but the maturation of T cells takes
(Dempsey et al., 1996). Within mammals, the presence places in the thymus. During development, those T and
of foreign molecules activates one of three different B cells that auto-react to self-antigens (estimated at
complement pathways (innate ¼ alternative and lectin; 98% of all T cells) are eliminated in the process of
adaptive ¼ classical). In most cases, the C3 component thymic education to minimize self-reactivity (Sprent,
binds to foreign molecules and activates phagocytes 1993). Positive selection for developing T cells involves
and other complement components (approximately downregulating signals that would otherwise induce
30 different proteins) that produce the membrane apoptosis if auto-reactivity occurs, resulting in
tolerance of self-antigens. Negative selection involves Thomson, 2001). The HLA superlocus is located on
induction of apoptosis in T and B cells that autoreact chromosome 6 (Fischer and Mayr, 2001).
with self-molecules on antigen-presenting cells Antibodies are glycoproteins that neutralize patho-
(macrophages and interdigitizing denditic cells) in the gens and their products, block binding of parasites to
thymus (Rathmell and Thompson, 1999; Sebzda et al., host cells, induce complement activation, promote cel-
1999). Without the ability to distinguish between lular migration to sites of infection, and enhance
self and nonself tissues, immunopathology due to phagocytosis, among other actions. Antibodies in
autoimmune disease would rampantly consume the mammals are composed of two light chains (with
individual. The ontogeny of lymphocytes therefore single variable [V] and joining [J] elements) and two
invokes Darwin’s principles of natural selection in evo- heavy chains (with single variable [V] and joining [J]
lutionary processes that occur within an organism. elements, and multiple diversity [D] elements) bound
The development of the immune system begins together by disulfide bonds (Edelman, 1973). The vari-
early in gestation (Remington and Klein, 1990). able end interacts with antigens whereas the constant
Acquired immunological characteristics (particularly region determines the class and subclass of antibody:
immunoglobulins G and A) are transferred from IgG, IgM, IgA, IgD, and IgE. In general, IgG is the most
mother to offspring via the placenta and breast milk predominant in circulation and some of its functions
(Keller, 1992; Goldman, 1993). As offspring encounter include opsonization of bacteria and infected cells,
new antigens, as many as 10 million different lympho- activation of the complement cascade and antibody-
cytes react to these antigens to cause subsequent dependent cellular cytotoxicity. Immunoglobulin
proliferation of particular lymphocytes lineages. The M activates the complement cascade and is the first
entire process of antigen recognition and lymphocyte antibody produced during a response. Immunoglobu-
activation and proliferation is known as “clonal selec- lin A protects mucosal surfaces from infection.
tion.” Clonal selection for lymphocytes is a process of Immunoglobulin E mediates allergic reactions (imme-
somatic evolution in which antigen receptor diversity diate-type hypersensitivity) and functions to clear
is maximized during a critical stage of development extracellular helminth infections. The functions of the
when offspring are continuously encountering new secreted form (nonmembrane bound) of IgD are not
infections. The process of clonal selection produces a yet known (Wallace Taylor, 2002).
diverse pool of lymphocytes with millions of different The variable region of the antibody, produced by
antigen-binding possibilities, all from simple progeni- four bounded polypeptide chains, confers high specifi-
tor cells (Burnet, 1959). Throughout this process, city for the target molecule, while the constant region
thymus volume regresses, lymphocytes diversify, and of the antibody binds the appropriate immune effector
immunoglobulin levels increase (Hannet et al., 1992; cells for activation. Genes for antigen-binding regions
George and Ritter, 1996). Despite this so-called thymic on lymphocytes as well as antibodies themselves are
involution, T cells still develop in this structure during randomly assorted from different gene segments or
adult life (Jamieson et al., 1999). clusters (variable [V], diversity [D], joining [J] and
constant [C]) on chromosomes 2, 14, and 22. This
Antibody-mediated immunity random process is also susceptible to splicing errors
B cells represent antibody-mediated (humoral) immu- and additional nucleotide insertions, and B cells can
nity. Antigen recognition by lymphocytes promotes undergo further receptor editing in their V gene in
cellular proliferation and the differentiation of B cells secondary lymphoid organs (Schatz et al., 1992; Radic
into plasma cells, which secrete antibodies or “immu- and Zouali, 1996). The results are millions of different
noglobulins,” and memory cells, which function in unique antibodies and antigen-binding sites on
immunosurveillance. B cells have the capacity to bind lymphocytes (Tonegawa, 1983). In fact, this rearrange-
“native” or free antigen. T cells, on the other hand, ment of mini-gene segments allows for much greater
recognize “processed” antigen. Receptors on antigen- diversity in antigen binding (estimated 1015 variable
presenting cells (including dendritic cells and B cells) regions on T and B cells) than there are genes in the
bind to antigens which are internalized, degraded, human body that could otherwise produce each indi-
and presented onto the cell surface via major vidual antibody.
histocompatibility complex (MHC; or human leuko-
cyte antigen, HLA) class I (HLA-A, B, and C) and II Cellular-mediated immunity
(HLA-DP, DQ, and DR) molecules. The MHC class I T cells represent cellular immunity, and different
molecules present their antigens to killer T cells (CD8), subsets are identified by their surface markers that
which initiate a cytotoxic response, whereas MHC regulate cellular activation and adhesion (CD number
class II molecules present their antigens to helper refers to “cluster of differentiation”). Cytotoxic T cells
T cells (CD4), which produce cytokines that facilitate (CD8) destroy infected host cells via perforin and lysis.
the clonal expansion of other T and B cells (Meyer and Cytotoxic T cells and natural killer cells are particularly
important for eliminating intracellular pathogens allergens and pathogens may predispose individuals to
(Berke, 1997). Suppressor T cells downregulate T-cell a dominant Th-2 response with high IgE levels and
responses after infection (see below). subsequent allergies and asthma later in life (the
Helper T cells (CD4) secrete cytokines and activate “hygiene hypothesis”) (Strachan, 1989; Cookson and
B cells to secrete antibodies. Cytokines are glycopro- Moffatt, 1997; Matricardi et al., 2000; Wills-Karp
teins that perform a variety of functions such as regu- et al., 2001; Yazdanbakhsh et al., 2002). Lack of per-
lation of cell growth and development (Snapper, 1996). sistent exposure to allergens and pathogens may not
Cytokines have several striking features; most import- allow for proper programming of an anti-inflammatory
antly, they perform pleiotropic actions and interact in regulatory response, such as IL-10 production (Wills-
different complex ways with each another. Cytokines Karp et al., 2001). In fact, nematode infection is asso-
have pleiotropic, redundant, and epistatic (synergistic ciated with fewer allergies and less asthma in some
and antagonistic) actions. That is, single cytokines can populations (Wilson and Maizels, 2004). Improve-
have multiple functions, multiple cytokines can have ments in sanitation may therefore explain the dispro-
similar functions, some cytokines work together to portionate increase in asthma morbidity and mortality
facilitate single functions, and some cytokines have over the past 25 years, despite improvements in
opposite functions to one another. There may even be medications (Von Mutius et al., 1992; Braun-Fahrlander
significant heritable variation in cytokine levels et al., 1999; Yazdanbakhsh et al., 2002). Clearly, early
(Williams-Blangero et al., 2004; Curran et al., 2005). life events produce various physiological effects in
CD4 helper T cells are generally differentiated into later adulthood (Barker et al., 2002; Barker, 2007).
two major subsets depending on the type of cytokine Childhood environments likely program the develop-
produced: type 1 (Th-1) and type 2 (Th-2) phenotypes ment of immune responses, and differences in local
(Mosmann et al., 1986; Mosmann and Coffman, disease exposure can explain differences in immune
1989a, 1989b; Mosmann, 1991a, 1991b; Coffman and development between populations (Mohammed et al.,
Mosmann, 1991; O’Garra 1998; Reiner and Seder, 1973; Lisse et al., 1997; McDade et al., 2004).
1999). Th-1 cytokines include, among others, inter- Other Th cell types include Th-17 cells that produce
feron-gamma (IFN-g), tumor necrosis factor-alpha IL-17, IL-6, and related cytokines, and Tregs, or induced
and -beta (TNF-a, -b), and various interleukins (IL-1b, regulatory T cells, that express Foxp3 (a forkhead
IL-2, IL-3, IL-12, etc.). These cytokines activate macro- winged-helix transcription factor). The absence of Tregs
phages, neutrophils and natural killer (NK) cells, medi- has been implicated in autoimmune diseases like inflam-
ate inflammatory responses and cellular immunity matory bowel disease (Shevach, 2008). The CD25þCD4þ
(T cells), promote cytotoxicity toward tumor cells, Tregs produce IL-10 and transforming growth factor
and enhance chemotaxis of leukocytes (Kobayashi beta (TGF-b) and are important for mucosal immunity
et al., 1989; Gazzinelli et al., 1993; Dinarello, 2000; (Kiyono et al., 2008). Th-3 (which produces high levels
Burger and Dayer, 2002; Trinchieri, 2003). of TGF-b), Tr1 and CD8þCD28 suppressor T cells are
The Th-2, anti-inflammatory cytokines include other subsets of suppressor T cells that may be different
many interleukins (IL-4, IL-5, IL-10, etc.) that induce from Tregs (Kiyono et al., 2008).
humoral immunity and antibody production (B cells),
eosinophil activation, mast cell degranulation, goblet
Comparative aspects
cell hyperplasia, mucin production, and intestinal mas-
tocytosis (resulting in histamine release). This cytokine Susceptibility to host infection depends on many
phenotype is important for protection against intes- factors, including whether or not the pathogen has
tinal infections as well as the facilitation of allergic been encountered before, inducing acquired immun-
reactions (Barrett et al., 1988; Rothwell, 1989; Cox ity. Nutritional status also plays an important role
and Liew, 1992; King and Nutman, 1992; Sher and since immune responses generate significant energetic
Coffman, 1992; Urban et al., 1992; Allen and Maizels, burdens (see below). Genetic predisposition also
1996; Else and Finkelman, 1998; Dinarello, 2000; accounts for differences in disease outcome in various
MacDonald et al., 2002). Despite the fact that Th-1 species. There is an incredible amount of polymorph-
and Th-2 cytokines act antagonistically to one another, ism in the genes that code for immune responses
both are usually present within the host at any given (Trowsdale and Parham, 2004). Several HLA alleles
time, although during infection one phenotype usually have been associated with resistance and susceptibility
predominates. to a variety of diseases, including malaria, tubercu-
Newborn humans tend to have a dominant Th-2 losis, and HIV (Hill, 1998). There is also population
phenotype, whereas the Th-1 phenotype develops later variation in the alleles that code for Toll-like receptors
with age (Jones et al., 2000). In the absence of a bal- on the surfaces of leukocytes that bind to antigens and
anced helper T cell phenotype, atopic disease can trigger important innate inflammatory responses
become more pronounced. Lack of early exposure to (Lazarus et al., 2002).
The Sm1 locus on chromosome 5 has been associated (Nonaka and Yoshizaki, 2004). However, adaptive
with susceptibility to Schistosoma mansoni in Brazil- immunity with the ability to generate diverse antigen
ian and Senegalese populations (Marquet et al., 1996), receptors on lymphocytes appears to have evolved only
and Sm2 on chromosome 6 has been associated with in vertebrates. The adaptive immune system in verte-
a high risk of liver fibrosis caused by S. mansoni in brates may have evolved in response to selection pres-
a Sudanese population (Dessein et al., 1999). These sures by diverse parasitic flatworms, viruses, and
alleles likely cause dysfunctions in cytokine and bacteria as well as longer life spans, higher metabolic
lymphocyte proliferation responses to infection rates, and bigger genomes in the vertebrate hosts (Rolff,
(Rodrigues et al., 1999). Research also suggests signifi- 2007). A more complex immune response may also have
cant heritable variation in hookworm infection inten- been helpful in differentiating potential pathogens from
sity in a Zimbabwe population (Williams-Blangero symbiotic microflora (Pancer and Cooper, 2006).
et al., 1997) as well as heritable variation in Ascaris Within vertebrates, the process of producing the
lumbricoides and Trichuris trichiura infection inten- lymphocyte receptor repertoire is different in the jawed
sities in a Nepalese population (Williams-Blangero gnathostomes compared to the jawless agnathans,
et al., 1999, 2002a). Several loci on chromosomes 1, 8, with conventional rearrangeable immunoglobulin
9, 11, 12, 13, and 18 may alter cytokine and immuno- gene segments in the former and rearrangement of
globulin responses to these infection, resulting in leucine-rich repeat-encoding modules in the latter
heritable variation in immune responses in these popu- (Flajnik and Kasahara, 2001; Pancer et al., 2004; Alder
lations (Williams-Blangero et al., 2002b, 2008a, 2008b). et al., 2005; Cooper and Alder, 2006; Pancer and
While there are certainly important genetic compon- Cooper, 2006). Jawed vertebrates adapting a predatory
ents to variation in immune responses, even adaptive lifestyle may have needed more complex and robust
ones, to human pathogens, the utility of heritability immune responses, particularly in their gastrointest-
estimates obtained from studies not using monozygo- inal tracts (Matsunaga and Rhaman, 1998). In these
tic twins is equivocal (Vitzthum, 2003). Several studies jawed vertebrates, the adaptive immune responses
have reported no significant heritable variation in sus- likely evolved when a transposable element (mobile
ceptibility to Schistosoma haematobium in a Kenyan DNA) produced an immunoglobulin-like gene (RAGs,
population (King et al., 2004) or in infection intensity recombination activating genes). The transposon
from Strongyloides fuelleborni in a population of Papua inserted itself into an Ig superfamily (IgSF) gene of
New Guinea (Smith et al., 1991). the variable (V) type, leaving behind the machinery
Despite these disagreements, it is well accepted that for the original receptor gene to cut and past independ-
all organisms (examined to date) have some immune ent loci which allowed for somatic gene rearrangement
responses, including phagocytic abilities and the abil- for the various V(D)J mini-gene combinations (Agra-
ity to recognize self from nonself. Notwithstanding wal et al., 1998; Fugmann et al., 2000). The results are
these similarities, there is extraordinary variation in the production of highly polymorphic combinations of
the immune responses within the Animal Kingdom a/b- and g/d-chains of T-cell antigen receptors and the
(Flajnik and du Pasquier, 2004). Invertebrate immun- heavy/light chains of immunoglobulin B-cell receptors.
ity closely resembles innate immunity in vertebrates This mechanism is estimated to have evolved more
(Hoffmann and Reichhart, 2002). Phagocytic cells cir- than 500 million years ago (Flajnik, 2002).
culate in the hemolymph and encapsulate pathogens. Immune responses within all jawed vertebrates
Lectins opsonize foreign antigens and interference appear to be rather conserved, with significant homo-
RNA (RNAi) inhibits viral gene function. Proteins, such geneity in the defense mechanisms of different species
as fibrinogen-related proteins (FREPs) in the snail (Marchalonis and Schluter, 1994; Litman et al., 2005).
Biomphalaria glabrata and the products of Down’s syn- In fact, there are very few biochemical and genetic
drome cell-adhesions molecule (DSCAM) genes in differences in the immune systems of humans and
Drosophila melanogaster, bind invading molecules common chimpanzees (Muchmore, 2001). This is in
(Adema et al., 1997; Yu and Kanost, 2002; Meister, spite of the fact that chimpanzees are less susceptible
2004; Loker et al., 2004). to some infections, like immunodeficiency virus, and
Plants exhibit hypersensitivity responses that cause more susceptible to others, like pneumonia. The com-
cellular apoptosis and exhibit characteristics of local- parative study of primate immunology will prove quite
ized and systemic acquired resistance via antimicro- insightful for human evolutionary biologists.
bial peptides and pathogen-associated molecular
patterns (PAMPs) (Dangl and Jones, 2001; Innes, 2004;
Evolutionary and ecological immunology
Chisholm et al., 2006). Some aspects of the complement
system (like the C3 component) are shared between Research on immunological stress has traditionally
vertebrates, invertebrate deuterostomes (e.g., sea focused primarily on understanding somatic mainten-
urchins), and even some protostomes (e.g., nematodes) ance, repair, and defense against pathogens. From an
evolutionary perspective, immune functions are critical (Rosenberg and Bowman, 1984; Hadju et al., 1995;
for maximizing survivorship, and an optimized imm- Kramer et al., 1997; Klasing, 1998; Shephard et al.,
une system should always be highly selected for. 1998; Lin et al., 1998; Koski et al., 1999; Ing et al.,
Immune functions have therefore played important 2000). In turn, acute infection in adult humans can
roles in the evolution of organismal life histories. Life cause high amount of protein loss, greater than 1 g/kg
history strategies are complex adaptations for survival of body weight per day (Scrimshaw, 1992). Strenuous
and reproduction via the co-ordinated evolution of exercise or participation in energetically demanding
somatic and reproductive developmental processes tasks, such as migration, breeding, or molting, can also
(Stearns, 1992). There exists an enormous amount compromise immune functions (Nelson et al., 2002).
of variation in organismal life history strategies, For example, increased brood size is associated with
and much of the physiological variation between and reduced antibody response against Newcastle disease
within organisms can be explained using several con- virus and increased Haemoproteus infection intensity
cepts of life history theory, most notably trade-offs in collared flycatchers (Ficedula albicollis) (Nordling
and reaction norms (Stearns, 1992; Ricklefs and et al., 1998), reduced antibody response against sheep
Wikelski, 2002). red blood cells in zebra finches (Taeniopygia guttata)
(Deerenberg et al., 1997) and female tree swallows
Immunity as an evolved reaction norm (Tachycineta bicolor) (Ardia et al., 2003), and increased
Both somatic and reproductive physiologies are prevalence of Plasmodium in male great tits (Parus
evolved response systems, shaped by natural and major) (Richner et al., 1995).
sexual selections to adapt individuals to changing Metabolic rate, oxygen consumption and thermo-
environments. This allows for a variable physiological genic activity also frequently increase following
response (a “reaction norm”) in which a genotype can immune stimulation (Newsholme and Newsholme,
produce a range of phenotypes (through short-term 1989; Spurlock, 1997; Lockmiller and Deerenberg,
changes, such as acclimatization to altitude, and 2000). For example, house mice (Mus musculus)
long-term adaptations) depending on environmental injected with the antigen keyhole limpet hemocyanin
conditions. However, this phenotypic plasticity is show a 20–30% increase in oxygen consumption
limited through lineage-specific effects (or the canal- (Demas et al., 1997). Likewise, blue tits (Parus caeru-
ization of certain traits) as well as trade-offs. Assuming leus) immunized with diptheria-tetanus vaccine
a limited supply of energy and time, organisms are exhibit an 8–13% increase in resting metabolic rate
required to allocate physiological resources between a (Svensson et al., 1998), and great tits (Parus major)
number of competing functions, particularly reproduc- and collared doves (Streptopelia decaocto) injected with
tion, maintenance (i.e., survival) and growth (Stearns, sheep red blood cells exhibit a 9% increase in resting
1989). Organisms will therefore be under selection to metabolic rate (Ots et al., 2001; Eraud et al., 2005). In
develop and maintain physiological systems that allow humans, fever typically results in a 7–15% increase in
for the efficient regulation of resources between these resting metabolic rate for every 1 C rise in body tem-
functions. In a stochastic environment, those organ- perature (Barr et al., 1922; Roe and Kinney, 1965; Elia,
isms that can most efficiently regulate the allocation 1992). In a population of 25 adult male college students
of resources between competing traits will likely sampled during and after acute upper respiratory tract
exhibit increased lifetime reproductive success. infection, resting metabolic rate was, on average, 8%
An individual’s immune system is an excellent higher during infection compared to samples taken
example of a reaction norm that allows for short- and after complete recovery (Muehlenbein, 2008b). It is
long-term phenotypic plasticity in response to environ- interesting that these metabolic values were elevated
mental signals such as pathogens, allergens, and even in the absence of fever, likely reflecting increased
injury. Immunocompetence, or the ability to mount energetic demands despite mild infection. Further
an effective immune response, is an integral compon- research should investigate changes in metabolic rates
ent of organismal life histories precisely because: (1) it of adult humans during illnesses of varying severities
is crucial for maximizing evolutionary fitness; and and in individuals with different states of energy
(2) it is energetically expensive to produce, maintain, balance.
and activate. This important function can be character-
ized as an energetic burden subject to allocation mech- Trade-offs with immunity
anisms (Sheldon and Verhulst, 1996; Demas et al., 1997; “Every trait must be analyzed in terms of the costs and
Raberg et al., 1998, 2002; Verhulst et al., 1999; benefits of the trade-offs in which it is involved”
Owens, 2002; Schmid-Hempel, 2003; Muehlenbein and (Stearns et al., 2008, p. 11). As immune responses are
Bribiescas, 2005; Muehlenbein, 2008a). For example, energetically expensive, optimized immune functions
prolonged energy restriction can lead to immune sup- should trade-off with other critical life history func-
pression in humans and nonhuman animals alike tions, like growth. Nutrient deficiencies can have
significant, long-term negative effects on the human captive male macaques (Macaca fasicularis) is associ-
immune system (Lunn, 1991; Gershwin et al., 2000), ated with significant declines in serum testosterone
and these effects may begin early in life. For example, levels (Muehlenbein et al., 2006). Hypogonadism has
infants in the Philippines born small-for-gestational also been reported in association with African sleeping
age exhibit slower growth rates and produce less thy- sickness (Trypanosoma brucei) (Reincke et al., 1998),
mopoietin as adolescents (McDade et al., 2001b). These toxoplasmosis (Toxoplasma gondii) (Oktenli et al.,
individuals are also less likely to produce antibodies in 2004), schistosomiasis (Schistosoma mansoni) (Saad
response to typhoid vaccination (McDade et al., 2001a). et al., 1999), and filarial infection (Loa loa and Manso-
Elevated concentrations of a-1 antichymotrypsin (an nella perstans) (Landsoud-Soukate et al., 1989).
acute phase protein produced by the liver during Changes in testosterone levels throughout the range
inflammation) are also associated with growth faltering of physiological variation may function as a basic
(lower height-for-age) in Nepalese adolescents (Panter- aspect of male phenotypic plasticity and an adaptive
Brick et al., 2000). Activation of proinflammatory response that facilitates the allocation of metabolic
immune responses (as in the case of inflammatory resources according to available energy and disease
bowel disease) is associated with delayed puberty in risk in a stochastic environment. Assuming testoster-
even adequately nourished individuals (Ballinger one’s immunomodulatory actions are primarily sup-
et al., 2003), and elevated C-reactive protein levels are pressive (for review see Muehlenbein and Bribiescas,
associated with reduced gains in height across three 2005), depressed testosterone levels during illness or
months in Tsimane children of Amazonian Bolivia injury could function to prevent immunosuppression
(McDade et al., 2008). Continued work on comparative by otherwise higher testosterone levels (Wedekind
developmental immunology within and between and Folstad, 1994). In addition, depressed testoster-
populations will prove interesting. This will include one levels could function to limit metabolic invest-
continued efforts to qualify and quantify trade-offs ment in energetically expensive anabolic functions
between immunity and reproductive effort. (Muehlenbein, 2008a).
Optimization of reproductive effort is of central Testosterone increases energetic costs through
importance, especially for capital breeding, iteropar- direct actions on muscle tissue and metabolism
ous organisms that must budget time and stored (Welle et al., 1992; Bhasin et al., 1996), and this may
energy over a number of reproductive events within decrease survivorship in resource-limited environ-
a lifetime. Under conditions of resource restriction, a ments (Ketterson et al., 1992; Bribiescas, 2001). The
trade-off between current and future reproduction is problem would become exacerbated in pathogen-rich
predicted: investments in current reproductive events environments because of the immunosuppressive
may negatively affect future reproductive returns (the actions of testosterone and because investment in
“cost of reproduction” argument). Investments in muscle anabolism generates a significant energetic
reproduction should also compromise survivorship demand that will theoretically trade-off with the com-
through depressed immune functions. Conversely, peting energetic demands of immunocompetence. An
investment in immune activation should compromise evolutionary and ecological perspective on immunity
reproductive effort. In mosquitoes (Anopheles gam- would suggest that natural and sexual selections favor
biae), injection with lipopolysaccharide is associated individuals that can best balance the trade-offs so as to
with reduced egg production (Ahmed and Hurd, maximize reproductive effort and survivorship (i.e.,
2006). Deerenberg et al. (1997) have shown that only immunity) given different ecological conditions. In
47% of breeding zebra finches (Taeniopygia guttata) lower pathogen-risk environments (e.g., higher lati-
produced antibodies in response to infection with tudes), less of a premium may be placed on immunity,
sheep red blood cells whereas all nonbreeding birds and it may pay to select for less robust immune
produced antibodies. responses (Muehlenbein, 2008a).
In humans, hypogonadism (decreased levels of hor-
mones from the testes or ovaries) and hypogonadotrop- Immunity and mate choice
ism (decreased levels of gonadotropins from the It is also predicted that individuals should develop
hypothalamus and pituitary glands) are common honest signals of survivorship (i.e., immunocompe-
physiological responses to somatic injury. For example, tence) in an effort to maximize mate choice (Zahavi,
in men, serum testosterone decreases during sepsis, 1975; Hamilton and Zuk, 1982). Animals should be
burns, myocardial infarction, and surgery (Spratt under selective pressure to evolve preferences for those
et al., 1993; Spratt, 2001). Honduran men infected mates that possess reliable indicators of pathogen
with Plasmodium vivax exhibit significantly lower tes- resistance by scrutinizing characteristics that honestly
tosterone levels than age-matched healthy controls reflect health or the ability to resist pathogens.
(Muehlenbein et al., 2005). Similarly, experimental A number of morphological and behavioral char-
Venezuelan Equine Encephalitis virus infection in acteristics appear to be honest sexual signals of
immunocompetence in avian and other species. For (1632–1723), Ignaz Philipp Semmelweis (1818–1865),
example, tail length was positively associated with and John Snow (1813–1858) (see Kiple, 1993, 2003;
cell-mediated immune function in male barn swallows Porter, 2001, 2006). The actual germ theory of disease
(Hirundo rustica) (Saino et al., 2002). Male barn swal- is attributed to Agostino Bassi (1773–1856) and Louis
lows with longer outermost tail feathers also exhibited Pasteur (1822–1895) (see Kiple, 1993, 2003; Porter,
stronger primary antibody responses following an 2001, 2006). Pasteur demonstrated that microorgan-
immunization (Saino et al., 2003b), had higher testos- isms do not arise spontaneously, but are the products
terone levels (Saino and Moller, 1994), and were pre- of reproduction by existing microorganisms. Around
ferred by females, both as social mates and extrapair the same time, Heinrich Hermann Robert Koch
copulation partners (Saino et al., 1999). Fluctuating (1843–1910), along with his mentor Friedrich Gustav
asymmetry of antlers in male reindeer (Rangifer taran- Jakob Henle (1809–1885) and associate Friedrich
dus) was associated with immune parameters during August Johannes Loeffler (1852–1915), provided the
the rut, suggesting that low fluctuating asymmetry in scientific community with the “postulates” or experi-
sexually selected ornaments may also signal the ability mental criteria to establish a causal relationship
to resist parasites (Lagesen and Folstad, 1998). between these microorganisms and disease (see Kiple,
Some primates may exhibit signals that honestly 1993, 2003; Porter, 2001, 2006). In brief, the agent or
indicate health and survivability, such as coloration microorganism must be found in all cases of the dis-
in the facial, scrotal, and perianal regions. Examples eased, but not healthy, hosts. The organism must be
may include sexual colorations in adult male vervet isolated from diseased hosts and cultured. Inoculation
monkeys (Cercopithecus aethiops sabaeus) (Gerald, of the culture into susceptible, healthy hosts must
2001) and mandrills (Mandrillus sphinx) (Setchell and reproduce the disease, and the agent must be reisolated
Dixson, 2001). However, there have been no published from the newly infected host. This form of deductive
studies to date that have investigated relationships reasoning, although criticized by many, uses observ-
between immunocompetence and degree of sexual col- able, empirical evidence to test hypotheses about the
oration in primates. For humans, muscle mass may be cause of infectious disease.
an honest indicator of survivorship due to the signifi- Infectious organisms include thousands of species
cant costs of anabolic steroids, including increased of viruses (and bacteriophages), bacteria (including
energetic costs and the risk of negative energy balance, rickettsiae), parasitic protozoa and helminthes (nema-
increased risk of prostate cancer, production of oxygen todes, cestodes, and trematodes), and fungi. These
radicals, increased risk of injury due to hormonally parasitic organisms live all or part of their lives in or
augmented behaviors such as aggression, violence, on a host from which biological necessities are derived.
and risk taking, reduced tissue (especially adipose) This state of metabolic dependence usually results in
and organ maintenance, and suppression of immune host energy loss, lowered survival, and reduced repro-
functions (Muehlenbein and Bribiescas, 2005; ductive potential. Disease or illness is the impairment
Muehlenbein 2008a). It may also be the case that of host body function done by a pathogen.
morphological symmetry is a potential indicator of There is fantastic variation in the transmission
immunological status in humans. Morphologically dynamics of infectious (communicable) organisms
symmetric humans are frequently judged as more (Anderson and May, 1992; Combes, 2004; Poulin,
attractive and are preferred as potential mates 2006). The primary infection transmission routes
(Grammer and Thornhill, 1994; Gangestad and Thorn- include fecal-oral (ingestion of contaminated food,
hill, 1998; Perrett et al., 1998). More research should water, or other objects), respiratory, vector-borne
clearly be conducted with humans in this area, particu- (e.g., mosquitoes, ticks, flies, etc.), blood-borne, sexu-
larly given the interesting sexual selection behaviors ally transmitted, vertical transmission (congenital;
that humans use and the myriad of pathogens that mother to offspring), and nosocomial (hospital-
can infect us. acquired). Zoonotic infections are those acquired from
nonhuman animals. A reservoir is the biotic or abiotic
source where a pathogen normally lives and repro-
INFECTIOUS DISEASE duces. Latency is the period of inactivity of the patho-
gen inside the host, or the period between initial host
The initial description that diseases have natural rather infection and the subsequent ability of the infected
than supernatural causes is attributed to Hippocrates host to infect new hosts. The incubation period is the
of Cos (460–370 BC). However, several others further interval between initial infection and onset of clinical
developed the concept of “contagion,” including illness (with signs and symptoms). This period can
Marcus Terentius Varro (116–27 BC), Abū Alı̄ ibn vary depending on dose of exposure, host susceptibil-
Sı̄na (980–1037), Girolamo Fracastoro (1478–1553) ity, pathogenicity of the infectious agent, and other
Francesco Redi (1626–1697), Anton van Leeuwenhoek factors. A carrier is an infected host that does not
present any signs or symptoms of infection, but is still bacteria or transduction from bacteriophages, sexual
capable of infecting other hosts. reproduction in malaria, etc.). Coevolution of organ-
Epidemiology is the study of the distribution (fre- isms, and the conflict that often ensues, provides sig-
quency and pattern) and determinants (etiology) of nificant selection pressure for the evolution of traits,
health-related events within populations. Endemic dis- and understanding this can assist in the explanation of
eases are those that occur regularly at low to moderate health-related traits. Understanding the conflicts
frequency, epidemics are outbreaks that occur above between hosts and pathogens can aid in our under-
endemic levels, and pandemics are epidemics that standing of why antibiotic resistance evolves and why
affect a large proportion of the world’s population. some diseases are very deadly and others less so.
Specifics of transmission dynamics, epidemiologic
study designs, and how health-related conditions are
Virulence and antibiotic resistance
specifically associated with exposures will not be dis-
cussed here (see Sattenspiel, 2000, for an introduction The traditional view of host–pathogen coevolution sug-
to epidemiologic study designs). gested that evolutionary processes should theoretically
lead to reduced antagonism or symbiosis since this
would be in the best interest for both the pathogen
Coevolution
and host (Smith, 1934; Swellengrebel, 1940; Allee
Infectious organisms offer a near-ubiquitous selective et al., 1949). Longer coexistence between hosts and
evolutionary force (Levin, 1996). Many of these patho- pathogens would theoretically lead to attenuated infec-
gens have infected humans and our hominin ancestors tions (Burnet and White, 1972). This “group selection-
for a large part of our evolutionary history (Hoberg ist” reasoning implies some type of co-operation
et al., 2001; Goncalves et al., 2003; Van Blerkom, between hosts and parasites. However, a more modern
2003). For example, hominins have certainly been view is that natural selection will favor the increase of
infected with herpesviruses for millions of years fitness in both hosts and parasites, which may not lead
(Sharp et al., 2008). Helicobacter pylori has likely to obligate evolution towards benign interactions.
infected humans for as much as 60 000 years (Linz Virulent pathogens are characterized by high levels
et al., 2007), and Salmonella typhi, the causative agent of host exploitation, producing high morbidity and
of typhoid fever, has likely affected humans for 30 000 mortality. Virulence can evolve when the benefits of
years (Roumagnac et al., 2006). host exploitation are outweighed by the costs to the
Conflict between organisms is ubiquitous, even pathogen from host damage (Galvani, 2003). High
between parents and offspring (Trivers, 1974; Haig, virulence is more common when host immobility does
1993). Just as predators and prey coevolve in an escal- not disrupt pathogen transfer. Examples include
ating cycle of complexity with predators’ improved vector-borne, water-borne, and nosocomial infections
hunting techniques countered by prey’s improved in which intense host exploitation comes at little cost
armor or defensive adaptations, hosts and parasites to the pathogen because it is not dependent on host
must evolve in order to maintain current levels of adap- mobility for transmission to new hosts (Ewald, 1996).
tation (Dawkins and Krebs, 1978). Hosts and patho- Such is the case for malaria and cholera. Infectious
gens coevolve together in a constant state of flux, with organisms that can survive in the external environment
reciprocal modification of evolutionary strategies pro- for lengthy periods of time also often evolve high levels
ducing evolutionary change in host traits in response of virulence, as is the case of anthrax (Walther and
to evolutionary change in pathogen traits, and vice Ewald, 2004). Vertical transmission (mother to off-
versa (Thompson, 1994). The result is oscillations in spring) is more often associated with less virulent infec-
levels of host resistance and pathogen invasiveness, tions because the well-being of both the host and parasite
and a subsequent arms race of specializations over time. are linked (Bull et al., 1991; Messenger et al., 1999).
The struggle for existence does not get easier, not New, accidental infections in dead-end hosts may
matter how well a species may adapt to its current result in high virulence, as in the case of rabies (Ebert
environment because competitors and enemies are and Bull, 2008). Colonization of a new host population
also adjusting, causing significant change in the adap- following successful host switching may also be asso-
tive landscape (the “Red Queen hypothesis,” Van ciated with initial increases in virulence. Level of
Valen, 1973). Sexual reproduction may have evolved pathogen virulence may also be a function of host
specifically as a mechanism to combat against high recovery rate, the geographic and temporal distribu-
pathogen evolutionary rates and infectious disease tion of the host population, and even host age (Koella
potential (Howard and Lively, 1994). However, host and Turner, 2008). Pathogen–pathogen competition
recombination is often met with genetic recombin- over host resources also plays an important role
ation in pathogens (e.g., recombination and mutation, (Nowak and May, 1994). Within the host, pathogens
lateral gene combination via conjugation between must evolve strategies to either coexist or outcompete
27.2. Modes of antibiotic resistance. Bacteria can ‘eject’

(a), degrade (b), or even inactivate (c) antibiotics. Figure
Antibiotic-
resistance Antibiotic- reprinted with permission from Laurie Grace.
genes efflux pump
Antibiotic-
degrading
enzyme a
b
Antibiotic
c
Plasmid
Antibiotic
Antibiotic-
Bacterial altering
enzyme Antibiotic
cell
Chromosome
other members of its own or separate species (Kim, High pathogen variability within hosts can also
1985). If within-host genetic relatedness of such patho- contribute to antibiotic resistance. Antibiotics are che-
gens is great, the likelihood of evolution towards aviru- motherapeutic substances that kill or inhibit bacterial
lence is increased as these pathogens should tend to growth by disrupting cell wall, nucleic acid and protein
“co-operate” with each other, analogous to “kin selec- synthesis, and altering metabolic pathways and cell
tion.” Alternatively, high within-host genetic related- membrane integrity (Levy, 1998). Broad-spectrum
ness of pathogens may lead to increased virulence via antibiotics, like tetracyclines, are useful in controlling
kin selection if the benefits associated with increased several types of bacteria, like chlamydias, rickettsias,
virulence are shared across the pathogen population gram-positive and gram-negative bacteria. They are
(Ewald and Cochran, 2004). often used before the pathogens are identified or anti-
In contrast, high within-host genetic variability biotic susceptibility has been tested for. However, they
could favor increased competition with an escalation are also more likely to negatively affect normal flora in
towards high virulence. A more exploitive variant of a the body.
pathogen may be more successful at reproduction, Pathogens previously susceptible to antimicrobials
further increasing within-host pathogen genetic vari- are becoming increasingly resistant. The antibacterial
ability and favoring parasite–parasite competition effects of penicillin, a b-lactam derived from Penicil-
(between different strains or species) and increased lium mold, were described by John Tyndall (1820–
virulence. One example is the high virulent outcomes 1893), Ernest Duchesne (1874–1912), Clodomiro
during coinfection with multiple malaria strains Picado Twight (1887–1944), and Alexander Fleming
(Conway et al., 1991). (1881–1955). Within a very short time of penicillin’s
Imperfect vaccines designed to limit pathogen mass production and clinical use, resistant strains of
growth and toxicity could contribute to increased Staphylococcus aureus were identified (Spink and
pathogen virulence (Gandon et al., 2001; Mackinnon Ferris, 1945). Now over half of all such strains are
et al., 2008). A host population imperfectly protected resistant to penicillin and its derivatives (Chambers,
against morbidity and mortality could generate selec- 1997). Microbes are accomplishing resistance by
tion pressure for the evolution of more virulent blocking entry of antimicrobials into cells or removing
organisms. Such strains could develop to increase (drug efflux), degrading or otherwise altering the anti-
competitive advantage over other strains during coin- microbials (Figure 27.2). This does occur naturally, but
fection as well as increase the likelihood of successful humans have facilitated these processes by inappropri-
transmission, assuming transmission is still possible ate use of antimicrobials through self-medication, lack
from vaccinated hosts. This would place the unvaccin- of patient compliance (i.e., premature termination of
ated host population at increased risk of death and treatments), demands on physicians to over-prescribe,
disability from the new dangerous strains. and overuse in livestock (Austin et al., 1999). Millions
of kilograms of antibiotics are produced per year, and worldwide prevalence (number of total cases) as great
the majority of them are used in livestock (Mellon as two billion people, resulting in as many as three
et al., 2001). million human fatalities annually (Bloom and Murray,
Random mutations, recombination, reassortment, 1992). The highest incidence (number of new cases
and lateral gene transfer (including transduction from within a given time period) of tuberculosis are pres-
bacteriophages, uptake of naked DNA and transpo- ently in India, China, Indonesia, Bangladesh, Pakistan,
sons, and conjugation or plasmid exchange between and several countries in Africa (Dye et al., 1999). Use
bacteria) can all produce resistant microbes (Levy, of the Bacille Calmette-Guérin (BCG) vaccine is
1998; Lipsitch, 2001; Levy and Marshall, 2004). The widespread, but of limited efficacy in adults (Ellner,
selection pressures we impose on them provides ample 1997). Rifamycin-, isoniazid- and multidrug-resistant
impetus for rapid evolution and proliferation of resist- strains have evolved and spread rapidly (Drobniewski
ant species. Fortunately not all pathogen populations et al., 2002).
develop resistance because resistant bacteria appear to Tuberculosis infection is spread via the inhalation
compete poorly against sensitive bacteria in the of infected respiratory secretions. Macrophages
absence of antibiotics, possibly because of energetic attempt to phagocytose, and then kill via reactive
costs associated with carrying nonessential plasmids oxygen and nitrogen intermediates, the tubercle bacilli
(Courvalin, 2008). Future chemotherapeutic agents following inhalation. Those mycobacteria which
will benefit from directing actions towards virulent escape this destruction will trigger a proinflammatory
pathogens, making them less competitive against cellular immune response (effector T cells with subse-
benign counterparts. Simultaneous treatment with quent production of proinflammatory cytokines, like
several different antibiotics also creates a more hetero- TNF-a, IL-12, and IFN-g), which are vital for control-
geneous environment for bacterial populations to over- ling infection (Lenzini et al., 1977; Havlir et al., 1991;
come (Bergstrom et al., 2004). Ellner, 1997; van Crevel et al., 2002). The active form
of vitamin D (1,25 dihydrocholecalciferol) impairs
growth of M. tuberculosis inside activated macro-
Case studies in human evolutionary biology
phages (Rook, 1988). Vitamin D deficiency, even due
I conclude this chapter with detailed accounts from to seasonal variation in food resources, may therefore
three of the most notable bacterial, viral, and proto- increase the risk of disease from tuberculosis (Douglas
zoan pathogens in humans: tuberculosis, human et al., 1996; Wilkinson et al., 2000).
immunodeficiency virus (HIV), and malaria. Each has In most people, infection becomes stabilized as a
its own unique evolutionary history and all offer solid fibrous granuloma inhibits further growth of the
insight into human–pathogen coevolution. Finally, pathogen. However, diminished Th-1 proinflammatory
emerging infectious diseases, their causes, and conse- cytokine responses, caused in part by the overproduc-
quences are considered so as to illustrate the import- tion of TGF-b (Toossi et al., 1995), can result in hema-
ance of identifying cultural as well as biological togenous dissemination and spread of infection
adaptations against human disease. throughout the lungs and other tissues (van Crevel
et al., 2002). Slow progression of disease is an excellent
Tuberculosis mechanism by which the likelihood of transmission to
Tuberculosis is caused by one of several bacteria of the susceptible hosts is increased. The mycobacteria can
genus Mycobacterium. These gram-positive bacteria exist within the phagosomes of macrophages in human
are aerobic, nonmotile, and posses a thick hydrophobic lungs for years.
cell wall. The Mycobacterium “complex” includes People can exhibit a wide spectrum of immune
M. tuberculosis, M. africanum and M. canettii of humans, responses to tuberculosis infection (Lenzini et al.,
M. microti of rodents, M. caprae of various mammals 1977), and not surprisingly resistance and susceptibil-
(including humans), M. pinnipedii of seals, and M. bovis ity to infection has been associated with some genetic
of bovine and many other mammalian species. Many polymorphisms, particularly in the human leukocyte
other atypical species are found in soil, water, and other antigens that present mycobacterial proteins to effector
animals (from fish to birds to monkeys), and several of cells (Goldfeld et al., 1998). The HLA-DQB1*0503 allele
these species can cause disease in humans, particularly is significantly associated with susceptibility to clinical
in immunocompromised individuals. The causative tuberculosis (Goldfeld et al., 1998) as are members of
agent of leprosy (Mycobacterium leprae) naturally infects the HLA-DR2 serotype (Bothamley et al., 1989; Brahma-
humans, chimpanzees, armadillos, and several species of jothi et al., 1991; Rani et al., 1993). Variants of the solute
monkeys, but is only distantly genetically related to carrier family 11, member 1 gene (NRAMP1) have been
tuberculosis (Grosskinsky et al., 1989). associated with susceptibility to tuberculosis in a var-
Mycobacterium tuberculosis is one of the most iety of human populations, including Japanese and
ubiquitous pathogens in humans, with an estimated West Africans (Bellamy et al., 1998; Gao et al., 2000).
Mutations in the Toll-interleukin-1 receptor domain

and Toll-like receptor-2 genes are also associated with
sever disease outcome (Hawn et al., 2006; Thuong et al.,
2007). A single-point mutation in IFN-g receptor 1 gene
is also associated with progressive infection due to
downregulated cell-mediated inflammatory responses
(Newport et al., 1996). There may be other genetic
variants that affect susceptibility and resistance to
tuberculosis.
Mycobacteria have certainly been infecting human
populations for a long time. The last common ancestor
of all mycobacteria is estimated at 2.6–2.8 million years
before present (Gutierrez et al. 2005). As there is rela-
tively low variation in the housekeeping genes within
M. tuberculosis, Sreevatsan et al. (1997) have con-
cluded that the organism experienced an evolutionary
bottleneck around 15 000–20 000 years before present.
More sensitive analyses revealed genetic variation that
allowed others to conclude that the M. africanum,
M. microti, and M. bovis lineages likely diverged from
the M. tuberculosis ancestor, not that M. tuberculosis
evolved from M. bovis (Brosch et al., 2002). Mycobac-
terium bovis was long considered ancestral to M. tuber-
culosis because the former has a wide range of hosts,
whereas the latter is human-specific (Cole et al., 1998).
Genetic analyses now confirms the opposite, that
M. tuberculosis is likely ancestral to the other members
of the Mycobacterium complex. This complex was likely
African in origin, and the youngest strains causing 27.3. A Pre-Columbian human specimen infected with tubercu-
modern endemic human tuberculosis were introduced losis. The photograph shows a fused lumbar spine and sacrum
into the various geographic regions. Mycobacterium from a 19–22-year-old human female recovered from the Middle
Mississippian Schild Cemetery, Greene County, Illinois, excav-
bovis is actually the youngest of the complex species
ated by Gregory Perino in 1962. The specimen dates to 1020 AD
(Smith et al., 2006). (110 years) and is genetically diagnosed with Mycobacterium
Although many have argued against a bovine origin tuberculosis (Braun et al. 1998). Photograph courtesy of Della
for M. tuberculosis (Mostowy et al., 2002), 20 000 years Cook.
may not have been enough time for the diverse strains
to develop in their respective hosts (Brosch et al.,
2002). Others estimate the most recent last common geographically distinct. There is strong evidence for
ancestor of the complex at around 35 000 years before phylogeographic relationships between these different
present (Hughes et al., 2002). Mycobacterium canettii strains and their human hosts. For example, East Asian
may have even diverged before this bottleneck individuals seem to be more susceptible to East
(Gutierrez et al., 2005). Also prior to the bottleneck of Asian strains of the mycobacteria, even if the infection
the complex members, M. tuberculosis likely acquired is acquired outside of East Asia, suggesting some coe-
several virulence genes (e.g., Rv0986–8 that inhibit volution of the parasites with the hosts (Gagneux et al.,
macrophage functions) via horizontal transfer of a 2006).
plasmid from a gammaproteobacterium donor species,
like Agrobacterium (Rosas-Magallanes et al., 2006). Human immunodeficiency virus
Several other virulence genes have now been identified Human immunodeficiency virus (HIV) is a double-
in M. tuberculosis (Ernst et al., 2007). stranded RNA virus of the family Retroviridae, subfam-
Tuberculosis certainly infected humans in North ily Lentivirus (see Hutchinson, 2001, and Rambaut
America prior to European contact (Braun et al., et al., 2004, for review). Type 1 HIV (HIV-1) includes
1998) (Figure 27.3). Mycobacterium tuberculosis was groups N and O, found primarily in Gabon and Camer-
present in North American bovids, including bison, oon, and the pandemic group M, for which there are
bighorn sheep, and musk ox, at least 17 000 years eleven different subtypes or viral clusters (A–K). There
before present (Rothschild et al., 2001). Presently, are eight subtypes (A–H) of HIV-2 which are mostly
the various strains of M. tuberculosis are rather found in West Africa and India. Infection by HIV-2 is
characterized by much slower disease progression

compared to HIV-1 (Marlink et al., 1994).
Transmission of HIV is through fluid exchange,
primarily sexual contact, inoculation with blood or
blood products, and perinatal transmission. Upon
entry into the body, HIV’s envelope protein (gp120)
binds to CD4 and chemokine coreceptors (e.g., CCR5
and CXCR4) on the surface of helper T cells. The virus
fuses to the host cell surface and inserts its viral core.
The viral genome is reverse transcribed and integrated
into the host genomic DNA. Viral RNA is then tran-
scribed, viral proteins are translated, viruses are
assembled and bud from the infected cell (Rambaut
et al., 2004). Due to the imperfect reverse transcription
process, many errors accumulate, resulting in a mas-
sive amount of HIV genetic diversity in a host at any 27.4. Chimpanzees are often used for bushmeat. Photograph
courtesy of David Watts.
given time (Rodrigo, 1999).
Initial infection is followed by high viral replication
and mild, ‘flu-like illness followed by an asymptomatic The source of HIV was not biological warfare or divine
period of approximately 10 years. During this time, the retribution against this community. Rather, HIV ori-
virus typically exhibits low replication rates and is ginated from nonhuman primate simian immunodefi-
often sequestered out of peripheral circulation and into ciency viruses (SIV). Based on overwhelming genetic
gut-associated lymphoid tissue (Chun et al., 2008). similarities (genome structure and protein homology),
Acquired immune deficiency syndrome (AIDS) results HIV-1 groups M and N likely originated from chim-
when the density of CD4 T cells drops below 200 cells panzees (Pan troglodytes troglodytes) in Cameroon
per microliter of blood or when one of several indicator (Figure 27.4), and group O from Western lowland gor-
conditions are present (e.g., Kaposi’s sarcoma, Bur- illas (Gorilla gorilla) in Cameroon. HIV-2 originated
kitt’s lymphoma, infection with Toxoplasma, Pneumo- from sooty mangabeys (Cercocebus atys) in Côte
cystis, Cryptosporidium, Cytomegalovirus, etc.). Death d’Ivoire (Gao et al., 1999; Hahn et al., 2000; Peeters
results from opportunistic infection, cancers, wasting, et al., 2002; Bailes et al., 2003; Apetrei et al., 2005;
and neurological complications. Santiago et al., 2005; Keele et al., 2006; Van Heuverswyn
The estimated global prevalence of HIV is approxi- et al., 2006).
mately 33 million people with the highest prevalence There are currently 18 described strains of SIV
rates are found in sub-Saharan Africa (Joint United found in 38 species of nonhuman primates, including
National Programme on HIV/AIDS, 2008). Approxi- vervets, mangabeys, guenons, colobus, talapoins, man-
mately 2.7 million people are infected each year, with drills, patas, baboons, chimpanzees, and gorillas (Gao
approximately 2 million deaths annually. Within the et al., 1999; Hahn et al., 2000; Peeters et al., 2002;
United States, the majority of those infected are young Bailes et al., 2003; Apetrei et al., 2005; Santiago et al.,
males (Hall et al., 2008). Although the majority of those 2005; Keele et al., 2006; Van Heuverswyn et al., 2006).
infected in the United States are white non-Hispanics, Simian immunodeficiency viruses likely entered into
death rates are highest in the non-Hispanic black the human population in West Africa due to cutaneous
populations. However, life expectancy of HIV-infected or mucous membrane exposure to infected nonhuman
individuals within the United States has generally primates. Direct exposure to nonhuman primate blood
increased due to the use of highly active anti-retroviral through hunting and butchering is common (Wolfe
therapy (HAART), which includes reverse transcriptase et al., 2004), and SIV has been identified in nonhuman
blockers like azidothymidine (AZT), integrase blockers, primate bushmeat and pet animals in West Africa
and protease inhibitors. Still the most effective means (Peeters et al., 2002; Apetrei et al., 2005). Simian
at prevention is to eliminate high-risk behaviors. immunodeficiency viruses have also been reported in
Because of the long latency period of infection, a sig- bushmeat hunters in Cameroon (Kalish et al., 2005).
nificant proportion of infected individuals are unaware Through the hunting and butchering of nonhuman
of their infection. Approximately one-quarter of all primates in West Africa, SIV likely entered into the
those infected with HIV in the United States are human population many times and became estab-
unaware of their HIV infection (Hall et al., 2008). lished within the human population as HIV around
The modern HIV epidemic was first recognized as a 1900 in what is now the Democratic Republic of Congo
cluster of Pneumocystis carinii pneumonia cases in (Worobey et al., 2008). Despite infecting humans for
homosexual men in Los Angeles, California in 1981. only just over 100 years, several allelic variants appear
to provide protective responses against HIV infection. birds, and mammals (Garnham, 1966; Coatney et al.,
Historic selection pressure through high mortality 1971; Levine, 1988). Of these, only 4 naturally infect
rates may account for the presence of these restriction humans (P. falciparum, vivax, ovale, and malariae),
genes within human populations, but the influence of 19 infect nonhuman primates, and 19 infect various
genetic drift and gene flow should not be discounted. other mammals. The majority of Plasmodium species
Alterations in the morphology of the chemokine core- infect birds and reptiles. The parasites are transmitted
ceptors that the virus uses to bind to and enter host by over fifty species of female Anopheles mosquitoes
cells can confer resistance against HIV infection. Sev- (Kiszewski et al., 2004). During the Plasmodium life
eral of these AIDS restriction genes that delay the onset cycle (Figure 27.5), sporozoites are injected from the
of AIDS include CCR2-64I, HLA-B*27 and B*57 and mosquito’s salivary glands into the vertebrate host. The
others (Dean et al., 2002; Winkler et al., 2004). Individ- sporozoites penetrate the parenchymal cells of the liver
uals homozygous for CCR5-d32 can have complete where they remain for a variable period of time and
resistance against infection (Zimmerman et al., 1997). asexually reproduce (“exo-erythrocytic schizogony”).
The CCR5-d32 allele is found at high frequencies in Schizonts develop, which rupture to release merozoites
many European populations (e.g., 15% in Scandinavia, into the vertebrate blood stream. These merozoites
5% in Italy) (Stephens et al., 1998). Galvani and Slatkin invade red blood cells (erythrocytes), in which they
(2003) hypothesized that the huge amount of deaths develop into trophozoites, the form of the parasite that
due to plague (Yersinia pestis) and smallpox (Variola essentially feeds off of the nutrient supply of the eryth-
major) caused selection pressure to increase the fre- rocyte. The trophozoites undergo erythrocytic schizog-
quency of the mutation. However, while there is evi- ony to produce either more merozoites (which reinfect
dence that CCR5-deficient macrophages have reduced surrounding red blood cells) or the sexual gametocytes
uptake of Y. pestis in vitro, the mutation appears to (macro and micro). The gameocytes are ingested by the
have no protective effect in mice artificially infected Anopheles mosquito, after which they escape the eryth-
with Y. pestis (Mecsas et al., 2004). Furthermore, rocyte (‘exflagellation’). Within the gut of the mosquito,
recent data suggest that the CCR5 mutation is approxi- the male and female gametes fuse and form a fertilized
mately 5000 years old, which predates the outbreaks of ookinete. The ookinete develops into an oocyst which is
plague and smallpox in Europe (Duncan et al., 2005; implanted into the stomach wall of the mosquito.
Hummel et al., 2005; Sabeti et al., 2005). With current There it undergoes sporogony. The oocyst eventually
selection pressures, this HIV-resistance genotype may ruptures to release many sporozoites which migrate to
increase to over 50% in South Africans within 100 the mosquito’s salivary glands. The sporozoites are
years (Galvani and Slatkin, 2003). Such a change released into the vertebrate host during the next
would not come without an evolutionary cost though: blood-meal (see http://www.dpd.cdc.gov/DPDx/HTML/
individuals homozygous for the CCR5-d32 allele are at malaria.htm).
increased risk of fatal outcome from West Nile virus In humans, malaria causes ‘flu-like nausea with
due to altered leukocyte trafficking to the brain (Glass headache and muscle pain. The parxoysms of fever
et al., 2006). As discussed earlier, health-related adap- and shivering followed by sweating and fatigue corres-
tations are constrained by trade-offs. pond with the length of shizogony and the synchron-
ous rupture of schizonts: either every 48 hours (tertian:
Malaria vivax, ovale, falciparum) or 72 hours (quartan: malar-
Malaria is presently endemic in most tropical regions iae). Malaria can cause liver, spleen, and kidney failure,
of the world, with approximately one billion people and cardiovascular and placental damage. Plasmodium
at risk of acquiring malaria (Guerra et al., 2008). falciparum-infected red blood cells are capable of
The global incidence is estimated to be more than adhering to one another, to noninfected cells, and to
300 million new clinical cases each year (Trigg and cerebral microvasculature, causing seizure and coma
Kondrachine, 1998) with millions of deaths from mal- (Taylor et al., 2004). Immune responses include cell-
aria annually, a majority occurring in children (World and antibody-mediated ones, with primary activation
Health Organization, 1999). Five to ten percent of chil- of proinflammatory cytokines, including interleukin
dren born in tropical Africa will likely die from malaria 12, TNF-a, and IFN-g (Stevenson and Riley, 2004).
before the age of five (World Health Organization, Acquisition of effective immune responses to malaria
1999; Carter and Mendis, 2002). The economic and requires repeated exposure and inoculation (Carter
social impacts of this disease are enormous (Gallup and Mendis, 2002).
and Sachs, 2001). The evolutionary history of human malaria is an
Malaria is a mosquito-borne disease caused by interesting one. These parasites are likely descended
protozoa of the genus Plasmodium (phylum Apicom- from a coccidian ancestor that first parasitized the
plexa, suborder Haemosporidiidea, family Plasmodii- intestinal tract of either a reptile host (Garnham,
dae), with 172 named species that parasitize reptiles, 1966; Coatney et al., 1971) or aquatic invertebrate
i = Infective stage
d = Diagnostic stage Human liver stages
Liver cell Infected

liver cell
Mosquito stages 2
Ruptured 1 i
12
oocyst Mosquito takes A
a blood meal Exo-erythrocytic cycle
Release of (injects sporozoites)
11 Oocyst sporozoites
i Ruptured schizont
4 3
Schizont
C
Sporogonic Cycle Human blood stages
5 Immature
trophozoite
10 Ookinete 8 (ring stage)
Mosquito takes d
a blood meal
(ingests gametocytes)
Macrogametocyte
B
Erythrocytic cycle Mature d
trophozoite
Microgamete entering
macrogamete 9
P.falciparum 6
Exflagellated Ruptured
microgametocyte schizont
7 Schizont d
Gametocytes d 7
P.vivax Gametocytes
P.ovale
P.malariae
27.5. Lifecycle of Plasmodium. The malaria parasite life cycle involves two hosts. During a blood meal,
a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host (1).
Sporozoites infect liver cells (2) and mature into schizonts (3), which rupture and release merozoites (4).
(Of note, in P. vivax and P. ovale a dormant stage [hypnozoites] can persist in the liver and cause
relapses by invading the bloodstream weeks, or even years later.) After this initial replication in the
liver (exo-erythrocytic schizogony [A]), the parasites undergo asexual multiplication in the erythrocytes
(erythrocytic schizogony [B]). Merozoites infect red blood cells (5). The ring stage trophozoites mature
into schizonts, which rupture releasing merozoites (6). Some parasites differentiate into sexual eryth-
rocytic stages (gametocytes) (7). Blood stage parasites are responsible for the clinical manifestations
of the disease. The gametocytes, male (microgametocytes) and female (macrogametocytes), are
ingested by an Anopheles mosquito during a blood meal (8). The parasites’ multiplication in the
mosquito is known as the sporogonic cycle [C]. While in the mosquito’s stomach, the microgametes
penetrate the macrogametes generating zygotes (9). The zygotes in turn become motile and elong-
ated (ookinetes) (10), which invade the midgut wall of the mosquito where they develop into
oocysts (11). The oocysts grow, rupture, and release sporozoites (12), which make their way to the
mosquito’s salivary glands. Inoculation of the sporozoites (1) into a new human host perpetuates
the malaria life cycle. Figure and caption reprinted with permission from the US Centers for Disease
Control and Prevention: http://www.cdc.gov/malaria/biology/life_cycle.htm.
(Wilson and Williamson, 1997). Members of the genus Within the subgenus P. (Plasmodium), three malar-
Plasmodium likely diverged from the other Haemos- ial parasites naturally infect humans: vivax, ovale, and
poridiidea around 500 mya, perhaps around the time malariae. Plasmodium (Plasmodium) vivax (Grassi and
of the Cambrian explosion (Escalante and Ayala, Feletti, 1890) is a malarial parasite with worldwide
1994). Biting dipteran insects were later introduced distribution (Mendis et al., 2001). It possesses a tertian
into the parasite’s life cycle, possibly as early as 200 periodicity in which the process of schizogony lasts
million years ago (Carter and Mendis, 2002). The Plas- approximately 48 hours. Because hypnozoites can
modium radiation is thought to have occurred around remain dormant in the liver for years, relapse of illness
150 million years ago, which parallels the diversifica- can occur. A number of biomolecular investigations
tion of their vector’s lineages (Escalante and Ayala, suggest that P. (Plasmodium) vivax is closely related to
1995; Ayala et al., 1998). P. (Plasmodium) cynomolgi of macaques (McCutchan
et al., 1984; White, 1993; Waters et al., 1993). There are The subgenus P. (Laverania) contains only two
also a number of life history similarities between known species: P. (Laverania) falciparum (Welch,
P. vivax and the other tertian primate malarias, includ- 1897) is the virulent tertian parasite which naturally
ing P. schwetzi, P. cynomolgi, P. youngi, P. hylobati, infects humans; P. (Laverania) reichenowi (Sluiter
P. pitheci, P. eyelesi, and P. jefferyi (Coatney et al., et al., 1922) is the chimpanzee and gorilla counterpart.
1971). Genetic evidence from the cicumsporozoite pro- The two species are diagnosed by the presence of ring-
tein suggests that P. vivax evolved into P. simium in like trophozoites and crescentric gametocytes. Analysis
South and Central American monkeys (Lim et al., 2005). of mitochondrial DNA sequence polymorphism indi-
Whereas Escalante et al. (2005) have argued that cates that P. falciparum is most closely related to
P. vivax originated approximately 46 000–82 000 years P. reichenowi (Conway et al., 2000). Escalante et al.
before present in Asia from a macaque malaria, others (1995) analyzed the conserved regions of the gene
suggest that the parasite is much older and diverged coding for the circumsporozoite protein in various
from other primate malarias between 5 and 7 million Plasmodium species and confirmed the evolutionary
years ago (Jongwutiwes et al., 2005). Plasmodium vivax closeness of P. falciparum and P. reichenowi. In fact,
may have infected early Homo erectus in Asia and the two P. (Laverania) species are more closely related
spread to Africa sometime around 1 million years to one another than either are to other malarial para-
before present (Jongwutiwes et al., 2005). The parasite sites (Qari et al., 1996), and both are more closely
and its hominin hosts may have both experienced related to rodent and avian malarial parasites than to
significant population bottlenecks around 200 000– other primate malarial parasites (McCutchan et al.,
300 000 years ago (Jongwutiwes et al., 2005). Still other 1984). Escalante and Ayala (1994) present rRNA
more recent analyses suggest a most recent common evidence indicating that P. falciparum diverged from
ancestor of all P. vivax at 600 000 (Tanabe et al., 2007) P. reichenowi at approximately the same time that
or even 10 000 (Leclerc et al., 2004) years before chimpanzees and other hominins did, 5–10 million
present. years ago. In contrast, analysis of Dhfr and Ts genes
Plasmodium (Plasmodium) ovale (Stephens, 1922) is suggest that all extant populations of P. falciparum
a human tertian malarial parasite that is most common may be recently derived from a single ancestral stock,
in West Africa, New Guinea, and the Phillipines. Like the most recent common ancestor of which may have
Plasmodium vivax, hypnozoites of Plasmodium ovale lived between 25 000 and 58 000 years ago (Rich et al.,
can remain dormant in the liver for years, relapse of 1998). Extremely low nucleotide polymorphism is con-
illness can occur. This species is morphologically very sistent with a recent origin for P. falciparum (Rich
similar to P. vivax, although P. (Plasmodium) ovale pos- et al., 1998; Conway et al., 2000; Volkman et al., 2001;
sesses very characteristic oocyst and exoerythrocytic Carter and Mendis, 2002; Hartl, 2004). Worldwide cli-
morphology with very large nuclei (Garnham, 1966). matic changes throughout the last glaciation and the
Plasmodium (Plasmodium) ovale also bears some mor- advent of agriculture would have facilitated the spread
phological resemblance to P. simium of howler of the Anopheles gambiae vector responsible for the
monkeys (Garnham, 1966; Coatney et al., 1971). There radiation of Plasmodium (Coluzzi, 1999). During this
appear to be no close extant genetic relatives of P. ovale agrarian revolution, higher density, sedentary human
(Ayala et al., 1998). populations provided mosquitoes with necessary
Plasmodium (Plasmodium) malariae (Grassi and bloodmeals and potential mosquito breeding sites
Feletti, 1890) is the malarial parasite responsible for (Livingstone, 1958; Hartl, 2004).
causing quartan fever (72 hour schizogony) in Still other analyses using mitochondrial DNA sug-
humans. This parasite can remain in peripheral cir- gest an origin of more than 100 000 years before pre-
culation of human hosts for years. Some investigators sent for P. falciparum (Hughes and Verra, 2001). Joy
have suggested that there is a phylogenetic connec- et al. (2003) have predicted, based on mitochondrial
tion between P. malariae of humans, P. hylobati of DNA evidence, that P. falciparum really began to
gibbons, and P. brasilianum of New World monkeys spread within the human populations in Africa around
since all of the parasites exhibit quartan periodicity, 10 000 years ago. There is obviously great discrepancy
coarse pigment and dense cytoplasm (White, 1993). in these dates, and it will be important to continue to
Escalante et al. (1995) analyzed the conserved regions elucidate the phylogenetic history of these parasites.
of the gene coding for the circumsporozoite protein As malaria has been such a large evolutionary
(a surface protein expressed at the sporozoite stage) driving force for humans, we have developed several
in various Plasmodium species and found that resistance genetic polymorphisms (for review, see
P. malariae was indistinguishable from P. brasilia- Carter and Mendis, 2002). Some of the major hemoglo-
num. The genetic similarity between the two species binopathies, enzymopathies, and erythrocyte variants
indicates that host switching or host sharing may common today include sickle cell disorder, the O blood
have recently occurred. group, hemoglobins C and E, various glycophorins
and human leukocyte antigens, ovalocytosis, a- and (Tournamille et al., 1995). Both G6PD deficiency and
b-thalassemias, glucose-6-phosphate-dehydrogenase the Duffy-negative allele are thought to have evolved
(G6PD) deficiency, and Duffy antigen receptor negativ- approximately 10 000 years before present, corres-
ity (Livingstone, 1971; Weatherall and Clegg, 2001; ponding with the spread of agriculture (Carter and
Carter and Mendis, 2002; Kwiatkowski, 2005). Mendis, 2002; Tishkoff et al., 2001). Interestingly, a
Sickle cell disorder is an autosomal recessive con- Duffy-negative genotype ( 46C/C) is now associated
dition caused by a single-point mutation from glutam- with increased susceptibility to HIV-1 infection, but
ate to valine in the sixth position of the b-chain of slower disease progression, in African-American indi-
hemoglobin. The condition is found throughout Africa, viduals (He et al., 2008).
India, the Middle East, and the Mediterranean (Allison,
1954; Livingstone, 1967). In the homozygous state, Emerging infectious diseases
sickle cell anemia causes significant morbidity and “Emerging infectious diseases” are those that have
mortality (Weatherall and Clegg, 2001). Although the recently increased in incidence, expanded in geo-
exact protective mechanism against malaria is equivo- graphic range, moved into a new host population, or
cal, in the heterozygous state this trait could confer are caused by newly evolved pathogens (Morens et al.,
resistance through increased clearance or reduced 2004; Weiss and McMichael, 2004). Today, examples
resetting of infected cells, reduced parasite growth in include dengue hemorrhagic fever, West Nile virus,
sickled cells, and enhanced immune responses against Nipah virus, and H5N1 avian influenza (Figure 27.6).
infected cells (Williams et al., 2005; Williams, 2006). However, just because new, potentially deadly diseases
The a- and b-thalassemias, caused by deletions or are emerging and evolving does not necessarily mean
mutations on chromosomes 16 and 11 with resultant that the entire modern human species will be wiped
alterations of the a- and b-chains of hemoglobin, are also out by some exotic airborne Ebola-like virus, as the
likely characterized by greater immune responses tow- cinema likes to portray. As illustrated above, humans
ards malaria-infected erythrocytes (Allen et al., 1997). have been very good at developing genotypic and
Hemoglobin C is found in West Africa and results phenotypic adaptations to combat infections. Interest-
from a single-point mutation from glutamate to lysine ingly, the primary causes of emerging infectious dis-
in the sixth position of the b-chain of hemoglobin. In eases in human populations have been through
the homozygous state, there is a significant protective anthropogenic modification of the physical and social
affect against death from P. falciparum (Modiano et al., environments (Daily and Ehrlich, 1996; Patz et al.,
2001). In contrast, the homozygous state of ovalocyto- 2004). In the short-term, remediation of the effects of
sis appears to always cause prenatal mortality (Genton these pathogens will be primarily accomplished by
et al., 1995). Ovalocytosis is caused by a 27-base-pair human behavioral changes rather than genotypic
deletion in the erythrocyte band 3 (AE1) gene (Allen adaptations.
et al., 1999). In the heterozygous state, erythrocytes Human and livestock populations continue to grow
become oval-shaped which may inhibit merozoite rapidly, increasing the number of hosts potentially
invasion as well as decrease cytoadherence of infected susceptible to novel infections. Mass transportation of
erythrocytes to cerebral microvessels. Individuals people, products, livestock, and vectors of disease
with blood group O also exhibit significantly less bind- bring each of these closer to one another, and more
ing between infected and uninfected erythrocytes quickly at that (Kimball et al., 2005). Population move-
(Rowe et al., 2007). Blood group O may have evolved ments due to war, social disruption, and rural-to-urban
as a mutation of blood group A in response to selective migration in addition to general urbanization increase
pressure from P. falciparum just prior to the major the densities of nonimmune human hosts and pose
migration of anatomically modern Homo sapiens significant sanitation problems. Natural disasters and
out of African around 100 000 years ago (Cserti and bioterrorism may destroy public-health infrastructure
Dzik, 2007). and other resources (Watson et al., 2007). Sex tourism,
More recent protective genotypic polymorphisms intravenous drug abuse, the reuse of injectable medical
include G6PD deficiency and the Duffy-negative allele. equipment, (“iatrogenic”) and improper disinfection or
The former is caused by several hundred mutational ineffective protective measures in hospitals (“nosoco-
variations of the X-linked G6PD gene (Ruwende et al., mial”) all contribute to the rapid evolution of resistant
1995). Again, the exact protective mechanism is and deadly pathogens.
unknown, but infected cells may be more susceptible Human encroachment into previously undisturbed
to phagocytosis or hemolysis. The Duffy-negative allele areas increases remote area accessibility and intro-
results in a mutation at the FY locus of the Duffy duces more vectors and reservoirs of infection to new
antigen receptor for chemikines (DARC). This muta- hosts. Encroachment, extensification of agricultural
tion eliminates a binding site on the surface of erythro- land, urban sprawl, and habitat fragmentation all alter
cytes which P. vivax requires for entry into host cells population densities and distributions of wildlife,
Multidrug-resistant tuberculosis
Cryptosporidiosis
Vancomycin-resistant Drug-resistant malaria
S. aureus
Cyclosporiasis SARS
Diphtheria
E. coli O157:H7 E. coli
Hepatitis C O157:H7
vCJD H5N1
Human Typhoid
Lyme disease influenza
monkeypox fever
West Nile virus
Vancomycin-
Anthrax resistant
bioterrorism S. aureus
Rift Valley
fever
HIV Nipah virus
Lassa fever
Whitewater
arroyo virus
Hendra virus
Hantavirus
pulmonary
syndrome Entervirus 71
Human monkeypox
Dengue
Yellow fever Plague
Cholera Marburg Ebola
hemorrhagic fever hemorrhagic fever
27.6. Examples of emerging infectious diseases. Figure reprinted with permission from Morens et al.
(2004).
which changes disease dynamics (Patz et al., 2004). horseshoe bat (genus Rhinolophus) (Li et al., 2005).
Deforestation results in loss of plant species and sub- These animals likely came into contact with civet
sequent loss of undiscovered therapeutic drugs. farms, possibly through the feeding of bats to farmed
Changes in water usage, such as during the construc- civets. Unfortunately, it took close to a year to contain
tion of dams, culverts, and irrigation systems, can the outbreak, in no small part because of the lag of case
increase the potential breeding sites of vector species reporting and under-reports of the actual casualties in
like mosquitoes and snails (Keiser et al., 2005; China (Parry, 2003). Fear of decreased tourism, travel,
Steinmann et al., 2006). Biodiversity loss due to global and trade eventually cost the region billions of dollars
climate change, deforestation, the spread of invasive and hundreds of lives. This is an excellent example of
species, overexploitation, and other causes reduces the how emphasis on national sovereignty over global soli-
buffer of hosts in an environment, increasing the like- darity can produce significant negative health effects
lihood of cross-species transmission (Maillard and for the global population (Heymann 2004, 2006).
Gonzalez, 2006). Humans have also caused altered vector and reser-
As discussed previously, the use of bushmeat has voir distributions through the production of
been the source of HIV. In fact, the majority of all greenhouse gases and global climate change. The Aedes
emerging pathogens in humans are zoonotic in origin aegypti mosquito has expanded its geographic range in
(Jones et al., 2008), and population, ecological, and response to increased global temperatures, resulting in
behavioral changes that increase contact with wildlife increased risk of Dengue virus in subtropical and tem-
exacerbate emergence of these pathogens (Daszak perate climates (Hales et al., 2002). Likewise, the risk
et al., 2000). Another example is the severe acute of Lyme disease (Borrelia burgdorferi) has increased
respiratory syndrome caused by a coronavirus (SARS- with elevated global temperatures (Brownstein et al.,
CoV). It is transmitted through aerosolized particles, 2005). The outbreak of Hantavirus pulmonary syn-
and symptoms include fever and pneumonia. Between drome in the southwestern United States in the early
November 2002 and April 2004, SARS resulted in 774 1990s was caused by heavy summer rains associated
confirmed deaths from 8098 cases in 29 countries with the El Niño Southern Oscillation effect and the
(Hughes, 2004; Morens et al., 2004). The outbreak ori- subsequent proliferation of pine nuts and deer mice
ginated in farmers and animal workers in the Foshan (Peromyscus maniculatus), the natural reservoir of the
Municipality of the Guangdong Province of China (Yu Hantaan virus (family Bunyaviridae) (Engelthaler
et al., 2003). Later, the virus was identified in Hima- et al., 1999)
layan palm civets (Paguna larvata), raccoon dogs (Nyc- Nipah virus is another excellent example of how
tereutes procuyoinboides), and Chinese ferret badgers human-induced ecological changes have altered the
(Melongdale moschata) sold in wet markets for con- risk of emerging infectious diseases. Nipah is a single-
sumption. The actual reservoir of the virus is the stranded RNA virus of the family Paramyxoviridae that
causes severe acute febrile encephalitis in humans. Its huge amount of commercial poultry produced today,
natural reservoir is the flying fox (genus Pteropus), and the likelihood of viral entry into the poultry and human
the virus has been identified in Malaysia, Singapore, populations from wild birds has increased. Although
and Bangladesh (Epstein et al., 2006). Between human-to-human transmission of the virus has been
October 1997 and February 2000, Nipah virus resulted suggested in several cases (Ungchusak et al., 2005), the
in 105 confirmed human fatalities in Malaysia. The avian influenza virus appears to bind to receptors deep
cause of the outbreak is now attributed to a complex in the human respiratory tract, which would limit
interaction of human-induced environmental changes. direct human transmission and decrease the likelihood
Specifically, fire-mediated deforestation for the expan- of a pandemic (Shinya et al., 2006). However, reliance
sion of oil palm plantations produced significant air on genetic adaptations against this epidemic is clearly
pollution in the region. Combined with a drought pro- unwise; human genotypic adaptations to such diseases
duced by the El Niño Southern Oscillation, the avail- will be delayed compared to rapid pathogen evolution.
ability of flowering and fruiting forest trees was reduced The mis-governance of epidemics with decentralized
(Chua et al., 2002). Bats (Pteropus vampyrus and Pter- testing, misdiagnoses, and underreporting of cases
opus hypomelanus) began feeding in human orchards has resulted in slow public health responses
that had been strategically planted next to pig farms so (Cyranoski, 2005; Normile, 2005). A future pandemic
as to use pig waste as fertilizer for the orchards. Bat could produce considerable economic burden due to
waste entered the pigsties and the virus amplified destruction of commercial poultry, high human
within the swine. Despite producing severe respiratory health-care costs and loss of productivity (Meltzer
disease (but low mortality), the infected pigs were dis- et al., 1999). An understanding of human evolution
tributed throughout Malaysia. Economic losses were against infectious disease is incomplete and inapplic-
enormous, ultimately because we were less mindful able for today’s epidemics without consideration of the
about the impacts of environmental change on animal social, political, and environmental causes of morbid-
ecology and human health than we should have been. ity and mortality, and the behaviors we might employ
Widespread, irreversible modification and overuse to ameliorate some of these challenges.
of our environments have been characteristics of most
human populations over the past few thousand years,
but particularly the past century. Such rapid modifica- DISCUSSION POINTS
tion of the physical and social environments has
increased our reliance on cultural adaptations against 1. What contributions can evolutionary biology make
disease over biological adaptations that take gener- to medicine?
ations to proliferate. The current avian influenza out- 2. How can environmental conditions during child
break illustrates the need for this realization. Influenza development affect immune functions?
is a single-stranded RNA virus of the family Orthomyx- 3. How does lymphocyte development resemble Dar-
oviridae, of three main types (A, B, and C), and classi- winian evolution by natural selection?
fied into subgroups according to its glycosylated 4. How do some infectious pathogens evolve high
surface antigens: hemagglutinin (H) and neuramini- levels of virulence whereas others do not?
dase (N). The current avian influenza epidemic that 5. What genotypic and phenotypic adaptations have
began in 2003 is caused by a type A, H5N1 virus. Influ- humans developed to combat malaria infection?
enza viruses are common in wild migratory waterfowl, 6. What are some of the social and environmental
particularly ducks, geese, swans, gulls, and terns (Chen causes of emerging infectious diseases?
et al., 2005; Olsen et al., 2006). Infection with the low
pathogenic forms is typically asymptomatic in the ACKNOWLEDGEMENTS
birds. However, the high pathogen forms can cause
significant mortality is some species, like bar-headed Paul Ewald, Lisa Becker, Sean Prall, Laurah Jones, and
geese. Influenza experts are concerned that such a two anonymous reviewers assisted with the production
virus could cause a devastating pandemic. The 1918 of this manuscript.
Spanish influenza (H1N1) pandemic that killed as
many as 50 million people was caused by an avian
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28 Complex Chronic Diseases
in Evolutionary Perspective
S. Boyd Eaton
From an evolutionary point of view, most complex Firstly, what is the evidence that we are still genetic
chronic diseases appear to be the result of imbalance, Stone Agers? Secondly, if our ancestral lifestyle was so
mismatch, between our genetic makeup and the condi- much healthier, why do we now live longer? And
tions of life in Westernized twenty-first century thirdly, chronic illnesses ordinarily become apparent
nations. The basic contentions (Eaton and Eaton, late in life. Isn’t it just because we live longer that we
1999a; Eaton et al., 2002a) are that: develop these disorders?
Ten thousand years is plenty of time for at least
1. The contemporary human genome was selected over
some genetic evolution to occur and, indeed, scientists
thousands of millennia during which our ancestral
have identified a number of genetic changes that have
line existed as prehuman primates who became
emerged since agriculture initiated the watershed
increasingly human-like until, during the period
alteration in human life conditions which has charac-
between 100 and 50 thousand years ago, they became
terized the last 10 millennia. The majority of these deal
behaviorly modern and lived as near equivalents of
with defenses against infectious diseases, the nature
hunter-gatherers studied during the last century.
of which has changed greatly since our ancestors lived
2. Our genetic makeup, especially that regarding our
as nomadic hunter-gatherers. Settled communities
core metabolic and physiologic characteristics, has
(with attendant sanitation problems), increased popu-
changed very little between the emergence of agri-
lation density, and intimate association with domesti-
culture, roughly 10 000 years ago, and the present.
cated animals promoted epidemic “crowd” diseases
3. On the other hand, cultural change during these past
which had previously been of far lesser importance.
10 millennia has progressed at an ever-accelerating
Genetic evolutionary responses included the sickle cell
rate. The resulting dissonance between what amount
condition and similar hemoglobinopathies (defenses
to Stone Age genes and Space Age lives fosters devel-
against malaria), and also alterations in the genetics
opment of multiple health disorders ranging from
of our immune system. The latter explain why, after
the potentially life threatening (cancer, pulmonary
initial contact with Westerners, Native Americans,
emphysema, heart attacks) to the more mundane,
Hawaiians, and other such groups experienced disas-
but still costly and uncomfortable conditions such
trous death rates from “childhood” infectious illnesses
as acne, high frequency hearing loss, myopia (near
which, in Old World cultures, had come to be infre-
sightedness), and dental caries.
quently fatal. Those populations who adopted dairying
These contentions make up the “discordance hypoth- and milk consumption developed persistence of intes-
esis” and its corollary is that the “afflictions of afflu- tinal lactase into adulthood. Almost all mammals
ence” might best be prevented by reincorporating the make the enzyme lactase during infancy because it
essentials of our ancestral living pattern into our con- allows digestion of lactose, the sugar in mothers’ milk.
temporary lives – ideally blending the best from the After weaning, ancestral humans, like other mammals,
past with best from the present. no longer needed lactase because they did not consume
dairy products. Animal husbandry made milk available
to adults; hence lactase persistence became selectively
OBJECTIONS TO THE EVOLUTIONARY beneficial.
APPROACH As our ancestors migrated from Africa to other
parts of the world, “races,” as we know them today,
On initially encountering these propositions, educated differentiated. However, it is important to remember
health-conscious individuals usually raise one or more that the identifying features that distinguish current
of three potential reservations (Eaton et al., 2002b): humans from varying geographical regions are largely
491
492 S. Boyd Eaton
superficial. To our eyes, Finns and Australian centuries, from around 40 in 1800 to almost 80 in
Aborigines look much more unlike than do mountain 2000. This unprecedented increase results from soci-
and lowland gorillas, but there is far greater genetic etal affluence (better housing, more affordable food,
dissimilarity between the gorillas. It appears that cheaper clothing), which has increased host resistance
cheetahs are the only mammalian species whose indi- to infectious agents, and from effective public health
vidual members are more genetically similar to each measures (immunizations, sanitary engineering,
other than are humans. safer food) which decrease microbial transmission.
A few other examples of “recent” genetic evolution Both factors work against contagious illnesses which
have been proposed: a decreased ability to smell, were the major causes of human mortality until the last
changes in genes affecting the liver’s capacity to detox- century. (In 1900, infectious diseases caused more
ify natural poisons, and, most controversially, genes deaths in the United States than did cancer and
affecting brain size and/or function. Some of the latter heart disease combined.) Increasingly sophisticated
are analogous to sickle cell condition: when a person medical care has also played a role, although less than
has only one such gene, the situation may be benefi- might be assumed.
cial, however, when two copies of the mutant gene are On the other hand, personal lifestyle choices
present, one from each parent, illness develops. affecting health – those targeted by health promotion
An example is Tay–Sachs disease, which is caused by advocates – have actually had a negative impact.
a single mutation and inherited in a fairly straightfor- Compared with the early 1900s, per capita cigarette
ward Mendelian pattern. Tay–Sachs and conditions smoking has increased 10-fold; daily physical activity,
like it are, apparently, unrelated to the common previously over 1000 kcal/day, has decreased to
chronic degenerative diseases like diabetes and athero- 500 kcal/day. For adult men, average body mass
sclerosis, which are influenced by many relevant genes, indices have increased from 23 to 28, 25 being con-
and whose inheritance is much more complicated. sidered the upper limit of normal. The failure rate
These genetic changes that have evolved during among candidates taking the Army’s induction physi-
the past 10 000 years are exceptions which prove a cal fitness test has become so high that the Pentagon
general rule: they are few in number and have little has seriously considered relaxing standards so that
effect on chronic illness susceptibility. Even though more candidates can achieve eligibility. Intake of diet-
some modifications have occurred, biologists, evolu- ary fiber has decreased while intake of sugars and
tionary theorists, paleontologists, and human geneti- sweeteners has doubled. The interval between menar-
cists concur that, genetically, we remain almost che and first full-term pregnancy has risen from
identical to our late Paleolithic ancestors. If agricul- 5 years to 15 and breast-feeding at 12 months
ture and industrialization had produced substantial (19.4%) is now one third what it was in 1912–1919
alteration, there should be categorical, “taxonomic” (58%). All these changes increase risk for one or more
genetic differences between peoples whose ancestors chronic illnesses.
have been farmers for thousands of years (e.g. Near The effect of increasing life expectancy on age-
Easterners, Mayans, Chinese, etc.) and groups whose related chronic diseases is another potential stumbling
ancestors have been foragers until the past gener- block. A population with average life expectancy of
ation or two (e.g. !Kung San Bushmen, Paraguayan 40 years will inevitably have much lower mortality
Aché, Australian Aborigines, etc.). Apart from genes from cancer, heart disease, diabetes, and stroke than
affecting resistance to infectious disease, no such will a population with an average life expectancy of 75.
markers have been identified. To this extent, comparisons between recently studied
The second question, regarding life expectancy hunter-gatherers (imperfect, but the best available sur-
now versus the Stone Age, disturbs nearly everyone rogates for prehistoric Stone Agers) and citizens of
on initial consideration of the discordance hypothesis. affluent Western nations are invalid. Of course dis-
The best available estimates are that until about 1800 eases whose frequency increases with age will cause
average human life expectancy was relatively constant more deaths in a society with a greater proportion of
at 30 to 40 years for as far back as can be determined. older individuals.
The figure was likely less in urban centers until the This coin has another side, however. While chronic
past century: estimates for London in the 1660s range degenerative diseases generally produce mortality in
between 18 and 27 years! Infectious illnesses were later life, they begin much earlier, often in childhood.
the major killers, especially those affecting children. This allows comparison between age-matched younger
Individuals who reached age 40 are thought to have members of industrial and technologically primitive
had an expectation of further life only moderately less societies. Biomarkers of developing abnormality such
than that of contemporary humans at the same age. as obesity, rising blood pressure, nonobstructive cor-
In affluent Westernized nations, average life onary atherosclerosis, and insulin resistance are
expectancy has nearly doubled over the past two common among the former, but rare in the latter.
Complex Chronic Diseases in Evolutionary Perspective 493
Measurements of muscular strength and aerobic to, chronic diseases. This expectation has been well-
power (endurance) reveal similar discrepancies, again substantiated: dozens to hundreds of genes have been
favoring individuals whose lives more closely resemble found to play a role for most illnesses in this category:
the ancestral pattern. About 20% of hunter-gatherers 250 and counting for obesity alone. There are excep-
reach age 60 or beyond, but even in this age-bracket, tions such as hemoglobinopathies (e.g. sickle cell
members of foraging and other technologically primi- anemia), retinoblastoma, and phenylketonuria, but
tive cultures appear almost completely free from mani- the rule holds for the most widespread, numerically
festations of most chronic degenerative diseases important chronic conditions.
(osteoarthritis is an exception). Together, these obser-
vations strongly suggest that it is current Western life-
style rather than age alone that promotes those CATEGORIES OF DISCORDANCE
“afflictions of affluence” the prevention of which is a
major goal of contemporary health promotion efforts. It is through their impact on risk factors that the
cultural changes which have accumulated since agri-
culture’s emergence influence chronic disease propa-
WHAT ARE COMPLEX CHRONIC gation. These cultural novelties fall into several
DEGENERATIVE DISEASES? categories, but in all cases the new conditions appear
to adversely affect human health.
Illnesses in this category account for the overwhelming
majority of deaths and disability in Westernized
Nutrition
nations. Such disorders are generally characterized
by an uncertain etiology, multiple risk factors, a long There is surprisingly little overlap between current
latency period, a protracted course of illness, a non- foods and those of the Paleolithic (Cordain et al.,
contagious origin, functional impairment or disability, 2002, 2005; Eaton, 2006). We get most of our calories
and, in many cases, incurability. Examples include from grains, domesticated livestock, dairy products,
asthma, arthritis, cancer, cardiovascular diseases and refined sugars, but preagricultural humans ate
(including stroke and heart attack), and diabetes. naturally occurring plant foods and wild game.
Of course, generalizations of this nature are subject They used almost no cereal grains, no dairy foods,
to many exceptions and qualifications. Fortunately, no separated oils, no commercial processing, and
many cancers are curable. There is increasing evidence they had no sources of “empty calories.” People in
that chronic, low-grade infections may actually be the Stone Age consumed about twice the animal
a prerequisite for several “noncontagious” chronic ill- protein current Westerners do. The proportion of
nesses, including both malignancies and atheroscler- total fat in Paleolithic diets was roughly equal to that
osis. The relationship appears to be that infection is a for contemporary Americans – about 35%; however,
necessary, but not sufficient, causal factor. Sudden intake of serum-cholesterol raising fat was nearly
death is the initial clinical manifestation for many always far less than at present, and there was
individuals with coronary heart disease. The under- more dietary long-chain (C20 and above) polyunsatur-
lying arterial plaque formation may have taken ated fatty acids. These are thought to be the most
decades to reach the critical level, but from the biologically significant of the fatty acids because
patient’s subjective viewpoint, the disorder is hardly they are necessary components of neurons and
protracted and there has been no premonitory func- required for eicosanoid synthesis. The preagricultural
tional impairment. essential fatty acid ratio (o-6:o-3) was perhaps 3:1; for
One almost invariable attribute of chronic degen- average Americans it approximates 10:1 or more – an
erative diseases is the necessary interaction of multiple imbalance likely to promote atherogenesis. Dietary
causative influences – risk factors. Tobacco abuse, cholesterol content exceeded current US levels because
heavy alcohol ingestion, and inadequate dietary both lean wild game and fatty supermarket steak meat
antioxidant intake are all implicated for esophageal contain cholesterol. Carbohydrate consumption was
cancer. These elements potentiate each other’s effects less than at present, but came almost exclusively
in a multiplicative rather than a simple additive from fruits and vegetables, not from cereals, refined
fashion. Similarly, abnormal body composition (hyper- sugars, and dairy products. The latter provide more
adiposity, sarcopenia), excessive intake of high glycemic- readily absorbable “insulinogenic” glucose – thus
load foods, and physical inactivity combine to induce increasing dietary glycemic load. That ancestral
insulin resistance and, increasingly often, type II humans ate thrice the fruits and vegetables most afflu-
diabetes. That multiple risk factors affect chronic dis- ent Westerners do should have enhanced their antioxi-
ease incidence implies the existence of numerous genes dant capacity relative to ours. Compared with the
which are involved in the development of, or resistance typical American pattern, Paleolithic diets generally
494 S. Boyd Eaton
provided less sodium, but more potassium, fiber to first birth) interval was only 3 years, versus about
(soluble and insoluble), micronutrients, and, probably, 12 years for average Americans and Europeans.
phytochemicals. Before agriculture the net metabolic Foragers who lived through their full reproductive
impact of human foods was slightly alkalotic, tending span had high parity: typically 6 live births vs. 1.8 for
to raise bodily pH. Contemporary foods, especially Americans. Nursing was obligatory, intensive
dairy products and those made from grains, have (on demand, not on schedule), and commonly lasted
the opposite – acidotic – effect and tend to slightly three years. Only about 50% of American babies are
lower bodily pH (Sebastian, 2005). Stabilizing nursed at all and mean nursing duration is barely
homeostatic biochemical mechanisms largely correct 3 months. Age at menopause is hard to ascertain for
for this influence, but over decades, the result is exces- forager women, but menses apparently cease some-
sive skeletal calcium loss and, consequently, what earlier than in affluent societies.
osteoporosis. New reproductive patterns and the associated
These differences are pertinent to several areas ovulatory differential (three times as many ovulations
of current nutrition-related research: e.g., o-3 fatty for Westerners not using oral contraceptives) are
acids and depression; o-6:o-3 ratios and coronary associated with increased risk for cancers of the
heart disease; fruits, vegetables, and phytochemicals breast, endometrium, and ovary. For example, imma-
as cancer preventive agents; optimal versus minimal ture breast lobules form at puberty; their rapidly
requirements of vitamins and minerals; dietary dividing cells are relatively susceptible to natural
sodium, hypertension, and overall mortality; and the mutation, genotoxic carcinogens, and clonal promo-
appropriate contribution of fats to dietary energy. tion. At first full-term pregnancy most lobules differ-
entiate into mature forms whose cells divide more
slowly and are hence more resistant. Prolonged nubil-
Physical exertion
ity thus extends a period of high susceptibility to
Through nearly all of human evolution, physical carcinogenesis.
exertion and food procurement have been inextricably
linked; in the past people had to work, physically,
Infection
in order to eat. Hierarchical social stratification
uncoupled this relationship for elites; industrializa- Relationships between humans and microbes were
tion and mechanization have completed the dissoci- altered by the rise of agriculture. Higher population
ation for practically everyone. Prior to the industrial density, frequent long-distance contacts, settled living,
era humans are estimated to have required a total and interactions with domesticated animals vastly
of about 3000 kcal (12 MJ) daily; for current affluent increased pathogen transmission. As a result, certain
populations comparable estimates are 2000 kcal infections assumed greater importance, becoming
(8 MJ) or less. This change has resulted from selective forces that have subsequently affected the
decreased energy expenditure through physical human genome (e.g., malaria, typhoid fever). More
exertion: about 20 kcal/kg/day (84 kJ) for hunter- recently, improved sanitation has reduced transmis-
gatherers versus <5 kcal/kg/day (21 kJ) for sedentary sion, a pivotal contribution to the past two centuries’
Westerners – a four-fold differential (Eaton and increase in average life-expectancy. Discovery of
Eaton, 2003). antibiotics had dramatic impact, but intensive usage,
Exercise has important effects on aerobic power, including incorporation into animal feeds, has led to
muscular strength, and skeletal robusticity, all of the emergence of resistant organisms. Consequently,
which were substantially greater for ancestral popula- “preventive” anti-infective chemotherapy must now
tions. Exercise likely affects the incidence of age- aim at minimizing resistance as well as attaining
related fractures, some cancers, and atherosclerosis. clinical efficacy. To this end, mathematical models
Obligatory exertion promoted greater lean body mass integrating classic pharmacological approaches
while attenuating adipose tissue, thereby reducing type with the principles of evolutionary biology may help
II diabetes risk for our ancestors. optimize treatment protocols. Attempts to reduce
pathogen virulence may also benefit from Darwinian
considerations. For example, vaccines directed against
Reproduction
virulence-enhancing microbial antigens might dispro-
Studies of women in foraging and other traditional portionately affect dangerous strains and promote
settings suggest substantial differences between pat- their displacement by milder variants (Eaton et al.,
terns of ancestral and modern reproduction (Eaton 2002a).
and Eaton, 1999b Ellison, 2001). For preindustrial While adequate food, public health measures, and
women menarche was later (16 vs. 12.5 years) and first medical interventions have lowered infectious disease
birth earlier (~19 years) so that the nubility (menarche mortality during the past century, the megapolitan
crowding and unparalleled mobility in current affluent Growth and development

nations have probably increased transmission of
In Western populations, less frequent and severe child-
certain organisms, especially those spread by sexual
hood infection, sharply reduced exercise requirements,
and respiratory contact. This phenomenon could
unprecedented caloric availability, and epigenetic
affect chronic disease prevalence: there are well-
influences on maternal–fetal relationships (which are
established relationships between viral infections
only now becoming understood) result in rapid bodily
and certain cancers as well as intriguing hints of
growth and early sexual maturation. Average adult
a causal link between microbes and atherosclerosis.
height is asymptotically approaching a maximum
Epidemiological correlation between infectious expos-
while age at menarche has fallen to about 12.5 years,
ure rates and incidence of chronic “noninfectious”
probably near the population’s genetic limit. Most
degenerative diseases might ultimately open new
recent hunter-gatherers have been short-statured,
avenues for preventive intervention via evolution-
reflecting the nutritional stress of foraging in marginal
based antibiotic prophylaxis and/or vaccine develop-
environments, but average height for Paleolithic
ment. Immunization against human papillomavirus,
humans (who lived in more fertile regions) appears to
which is strongly linked to development of cervical
have roughly equaled that at present. Nevertheless,
cancer, is an example of this approach.
maturation may have been slower, as it is for athletic
The impact of public health measures and per-
young women in Western nations. Traditional North
sonal cleanliness may not have been altogether posi-
African pastoralists – who have sufficient dietary pro-
tive: the hygiene hypothesis posits that allergic
tein, little access to empty calories, and high levels of
conditions and the so-called autoimmune diseases
physical exertion – may simulate the ancestral stand-
are undesirable side effects (Yazdanbaksh et al.,
ard. They experience later puberty and slower growth
2002). For our ancestors, genetically determined
in height than do Westerners, attaining full stature
host defences – white blood cells, antibodies, etc.
only in their early 20s; still, their average adult height
(see Chapter 27 of this volume) – resisted the near-
equals that of Europeans.
continuous onslaught of bacteria, parasites, hel-
Rapid growth is usually interpreted as a sign of
minths, and viruses. The human immune system has
societal health, but maximal is not necessarily optimal
been designed through evolutionary selection for
(Eaton et al., 2002a). The current experience of puberty
ongoing battle with our microscopic adversaries.
three years earlier than the hunter-gatherer average
But now the terms of engagement have changed so
may result in dissociation between psychological
that, in a very real sense, our immune system has
and sexual maturation, thus contributing to unwanted
become under-employed. Previously prevailing
teenage pregnancies as well as suboptimal parenting.
circumstances (repetitive, unrelenting exposure to
Both early menarche and youthful attainment of
infectious agents) fostered an immunoregulatory
adult stature are associated with increased breast
atmosphere which maintained focus on deleterious
cancer risk. Rapid bodily growth may also affect blood
microorganisms while protecting against injury to
pressure regulation if renal development is unable to
our own tissues. In contrast, contemporary conditions
keep pace allometrically, thus requiring compensatory
apparently fail to activate appropriate immunoregula-
blood pressure elevation to maintain homeostasis, and
tion so the immune system has become prone to
possibly establishing a pathophysiological trajectory
attacking our lungs (asthma), paranasal sinuses
towards subsequent hypertension. Also, in laboratory
(sinusitis, rhinitis), joints (various arthridides), bone
animals at least, slower growth during adolescence and
marrow (childhood leukemias), intestines (Crohn’s
early adulthood is associated with increased longevity –
disease, ulcerative colitis), brain (multiple sclerosis),
apparently independent of any effect on chronic disease
and pancreas (type I, “childhood” diabetes). These
susceptibility.
allergic or autoimmune disorders occur disproportio-
nately among affluent, urban, and perhaps otherwise
optimally hygienic populations for whom exposure to
Psychosocial factors
microorganisms is (presumably) especially reduced as
compared with prior human experience. Genes affecting human behavior are ancient and
For immunologists, rheumatologists, and others probably coevolved with our life history characteris-
concerned with diseases of this nature, the aim is tics. For example, prolongation of childhood during
to isolate those microbial constituents (antigens) hominid evolution may have facilitated learning
that previously acted to induce appropriate immuno- and correlated with brain expansion occurring
regulation and to create from meticulously selected over the same period. But, like current sedentism and
components vaccines that will guard against develop- diet, the social circumstances of contemporary exist-
ment of allergic/autoimmune diseases while maintain- ence are novel. Many factors believed to exert import-
ing adequate host defense against infection. ant influence on psychological development and
496 S. Boyd Eaton
interpersonal relations are profoundly different from TABLE 28.1. A partial list of discordance-related
what they are thought to have been during our evolu- diseases.
tionary past (Eaton et al., 2002a). Average birth
spacing is now closer, while nursing and physical Acne
contact between infants and adults is much reduced. Age-related fractures
In most affluent societies, babies do not sleep Alcoholism
with their mothers – a break from general primate Asthma
experience dating back many million years. Ancestral Cancer
childhood and adolescence were almost certainly char- “Childhood” infections
acterized by multiage play groups, less restrictive Cirrhosis
supervision, and intense small group interpersonal Coronary heart disease
dynamics quite different from the age-segregated, Dental caries
more structured routines of contemporary schools Dental malocclusion (impacted teeth)
and little leagues. Based on what we know about Depression
hunter-gatherers, Paleolithic teenagers had relatively Diabetes
clear societal expectations, not the exciting-but- Emphysema
daunting array of life choices which confronts young Epidemic infectious disease
people today. For adults, a global society has advan- Gingivitis (gum disease)
tages, but it differs radically from the more human- High frequency hearing loss
scale experience of our ancestors who lived, found Hypertension
their roles, and developed self-esteem in bands of
Lactose intolerance
15–50 people, most of whom were relatives. We have
Low back pain syndrome
little concrete evidence, but it seems likely that these
Myopia (near sightedness)
differences and others – frequent contact with
Obesity
strangers, conflicting social roles, wage labor, working
Osteoporosis
in bureaucracies, reduced support from kin, socio-
Peripheral vascular disease
economic societal stratification, and education that
Sickle cell anemia
questions social beliefs and ideologies – may contribute
to syndromes such as attention deficit/hyperactivity, Stroke
depression, anxiety disorders, and substance abuse.
of Europeans have BPs above 140/90 mmHg or are on

REPRESENTATIVE ILLNESSES anti-hypertensive medication. Also HT is becoming
increasingly common: in the United States, its preva-
Table 28.1 lists many chronic disorders, all of which lence rose 15% between 1990 and 2000.
can be considered discordance-related conditions. Across the globe, many cultures studied during the
Discussing each of these in detail would greatly exceed last century were found to have no HT (Table 28.2).
the length allowed for this chapter; consequently, four Their BPs averaged 110/70 mmHg – within the range
disparate ailments, whose ties to discordance vary newly designated as normal by the NIH. Members of
from the simple and straightforward to complicated normotensive cultures were not immune from HT
and indirect, will be analyzed as illustrative examples. because, when they adopted a Western lifestyle, either
by migration or by acculturation within their home-
land, their BP experience soon began to parallel that of
Hypertension
Americans and Europeans. These normal BP cultures
For decades blood pressure (BP) readings of 120/80 existed in varied climatic circumstances – in the arctic,
mmHg were considered normal, but recent studies the rainforest, the desert, and the savanna – but they
have shown that adverse health effects begin at pres- shared a number of essential similarities, each of
sures exceeding 115/75 mmHg. Accordingly, in 2003, which reprised, or continued, the experience of our
an National Institutes of Health (NIH) select commit- late Paleolithic ancestors and which were the recipro-
tee redefined “normal” as under 120/80 mmHg (Joint cal of postulated causal factors for HT.
National Committee, 2003). Blood pressures between High BP is a treacherous condition because, of
120/80 and139/89 mmHg are now considered prehy- itself, it produces no symptoms. It has become
pertensive, while BPs of 140/90 mmHg or above indi- known as the “silent killer” because its complications,
cate that hypertension (HT), or high BP is present. affecting the eyes, kidneys, brain, and heart, can be
Hypertension is rife in Westernized nations: 25% of deadly. Persons with HT double their risk of heart
North American adults and an even higher proportion attack and have four times more risk of stroke than
potassium (~2500 mg) each day. In contrast, for

TABLE 28.2. Normotensive populations.
Stone Agers, like all other terrestrial mammals,
Hunter-gatherers daily sodium intake (1000 mg/day) was far less
Kalahari San (Bushmen)
than that of potassium (7500 mg/day).
Alaskan Aleuts • Exercise 30 minutes or more on most days. Paleo-
Greenland Eskimos lithic humans, who had no motorized equipment or
Australian Aborigines draft animals, are estimated to have expended about
Congo Pygmies 1240 kcal as physical activity each day. (The 1240
Tanzanian Hadza kcal figure is the averaged value for adult males and
Agriculturalists females). The corresponding estimate for Ameri-
Mexican Tarahumara Indians cans is 555 kcal per day.
Panamanian Cuna Indians • Limit alcohol intake. Hunter-gatherers studied in
Kenyan Suba Tribesmen the last century were unable to make alcoholic bev-
Ugandan Tesot Tribesmen erages. Regular manufacture of such drinks almost
Guatamalan Maya Indians certainly postdates the agricultural revolution.
Gambian Tribesmen • Increase fruit and vegetable consumption.
In East Africa, the likely human homeland, fruit
Horticulturalists
Cook Island Polynesians and vegetables provided about 50% of our ances-
Highland New Guinea Tukisenta
tors’ food energy intake during the period around
50 000 years ago. In the United States, currently,
Venezuelan Yanamamo Indians
fruits and vegetables provide only about 16% of our
Pukapukan Polynesians
daily food energy and the contribution in Europe is
Solomon Islanders
even less.
Malaysian Aborigines
New Guinea Chimbu The take home message should be inescapable. The
Brazilian Caraja Indians life patterns of Stone Age humans protected against,
Chinese Noso (Lolo) Aborigines while our own lead to, development of high BP. Only a
Surinam Indians few of the normotensive populations in Table 28.2
New Guinea Bomai were hunter-gatherers, but, except for access to alco-
Brazilian Kren-Akorore Indians holic beverages, they all shared those characteristics
which typified ancestral life and which recent epi-
Pastoralists
demiological investigations have shown to reduce
Kenyan Samburu
risk for HT.
Kenyan Masai
Dental caries
do individuals with BPs of < 120/< 80. Untreated HT is
We cannot be sure about the frequency of HT for
a common cause of congestive heart failure; about half
the builders of Stonehenge nor for the Tong Dynasty
the cases of end-stage renal disease (kidney failure) are
Chinese, but teeth are the best preserved of all human
attributable to HT; and hypertensive retinopathy, very
remains at archaeological sites and, because of this,
common in persons with untreated HT, can lead to
the prevalence of dental caries (cavities) can be very
blindness.
reliably established at different time periods through-
In 2002, the NIH published a list of lifestyle modifi-
out human experience. While HT causation is almost
cations which, together, can greatly reduce a person’s
certainly a multifactorial process, the historical correl-
risk of developing HT (Whelton et al., 2002). Compar-
ation of dental caries with sugar consumption indi-
ing these recommendations with the corresponding
cates a less complicated genes risk factor causal
features of ancestral life illustrates how deviations
relationship.
from the life ways for which our genes were selected
Researchers have found that, for late Paleolithic
can lead to chronic disease:
humans before the emergence of agriculture, about
• Maintain normal weight. Body mass indices 1–2% of adult teeth showed caries (Brothwell, 1963).
(weight/height) between 18.5 and 25 are considered At that time there were no refined sugars. Studies of
normal. Studies of multiple hunter-gatherer groups recent hunter-gatherers revealed that they were very
reveal an average BMI of 21.5; for Americans, the fond of honey, but because it was available seasonally
2002 average was 28! and was both difficult and painful to obtain, the aver-
• Increase potassium and decrease sodium intake. age individual in such cultures consumed only about
Americans consume more sodium (~4000 mg) than 2 kg/year. It is likely that intake during the Stone Age
498 S. Boyd Eaton
was similar. During the Middle Ages bees had been curves for lung cancer, which in the early 1900s was
domesticated, so honey was more available and about considered one of the rarest forms of primary neo-
10% of teeth from medieval times have cavities. plasm, parallel those for cigarette consumption with
Cane sugar appears to have been developed around astonishing exactitude. There is a lag period of from
500 BCE in India, but it remained expensive – available 20 to 30 years (which indicates the time necessary
almost exclusively to the upper classes, until sugar for tobacco’s carcinogens to induce malignancy),
cane cultivation began in the West Indies and large- but both the rising and falling rates of pulmonary
scale production was initiated. Even in 1815, average carcinoma follow the cigarette usage rate with near
consumption in Britain, of honey and sugar, was only perfect alignment (Witschi, 2001).
about 7 kg/year. The second most important risk factor for lung
Industrialization made sugar cheap. By 1900 it had cancer is indoor exposure to radon, a radioactive gas,
become a staple and, at that period, 60–70% of teeth in which may account for about 10% of American lung
Britain were carious. In 2000, American sugar con- cancer deaths (Franklin and Samet, 2001). Radon
sumption was nearly 70 kg/year, but because of fluorid- exposure is another example of discordance: despite
ation, fluoride-containing toothpaste, and generally being called “cavemen,” Stone Agers spent far less of
improved dental care, the dental cavity rate has fallen their lives indoors than do affluent Westerners.
to 15–20% – only about 10 times what it was for our Recently studied hunger-gatherers, even those in
remote ancestors. colder, upper-latitude climates, spent very little time
in caves, rock shelters, or other places where radon
might have accumulated. Nearly all their lives, espe-
Lung cancer
cially during daytime, were spent outdoors. Living,
The relationship of lung cancer to cigarette smoking studying, and working indoors allows exposure to
is almost as straightforward as that of dental caries radon gas, which originates from the ground and from
to sugar. Tobacco is naturally indigenous to the building materials (stone, concrete, etc.) and accumu-
Americas, Australia, and a few Pacific Islands. lates in houses, stores, schools, office buildings, and
Australian Aborigines have chewed tobacco for many the like.
millennia, but for most humans, tobacco exposure
postdated the sixteenth-century voyages of explor-
Insulin resistance and diabetes
ation. Thereafter tobacco availability spread with
amazing rapidity, but it was mainly utilized as snuff, Most everyone knows that the prevalence of diabetes
for pipes and cigars, and as chewing tobacco. These is climbing rapidly, up nearly 5-fold, 500%, since 1960,
forms of tobacco usage fostered cancers of the throat, but the relationship between insulin resistance and
larynx, and mouth: Presidents Ulysses Grant and diabetes is less widely recognized. People who are
Grover Cleveland, and also Kaiser Frederick III of insulin resistant must secrete more than the usual
Germany, were victims illustrating this effect. amount of insulin (from the pancreas) to metabolize
Cigarettes apparently originated in Turkey and a given amount of ingested carbohydrate. Insulin
spread to Western Europe only after the Crimean War resistant individuals have a high risk of developing
(1854–1856) in which Turkey, Britain, and France were type II (adult onset) diabetes and they are also more
allied against Russia. Turkish officers introduced cig- likely to manifest HT, obesity, coronary heart disease,
arette smoking to their English and French counter- peripheral vascular disease, and the polycystic ovary
parts from whom it spread to upper-class Westerners. syndrome.
Still, cigarettes remained a minimal component of Like type II diabetes, insulin resistance frequency
overall tobacco usage (3% of all tobacco consumption is soaring and, also like diabetes, it is an affliction
in 1900) until World War I when cigarettes were issued, of affluence. Australian Aborigines, Japanese Ainu,
free, to soldiers as morale boosters. Thereafter cigar- Brazilian Amerindians, Efe pygmies from the Congo,
ette usage skyrocketed to a peak in the mid twentieth and !Kung San Bushmen from Africa’s Kalahari Desert
century. Subsequent to the US Surgeon General’s were all hunter-gatherers who exhibited exceptional
report in 1964, cigarette smoking in the United States insulin sensitivity – the converse of insulin resistance.
gradually declined. About 23% of US adults smoked These groups inhabited widely separated geographic
in 2006 versus about 46% in 1949, the peak year of regions, but they shared the characteristics of being
consumption. lean, exercising a great deal, and consuming few or
Cigars, pipes, chewing tobacco, and snuff expose no foods that have excessive insulin-raising (insulino-
the nose, oral cavity, throat, and larynx to tobacco’s tropic) effects.
effects, but generally spare the lower portions of the As obesity is so strongly linked to type II diabetes,
respiratory tract. Conversely, cigarette smoke is usu- weight, and especially weight for height, BMI, is com-
ally inhaled, so that it affects the lungs. The incidence monly thought of as particularly important. Actually
neither weight nor BMI is the critical factor. Rather, Carbohydrate consumption
body composition seems most closely related to both
diabetes and insulin resistance. Individuals with a Blood glucose elevation
greater proportion of fat are more likely, and those
Insulin release Insulin release
with a greater proportion of muscle, less likely to
develop insulin resistance. A descriptive expression is:
Fat Muscle
% body fat Muscle Fat
Insulin Resistance
% muscle mass
This relationship is easily explained (Eaton et al.,

Appropriate blood glucose Insufficient blood glucose
2002a). Fat cells and muscle cells have identical insulin reduction reduction: more insulin
receptors which “compete” for circulating insulin required
molecules. However, a given amount of fat, say 1 g, 28.1. Carbohydrate metabolism.
can extract much less glucose from the blood than can
a similar gram of muscle despite equivalent insulin
insulin receptors of visceral fat cells are much better
stimulation. In effect, insulin molecules interacting
positioned than are those of subcutaneous fat cells
with adipocyte receptors are being underutilized in
when it comes to competing with muscle cell insulin
comparison with the blood sugar lowering impact they
receptors for circulating insulin molecules. The apple-
could have achieved had they interacted with myocyte
shaped person has more visceral and the pear-shaped
insulin receptors.
person fewer visceral fat cells as a proportion of total
Physical activity is beneficial because it tends to
body fat content.
increase muscle tissue and decrease fat as proportions
Insulin resistance appears to be a biphasic process.
of body weight. Also, exercise increases muscle fitness,
Phase I (Figure 28.2a) is a classic example of
a correlate of muscle metabolic rate. A gram of fit
discordance at work. Body composition differing from
muscle extracts more glucose than a gram of unfit
the ancestral pattern (too much fat, too little muscle),
muscle, given equal exposure to insulin. When muscle
exacerbated by low-level muscle fitness produces insu-
fitness is taken into account, a more complete descrip-
lin receptor imbalance (too many fat cell receptors; too
tive expression is:
few and insufficiently active muscle cell receptors).
% body fat mass These factors interact with our recently adopted high
Insulin Resistance
% body muscle mass muscle fitness glycemic load diet to induce repetitive hyperinsuline-
mia. These phase I factors are responsible for the rising
Studies of recent hunter-gatherers showed them to be insulin resistance and type II diabetes prevalence
much fitter and far leaner than age-matched Western- during the past few decades.
ers. Also, the skeletal remains of Stone Age humans It is phase II (Figure 28.2b) that fascinates geneti-
reveal evidence of impressive muscularity, comparable cists and molecular biologists. Repetitive hyperinsuli-
to that of today’s superior athletes (such as Olym- nemia activates genetically determined intracellular
pians). These key factors affecting insulin resistance biochemical mechanisms (such as GLUT 4 trafficking)
nicely illustrate the discordance hypothesis: our gen- whose cumulative effect is to create intrinsic cellular
etic makeup is designed for ancestral circumstances resistance to the actions of insulin. Muscle, fat, and
and deviation from the Stone Age pattern promotes liver cells from phase I individuals react normally to
dysfunction. insulin (at least early in the condition); the problem at
Figure 28.1 diagrams carbohydrate metabolism this stage is tissue imbalance and muscle unfitness.
for Stone Age populations, whose end result was However, in phase II these tissues become less sensi-
appropriate blood glucose reduction, and for modern tive to insulin stimulation. The adaptive mechanisms
couch potatoes who require extra insulin secretion to induced by phase I’s repetitive hyperinsulinemia
achieve adequate blood glucose regulation. somehow make body tissues subnormally responsive.
Most health-conscious individuals have heard that The genetic and biomolecular phenomena involved in
a pear-shaped body configuration (big hips and upper this segue are complex and the subject of intense inves-
thighs) is preferable to an apple-shape (big midsec- tigative scrutiny, but cannot, in themselves, account for
tion). This difference relates largely to regional blood rising rates of insulin resistance and type II diabetes.
flow patterns. Intra-abdominal (visceral) blood flow is It remains to discuss insulinotropic foods
21% of total cardiac output at rest and much more (Lindeberg et al., 2007). These share the characteristics
following a meal. In contrast, cutaneous and subcuta- of being newly adopted dietary constituents, in the
neous blood flow is only 6% of total cardiac output evolutionary time frame, and of having special potency
at rest and less following a meal. It follows that the in raising serum insulin levels. The carbohydrate
500 S. Boyd Eaton
(a) (b)
Insulin resistance: Insulin resistance:
A biphasic process A biphasic process
Phase I Unfit muscle Phase II Intrinsic cellular

resistance
Abnormal Insulin (muscle, fat, liver)
body composition receptor Hyperinsulinemia
(hyperadiposity, imbalance
sarcopenia)
Phase I underlies the recent secular increase in diabetes Hyperinsulinemia Biomolecular

prevalence.
adaptive mechanisms
(genetically determined)
Phase II cannot explain recent secular increase in diabetes
prevalence.
28.2(a and b). The development of insulin resistance.
available from sugars and refined cereal grains comes and, as a discipline within the biological sciences,
in a form which is rapidly absorbed from the intestinal medicine should also be informed by evolutionary
tract, that is, these foods have a high “glycemic index.” awareness. The discordance hypothesis is an attempt
Also, both sugars and refined grains contain a high to connect the areas of disease causation and preven-
proportion of carbohydrate as a component of their tion with our growing knowledge of human evolution;
total weight so they are high “glycemic load” foods. in Kuhnian terms it represents a candidate paradigm
(Glycemic load ¼ glycemic index carbohydrate con- (Kuhn, 1996). As we learn more about the specifics of
tent per serving.) Rapid entry of glucose (from digested Paleolithic experience and as our understanding of
carbohydrate) – in large amounts – into the blood- human pathophysiology becomes better refined, some
stream causes excessive insulin release relative to the of the material presented in this chapter will undoubt-
ancestral condition, so both refined cereals and sugars edly require modification, but the basic points will
are insulinotropic. Dairy products are different: they almost certainly be confirmed:
have relatively low glycemic indices, yet produce dis-
• Our genetic makeup is ancient.
proportionately high insulin release. The mechanism
• “Rapid” cultural change has created discordance
involved is currently unknown, but they are also con-
between our genes and our lives.
sidered insulinotropic.
• This discordance, or mismatch, fosters develop-
From our genes’ standpoint all three food categor-
ment of most complex chronic degenerative
ies are Johnny-come-lately’s. Refined cereal grains
diseases.
were unavailable to Stone Agers who lacked the neces-
• Preventing these diseases, and health promotion
sary technology and who, in any case, consumed
in general, involves reversion towards the basic
cereals only during times of food shortage. Whole
essentials of ancestral existence (while, ideally, pre-
grains have been dietary staples since the advent of
serving the positive health effects of cultural
agriculture, but truly efficient milling appeared no
evolution).
earlier than the late nineteenth century. Now 85% of
the cereals consumed in the United States are refined.
We estimate that Paleolithic humans consumed
about 2 kg of sugar (as honey) a year. In 2000 average DISCUSSION POINTS
Americans consumed 70 kg/year. And Stone Agers had
no domesticated animals (except, perhaps, dogs in the 1. How similar are we genetically to preagricultural
latest phases). Consequently, adults during the entire humans?
extent of human and prehuman evolutionary experi- 2. Why is the rate of type II diabetes rising around the
ence had no dairy foods whatever. world?
3. Is there a “natural” diet for humans?
CONCLUSIONS 4. How do NIH recommendations for preventing high
blood pressure compare with our understanding of
Evolution is increasingly accepted as the core around the ancestral human lifestyle?
which our understanding of biology must be constructed, 5. What is the “Discordance Hypothesis”?
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Evolutionary health promotion. Preventive Medicine, 34,
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Cordain, L., Brand-Miller, J., Eaton, S. B.et al. (2002). Plant-
Ellison P. T. (2001). On Fertile Ground. A Natural History of
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Cordain, L., Eaton, S. B., Sebastian, A. et al. (2005). Origins
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Eaton, S. B. (2006). The ancestral human diet: what was it
American Medical Association, 289, 2560–2572.
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Eaton, S. B. and Eaton, S. B. III (1999a). The evolutionary
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Health and Disease, Stearns S. C. (ed.). Oxford: Oxford
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Eaton, S. B. and Eaton, S. B. III (1999b). Breast cancer in
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29 Evolutionary Medicine and the Causes
of Chronic Disease
Paul W. Ewald
The current integration of evolution with medicine is If pathogens have adaptations that allow them to evade
artificially narrow because it reflects the biases of the immune system, they can persist indefinitely. Ill-
medicine as a whole and the specializations of particu- nesses caused by such persistent pathogens tend to be
lar investigators. If evolutionary principles are to offer chronic. The three-month dividing line between acute
a fundamental framework for understanding medical and chronic diseases therefore corresponds roughly
issues they should help identify these biases and the with an immunological basis for rapid resolution of
areas over which integration needs to be broadened. infectious challenges versus protracted conflicts.
The chapter discusses this problem as it relates to The causes of chronic diseases are not well under-
evolutionary interpretations of chronic diseases. It also stood largely because the processes of causation tend
illustrates how an evolutionary perspective can provide to be inconspicuous and difficult to evaluate (Cochran
a broader framework for resolving the causes and con- et al., 2000). For the past century the prevailing view of
trol of chronic diseases, focusing on the greatest killers modern medicine has been that chronic diseases result
in prosperous societies – atherosclerosis and cancer. largely from interactions between a person&s genetic
vulnerabilities and environmental influences. These
interactions determine the rate at which the body
OVERVIEW OF CHRONIC DISEASES succumbs to chronic disease.
Evolutionary medicine has recast this problem
Chronic diseases account for about 70% of the mortal- by asking why the process of natural selection has
ity in the United States and other wealthy countries. resulted in the existing collection of vulnerabilities to
Most of this disease-induced mortality is attributable chronic disease (Nesse and Stearns, 2008). The investi-
to heart attacks, strokes, and cancer. In spite of this gative framework of evolutionary medicine integrates
importance, the causes of chronic diseases remain the mechanistic (proximate) explanations, which
largely unresolved. This situation represents a major address how biological processes work, with evolutio-
short-coming of modern medicine because under- nary (ultimate) explanations, which address why
standing the causes of disease enables prevention, biological evolution has resulted in these processes.
and prevention is the most effective way of eliminating Proximate causes of human diseases include human
the damage inflicted by disease. We can therefore alleles and environmental factors that contribute to
expect that a better understanding of the causes of pathogenesis. Ultimate causes explain why humans
chronic diseases will yield some of the most valuable have evolved to be vulnerable to such influences, and
contributions that any discipline can make to improve- if an environmental cause is a parasite why the parasite
ments in health. has evolved to cause this damage.
Chronic diseases can be defined broadly as diseases In evolutionary medicine investigations of the
that persist within individuals for a long time. The US causes of chronic disease generally focus on the differ-
National Center for Health Statistics considers “long” ences between ancestral and modern environments.
to mean persistence for at least three months. Although The prevailing emphasis is on the mismatch between
this dividing line between acute and chronic is some- our modern environment and our evolved biology.
what arbitrary, a biological basis for distinguishing Aspects of modern diets that differ from ancestral
acute and chronic diseases can be made for infectious diets, for example, are raised as explanations for
diseases. If an immune response can readily eliminate diseases such as atherosclerosis and diabetes (Eaton
an infection, it generally does so within several weeks. et al., 1988, Nesse and Williams, 1995; Gerber and
Infectious diseases that are controlled (or kill the host) Crews, 1999; Leonard, 2008). Modern changes in
during this period are generally considered acute. nondietary exposures to cigarette smoke, ultraviolet
502
Evolutionary Medicine and the Causes of Chronic Disease 503
radiation in light skinned people, or birth control, are acute diseases emphasize parasitic causes, whereas
suggested as reasons for increased rates of cancers studies of chronic diseases emphasize the evolved
(Williams and Nesse, 1991; Eaton et al., 1994; Nesse characteristics of humans and environmental factors
and Williams, 1994; Diamond, 2005). Increased life other than parasites. A central challenge for evolution-
span in modern environments is suggested as a reason ary medicine is to determine whether this discordance
for chronic diseases associated with old age (Nesse reflects a real difference between acute and chronic
and Williams, 1995; Austad 1997; Finch, 2007; Austad diseases, biases against considering infectious causes
and Finch, 2008). Human bodies are presumed to be of chronic diseases, or both.
vulnerable to such proximate causes of chronic dis- Although infectious causes of chronic diseases have
eases because exposure to these proximate causes been accepted for over a century, the clarity of hind-
has been too recent to purge these vulnerabilities sight shows that this category of causation has been
by natural selection. Evolutionary medicine also underappreciated in evolutionary medicine. Illnesses
considers the inability of natural selection to perfect such as peptic ulcers and cancers, for example, were
adaptations, due, for example, to constraints on deve- explained by the mismatches between modern and
lopmental processes or the limited power of natural ancient environments without consideration of infec-
selection to perfect adaptations (Nesse, 2008). tious causation, even when evidence implicating
These arguments of evolutionary medicine gener- infectious causation was well developed (e.g., Nesse
ally accept the consensus of nonevolutionary medicine and Williams, 1995). It is now broadly accepted that
on the proximate causes of disease and develop evolu- peptic ulcers, cancers of the stomach, liver, cervix, and
tionary explanations for these proximate causes. This oropharyngeal, and nasopharyngeal regions are caused
consensus of nonevolutionary medicine is generally largely by infectious processes (Ewald, 2000; Cochran
that the proximate causes of chronic diseases result et al., 2000; Greaves, 2000). The overlooking of infec-
from an interaction between human genetics and non- tious causation may be much more significant than
infectious environmental factors, the familiar gene by these examples indicate because, as will be discussed
environment explanations. But the proximate causes of in this chapter, evidence indicates that many other
chronic illness are still largely uncertain. If evolution- important chronic diseases, such as atherosclerosis,
ary medicine generates ultimate explanations for the Alzheimer&s disease, breast cancer, and schizophrenia,
wrong proximate explanations, the ultimate explan- may be caused largely by infectious processes.
ations will be wrong as well. It is therefore important To avoid a bias against identifying infectious
for research in evolutionary medicine to consider the causes, disease causation can be considered schemat-
full range of feasible proximate explanations of disease ically as a causal triangle with each apex of the triangle
to safeguard against offering incorrect ultimate expla- corresponding to one of the three categories of cau-
nations. Moreover, evolutionary insights may facilitate sation (Figure 29.1). The placement of any disease
evaluation of alternative proximate mechanisms of within the triangle emphasizes the relative importance
pathogenesis by distinguishing those mechanisms are of the three categories of disease causation. Diseases
evolutionarily feasible from those that are not. are placed closest to the vertex that corresponds to the
These arguments apply in principle to acute dis- primary cause of the disease, but the location within
eases, but the causes of acute diseases are understood the triangle (instead of at the vertex itself), emphasizes
better than are the causes of chronic diseases; there that other categories contribute to pathogenesis.
is therefore less danger of proposing an evolutionary A primary cause is defined as one that is necessary
explanation for an incorrect proximate mechanism of for the disease to occur. Prevention of the primary
acute diseases, and little need for new evolutionary cause(s) of a disease prevents the disease. Prevention
insights to identify the causal agents of acute diseases. of a secondary cause will reduce the frequency or
The overwhelming majority of acute diseases are severity of disease but will not prevent the disease
caused by parasitism, broadly defined to include multi- itself. Mycobacterium tuberculosis, for example, is a
cellular, cellular, and subcellular parasites (infectious primary cause of tuberculosis, because prevention of
diseases being defined as parasites that live in intimate Mycobacterium tuberculosis infection will prevent
association with host cells and tissues). The evolutio- tuberculosis. Poor nutrition and genetic vulnerabilities
nary study of acute disease has therefore focused on to M. tuberculosis are secondary (or exacerbating)
the degree of harmfulness (virulence) to which host/ causes of tuberculosis, because tuberculosis can still
parasite associations evolve and the evolutionary func- occur in individuals who have good nutrition or are
tion of disease manifestations – do the manifestations genetically less vulnerable if other conditions such as
increase the evolutionary fitness of the host, the para- immune suppression or intense exposure to M. tuber-
site, both, or neither (Ewald, 1980, 1994). culosis occur. Sometimes more than one category of
A discordance between the evolutionary study of causation must be present for a disease to occur.
acute and chronic disease arises because studies of Cancers for which pathogens are accepted primary
504 Paul W. Ewald
Genetic 29.1. The triad of disease causation. The diagram empha-

sizes joint influences of the three categories of disease caus-
ation. The placement of a disease corresponds to the
relative importance of the three categories with the closest
Cystic
apex indicating the primary cause as defined in the text. The
fibrosis
vertices that are more distant represent exacerbating (i.e.,
secondary) causes or coprimary causes of secondary import-
ance. Cystic fibrosis, for example, is a genetic disease that is
exacerbated by a variety of different pulmonary infections
and low-salt diet. Skin cancer refers to squamous cell skin
Skin cancer ? cancers. The placement of tuberculosis and skin cancer is
Tuberculosis discussed in the text.
Noninfectious
environmental Infectious
causes, for example, generally also require additional lead to several paradoxes that suggest major shortcom-
mutations. In this case environmental mutagens and ings of these explanations. Each of these paradoxes is
the infectious agents are coprimary causes, and the resolved when hypotheses of infectious causation are
cancer would be located roughly equidistant from integrated into the analysis (Ewald, 2008).
the parasitic and environmental vertices. By consider- One paradox arises from variation in the frequency
ing this triangle of causation researchers can avoid of the E4 allele of the APOE gene in humans and other
falling into the trap of failing to consider the validity primates. Its frequency ranges from about 5–40% in
of one category of primary or secondary causation, different human populations (Corbo and Scacchi,
just because the validity of another category has been 1999; Fullerton et al., 2000). Comparisons of nucleo-
identified. tide sequences show that it is the ancestral allele of
The rest of this chapter will apply this perspective Homo sapiens and of primates generally (Fullerton
to specific chronic illnesses that have been discussed et al., 2000) and that its relative frequency has declined
in the literature of evolutionary medicine. I emphasize over the past 200 000 years of human evolution relative
feasible hypotheses of disease causation that have not to the other common alleles, E2 and especially E3
been considered, especially when supportive evidence (Fullerton et al., 2000). The E4 allele therefore is not
exists in the literature. As a result of the bias against an aberrant mutant allele. Some selection pressure in
infectious causation of chronic disease mentioned humans must have disfavored E4 for a long time but
above, the overlooked hypotheses generally involve a differently in different human populations.
failure to consider hypotheses of infectious causation A diet-based hypothesis proposes that rich agricul-
and the interplay between infectious causation and the tural diets are responsible (Corbo and Scacchi, 1999).
other categories of causation. Accordingly, the E4 allele frequency is about 5–15% in
populations with several thousand years of agricultural
experience and about 20–40% in populations that have
Atherosclerosis
been living largely as hunter-gatherers until the twen-
By effecting heart attacks and strokes, atherosclerosis tieth century (Corbo and Scacchi, 1999). These figures
is the leading cause of mortality in the United States indicate that the allele has been declining more rapidly
and other wealthy countries (http://www.cdc.gov/ in agricultural settings. But E4 is a minority allele even
nccdphp/overview.htm). In accordance with its import- among recent hunter-gatherers. The most significant
ance, vast economic and intellectual resources have decline in E4 frequency therefore occurred prior to the
been spent to identify risk factors for atherosclerosis. onset of agriculture.
Dietary constituents have been implicated as exacer- Finch and Stanford (2004) suggest that this shift
bating influences (cholesterol, saturated fats, dietary may have resulted from a shift toward increased meat
iron) and ameliorating influences (unsaturated fats, eating associated with the early evolution of H. sapiens.
omega 3 fatty acids, garlic). The most important Although this timing is consistent with the reduction in
genetic risk factor for atherosclerosis that has been E4 frequencies, it remains an untested hypothesis
identified is the epsilon 4 (E4) allele of the apolipopro- because the change in the makeup of the human diet
tein E (APOE) gene (Ilveskoski et al., 1999; Mahley and during this time is unknown, as is the way in which
Huang, 1999). any such change might alter the role of E4 in lipid
Almost all of the literature on the causes of athero- deposition.
sclerosis in evolutionary medicine attempts to explain The APOE proteins transport fat and cholesterol.
human vulnerability to atherosclerosis in the context Proximate explanations have therefore presumed that
of such vulnerability to genetic and noninfectious the association between E4 and risk of atherosclerosis
environmental risk factors. These analyses, however, results from some difference between E4 and the other
APOE proteins in transport of lipids. But a decade ago, At first glance, the beneficial effects of statins
Gérard et al. (1999) showed that people harboring seems to offer strong support for the cholesterol
the E4 allele were more likely to be infected with the hypothesis, because statins lower serum cholesterol
major candidate infectious cause of atherosclerosis: levels and reduce rates of heart attacks. This reduction
Chlamydophila (Chlamydia) pneumoniae. Recently the in heart attacks, however, was more powerful than
same research group has shown that the E4 protein could be accounted for by the cholesterol-lowering
facilitates attachment of C. pneumoniae to human cells effects of statins (Mays and Dujovne, 2008). Importantly,
(Gérard et al., 2008). The evidence therefore supports statins are associated with reductions in inflammation
the hypothesis that a fitness cost of the E4 allele is and infection-induced mortality in atherosclerosis
increased vulnerability to C. pneumoniae. Unlike the patients (Almog et al., 2007). These findings suggest that
agricultural diet hypothesis, the hypothesis that E4 the beneficial effects of statins may arise not from their
exacerbates atherosclerosis by increasing vulnerability cholesterol-lowering effects, but from anti-inflammatory
to C. pneumoniae is consistent with the timing of the or antimicrobial effects (Jerwood and Cohen, 2008;
evolutionary decline in E4 frequency, so long as Mays and Dujovne, 2008).
C. pneumoniae has been a pathogen of humans throug- Taubes (2008) has pointed out another paradox
hout the evolution of H. sapiens (Ewald and Cochran, of the cholesterol hypothesis. The drug Vytorin® was
2000; Ewald, 2008). The extent to which such a long- approved for lowering the risk of heart attacks based
standing association has occurred should be testable on its cholesterol-lowering effects. These effects arise
using molecular phylogenetic reconstructions of from the two active components of Vytorin®. The first
Chlamydophila. The hypothesis that a shift toward an component is a statin called Zocor®. The second is a
atherosclerosis-inducing diet occurred early during drug, called Zetia®, which lowers cholesterol by a dif-
the evolution of H. sapiens is also consistent with this ferent mechanism. The addition of Zetia® to Zocor®
early shift away from E4 (Finch and Stanford, 2004), was approved because it lowered cholesterol more than
but this hypothesis will be more difficult to test. Unlike Zocor® alone. The addition of Zetia®, however, did not
the infectious causation hypothesis, this early sapiens lower the risk of heart attacks more than Zocor® alone.
diet hypothesis does not have empirical support from Taubes (2008) rightly points out that this finding serves
a proximate pathogenic mechanism, because we do as a critical test of the cholesterol hypothesis and that
not know whether the diet of early H. sapiens involved the cholesterol hypothesis failed the test.
a shift toward constituents that fostered atheroscler- These considerations suggest that the paradoxes
osis. This argument illustrates the need for a broader over the role of cholesterol resulted from premature
consideration of alternative hypotheses in evolutionary acceptance of a reasonable hypothesis rather than a
medicine, because the proponents of the early sapiens more comprehensive consideration of the evidence in
diet hypothesis made no reference to the possibility the context of the full range of feasible hypotheses.
that C. pneumoniae could be responsible for the Integrating hypotheses of infectious causation resolves
reduction in the E4 frequency (Finch and Stamford, these paradoxes, by revealing that the incongruous
2004; Finch, 2007; Austad and Finch, 2008), even findings are consistent with a more cohesive theory
though the vulnerability of E4 individuals to C. pneu- of pathogenesis. The accumulation of cholesterol
moniae and the relevance of this vulnerability to ath- within the walls of arteries, for example, is prece-
erosclerosis has been in the literature for about a ded by the accumulation of cholesterol-laden macro-
decade (Gérard et al., 1999, Ewald, 2000; Ewald and phages, called foam cells, within the arterial walls
Cochran, 2000). (Crowther, 2005). Chlamydophila (Chlamydia) pneumo-
Another paradox concerns the widely accepted niae can infect macrophages and transform them into
hypothesis that cholesterol is a cause of atheroscle- foam cells by fostering the uptake of fat and choles-
rosis. Cholesterol accumulates within arterial walls terol. Zetia® may fail to decrease cardiovascular events
early during the pathogenesis of atherosclerosis because elevated serum cholesterol is a correlate and
(Crowther, 2005). When it was thought that this accu- perhaps a minor exacerbating cause of these events
mulation was on the inside surface of the arteries it rather than a primary cause.
was reasonable to hypothesize that high cholesterol A similar resolution applies to dietary components
diets would lead to high levels of cholesterol in the that appear to reduce the risk of heart attacks. Con-
blood, which in turn would lead to higher deposition sider garlic. Over the past two decades, investigations
of cholesterol. The link between elevated serum choles- of apparently beneficial effects of garlic on atheroscle-
terol and deposition of cholesterol within the arterial rosis have focused almost entirely on alterations of
walls is less convincing, but the elevated cholesterol lipids by a component of garlic: allicin. But published
hypothesis can still be rescued if the cholesterol is studies have not documented consistent associations.
somehow selectively transported to sites within arterial Recently the controversy was largely put to rest by the
wall without being deposited on the lining of arteries. most thorough study yet on the relationship between
506 Paul W. Ewald
garlic and lipid composition, which showed no signifi- arguments tend to implicate the mismatch between
cant effects (Gardner et al., 2007). The results of this ancestral and modern environments. It is argued, for
study may be invoked by some to dismiss the hypothe- example, that the increased life spans of modern
sized beneficial effects of garlic against atheroscler- humans increases the prevalence of cancer because
osis. Yet the results of that study were predicted by cancers tend to occur during the later decades of life.
a hypothesis that invokes the antibiotic effects of The proximate part of this argument focuses on the
garlic instead of a lipid-altering effect (Ewald, 2008). greater chance for the accumulation of oncogenic
This antibiotic hypothesis has not yet been specifically mutations and disregulation of cellular processes as
tested because researchers have been so narrowly life span increases; the evolutionary part focuses on
focused on the lipid hypothesis of atherosclerosis the weakness of natural selection to counteract cancers
pathogenesis. Studies of the role of garlic on athero- that occur late in life (Greaves, 2000). To explain why
sclerosis need to take a more balanced approach by genetic predispositions to cancer might be spreading in
investigating the possibility that garlic may ameliorate human populations, evolutionary hypotheses raise the
atherosclerosis by inhibiting pathogens that are impli- possibility that the genetic predispositions are alleles
cated as primary causes of atherosclerosis. that have been favored recently in human evolution
Unlike the other hypotheses that have been pro- and an that increased cancer risk has tagged along as
posed to explain the atherosclerosis, the infectious a pleiotropic cost (Crespi and Summers, 2006).
hypotheses of atherosclerosis do not generate such Analyses of oncogenesis in evolutionary medicine
interpretive paradoxes. Moreover, predictions of the focus on environmental mutagens and inherited pre-
infectious causation hypothesis have been confirmed dispositions (Crespi and Summers, 2005; Merlo et al.,
by the most direct tests: the presence of C. pneumoniae 2006; Frank, 2007; Greaves, 2008; Komarova and
and other pathogens in the foci of disease, elevated Wodarz, 2008). A testament to this oversight is found
positivity in afflicted patients, and mechanisms that in the most comprehensive text of biological topics in
link infection with the other risk factors in a causal evolutionary medicine (Stearns and Koella, 2008),
network (e.g., C. pneumoniae fostering foam cell where cancer is included in the section on “Noninfec-
formation in early stages of atherosclerosis, and E4 tious and degenerative diseases,” even though infec-
increasing vulnerability to C. pneumoniae; see Ewald tious causation can be definitively ruled out for only a
and Cochran, 2000 and Ewald, 2008 for more details). miniscule proportion of human cancer. When infec-
These considerations of atherosclerosis illustrate tions are considered (Greaves, 2000, 2006), infection
the value of using the triangle of causation as a basis has not been integrated with mutation, and inheritance
for analyzing disease causation. The evidence pertain- into a unified theory of oncogenesis.
ing to E4 illustrates how paradoxes associated with the As was the case with peptic ulcers and atheroscler-
most important genetic vulnerability to atherosclerosis osis, considerations of cancer within evolutionary
are resolved when the analysis is broadened to include medicine has been lagging behind rather than advan-
the infection vertex. The evidence pertaining to choles- cing demonstrations of infectious causation. Over the
terol shows how paradoxes associated with one of the past 30 years a major trend in the understanding of
most widely incriminated dietary agents of atheroscler- oncogenesis has been recognition of an increasing role
osis are resolved when the analysis includes infection. for infectious causes of cancer, mirroring the trend for
The evidence pertaining to garlic shows how an ameli- chronic diseases in general (Ewald, 2009). In the mid
orating environmental influence could be inappro- 1970s unicellular or subcelluar parasites were gener-
priately rejected because the spectrum of hypotheses ally accepted as a cause of only one human cancer:
under consideration was inappropriately narrow. In Burkitt&s lymphoma, which is caused by simultaneous
each case evolutionary considerations are useful in gen- infection of Epstein–Barr virus and Plasmodium falci-
erating and evaluating alternative causal explanations. parum. With regard to multicellular parasites, some
trematodes were recognized as contributing to liver
and bladder cancer. The total amount of cancer
Cancer
accepted as being caused by parasitism was therefore
Cancer is characterized by the pathological prolifer- less than 1% of all human cancer. Over the past three
ation and systemic spread of cells. It is widely accepted decades, this percentage has increased steadily. Now
that cancers result primarily from mutations that about 20% of all human cancer is accepted by the
promote cell proliferation and inhibit cell adhesion World Health Organization as being caused by parasit-
(leading to metastasis). Consequently, researchers ism. Although overviews of cancer often presume that
writing from an evolutionary perspective have attem- the remaining 80% are caused by something other than
pted to explain why the human body is vulnerable to parasitism, this conclusion is not justified by the evi-
such mutation-induced disregulation of proliferation dence. Because all three categories of disease caus-
and adhesion. As is the case with atherosclerosis, ation may act in concert, identification of a cause in
one category cannot be used as evidence that any other cancer. Rather, the breakdown of the barriers to cancer
category is invalid. The documented importance of favor persistence within the host but nudge infected
inherited predispositions, environmental mutagens, cells toward cancer. An infection with any of the known
and the genes they mutate therefore does not imply oncogenic viruses is by itself insufficient to cause
that infectious agents are playing no causal role. human cancer, because only a small proportion of the
This idea is well illustrated by skin cancer. There is people who are infected with any one of these viruses
general agreement that ultraviolet rays contribute to skin will develop cancer. Other causes must therefore
cancer (Greaves, 2000; Kleinsmith, 2005; Karagas et al., contribute.
2007). One inherited genetic vulnerability for skin Consideration of breast cancer offers an illustra-
cancer is low amounts of protective skin pigment tion of the need for an integrated approach to oncogen-
(Greaves, 2000, Kleinsmith, 2005). This vulnerability esis. The most widely accepted evolutionary explanation
can be attributed largely to a mismatch between ances- for breast cancer has been advanced by Boyd Eaton and
tral and modern environments – the ancestry of people his colleagues (Eaton et al., 1994; Eaton and Eaton, 1999;
with light skin color can be traced to northern latitudes, Greaves, 2008; Stearns et al., 2008; Trevathan et al., 2008).
where exposure to ultraviolet radiation has tended to be This explanation, which can be labeled the hormonal
low. Light skinned people tend to have high cancer rates proliferation hypothesis, focuses on oncogenic effects of
when they live in more southerly environments with estrogen and, to a lesser extent, progesterone. It proposes
higher exposure to ultraviolet radiation. Both evolution- that elevated rates of breast cancer in economically
ary and proximate analyses of the causes of skin cancer wealthy societies may result from enhanced cyclic expos-
have been largely restricted to these two categories with ure to these hormones.
little consideration of infectious causation. Yet evidence The hormonal proliferation hypothesis points out that
implicating nongenital serotypes of human papilloma- estrogen and perhaps progesterone contribute to the
virus (HPV) as a cause of squamous cell skin cancer has proliferation of cells in breast tissue (Potten et al., 1988)
been published over the past decade. The evidence is and attributes elevated rates of breast cancer in modern
particularly strong for people with suppressed immunity societies to a mismatch between modern and ancestral
and the rare hereditary skin disease epidermodysplasia environments. It proposes that the mismatch results from
verruciformis, and probably involves disregulation of modern birth control and modern diets. Birth control
control over cellular division (Jenson et al., 2001; Karagas increases the number of menstrual cycles during a life-
et al., 2006; Andersson et al., 2008). These considerations time because women do not cycle during pregnancy and
suggest that HPVs may be coprimary causes or exacer- much of lactation. Rich diets apparently increase the
bating causes of squamous cell skin cancer (hence the number of cycles by advancing menarche and delaying
arrow with the question mark in Figure 29.1). Consider- menopause. Studies within post-industrial societies show
ing only epidermodysplasia verruciformis and HPV the that women who begin menstruation at younger ages and
evidence supports a central location in the diagram. end menstruation at older ages have higher risks of breast
Cells have four critical barriers to cancer. Cell cycle cancer than women whose menstrual cycles occur over
arrest keeps the cell from dividing. Apoptosis (cell suicide) a more restricted range of years (Key and Pike, 1988;
can destroy proliferating cells before they progress to Trichopoulos et al., 1996). As a result of these differences,
metastatic cancer. Restriction of telomerase can block Eaton et al. (1994) estimate that women in the United
oncogenesis by placing an upper limit on the total States have nearly three times as many menstrual cycles
number of divisions that a cell lineage undergoes. Cell during their lifetimes as women in hunter-gather soci-
adhesion prevents metastasis. eties. They estimate that US women have about 100 times
Some viruses have evolved intricate mechanisms to more breast cancer.
interfere with these barriers, apparently to foster per- As Eaton and his colleagues note, the risk of breast
sistence of the viruses within their hosts. By causing cancer is greater during pregnancy (Bruzzi et al., 1988;
the cells that they infect to divide, the genetic material Williams et al., 1990). The increased risk persists during
of a virus can replicate in concert, while incurring little the first year after childbirth and declines gradually
exposure to the immune system. By interfering with thereafter. Prior to menopause the declining risk of
apoptosis the virus can keep the cell from destroying breast cancer with increasing time since last birth
the virus via cell suicide. By increasing telomerase approaches but does not drop below that of nulliparous
activity, the virus can push the infected cell toward women (Bruzzi et al., 1988; Williams et al., 1990; Lambe
immortality, perpetuating this profitable exploitation et al., 1994). Protection associated with a greater number
of the host cell for both resources and protection. By of births was significant only for women in their 40s
interfering with cell-to-cell adhesion, infected cells can (Bruzzi et al., 1988; Williams et al., 1990). These associ-
spread to other parts of the body to facilitate further ations raise a paradox if one assumes that pregnancy
viral proliferation and transmission. This argument protects against breast cancer: no protective effect of
does not suggest that pathogens benefit from lethal pregnancy is apparent after birth among premenopausal
508 Paul W. Ewald
women. To the contrary, parous women have greater risks proliferation. But this reduced control of proliferation
of premenopausal breast cancer than nulliparous women would have to occur after menopause but not detectably
of the same age, but lower risks of cancer during the before menopause.
decade of life in which menopause generally occurs. The protective association with parity for postmeno-
Eaton and his colleagues accommodate this paradox by pausal breast cancer and the exacerbating association of
restricting their hypothesis to postmenopausal breast parity prior to menopause is a paradox that needs to be
cancer. At best this restriction leaves much of the elevated resolved by a general theory of breast cancer. If parity
breast cancer in post-industrial societies – that occurring protects against breast cancer, why does it protect only
premenopausally – without an adequate evolutionary after menopause? Higher rates of estrogen during preg-
explanation. nancy may play a role, but the paradox is not resolved
The restriction of the hormonal proliferation by direct effects of estrogen on proliferation rates,
hypothesis to postmenopausal breast cancer raises because a large proportion of these cancers do not
another paradox. How can the proliferative effects of express the receptors for estrogen and progesterone. Also,
estrogen cause increased cancer rates only after estro- the persistence of elevated breast cancer risk during the
gen levels have declined? Cognizant of this paradox, first year after parturition is not explainable as a direct
Eaton and Eaton (1999) conclude that the main onco- effect of estrogen, because estrogen levels decline within
genic effects of estrogen result from effects of prolifer- a week or so after pregnancy (Doyle et al., 2007).
ation on mutation rather than the nudging of Consideration of infectious causation resolves
proliferation higher. This resolution represents a major these paradoxes. An immune suppression/infection
restriction of the estrogen proliferation hypothesis to hypothesis proposes that infectious agents may act in
the proliferative effects on mutation, thus abandoning concert with mutations and inherited predispositions
any direct contribution of hormone-induced prolifer- to cause breast cancer. It does not deny the potential
ation on the runaway proliferation that characterizes applicability of estrogen and progesterone. But rather
cancer. than focusing on the proliferative effects of these hor-
Another paradox arises because protection against mones, it emphasizes their suppressive effects on cell
peri- and postmenopausal breast cancer appears to be mediated immunity (Doyle et al., 2007, 2008), which
associated with pregnancies during the first decade or may increase vulnerability to persistent viruses.
so after menarche. Eaton and Eaton (1999) resolve Three persistent viruses have been strongly associ-
this paradox by assuming that the relevant prolifer- ated with breast cancer: Epstein–Barr virus (EBV),
ation is occurring restricted to this time period. As a HPV (particularly serotypes 16 and 18), and mouse
result of earlier menarche, women in post-industrial mammary tumor virus (MMTV; human isolates are
societies have more menstrual cycles prior to first generally referred to as MMTV-like). Each of these
pregnancies than women in hunter-gatherer societies, viruses is found in about 25–50% of breast cancers but
and thus may have more breast cell proliferation that in less than about 10% of the normal breast tissue from
could predispose them to a greater incidence of breast the same patients (Wang et al., 1995; Bonnet et al., 1999;
cancer. However, because the elevated rates of breast Fina et al., 2001; Lawson et al., 2001; Kleer et al., 2002;
cancer in post-industrial societies generally occur Damin et al., 2004; Kan et al., 2005; de Villiers
postmenopausally, decades after this proliferation, et al., 2005). Each virus stimulates proliferation of
the proliferation itself does not seem to be causing infected cells and inhibits apoptosis (Subramanian and
breast cancer directly by nudging up proliferation Robertson, 2002; Katz et al., 2005; Knight et al., 2005;
rates. Eaton and his colleagues therefore suggest that Mileo et al., 2006; Guasparri et al., 2008; Hino et al.,
the mechanism by which proliferation increases 2008). Both EBV and HPV are also known to promote
cancer is mainly through increased mutation prior to cellular immortalization by enhancing telomerase activ-
the first birth. ity (Ding et al., 2007; Liu, 2008; Tungteakkhun and
After menopause proliferation of breast cells is twice Duerksen-Hughes, 2008; investigations of effects of
as great for nulliparous women than for parous women. MMTV on telomerase activity have not yet, to my know-
But this difference does not accord well with the ledge, been conducted).
hormonal proliferation hypothesis, because women are Each of these viruses interferes with cell-to-cell adhe-
not experiencing the elevated levels of estrogen after sion, thereby promoting metastasis. Expression of the
menopause. Nor does this difference accord with the cellular adhesion molecule, nm23H1, declines as breast
histological changes that are associated with parity, and other cancers progress to lethal metastatic out-
because at menopause breast cell types revert to the com- comes (Branca et al., 2006; Mileo et al., 2006; Sgouros
position found in nulliparous woman (Russo, 1992). et al., 2007). The MMTV inhibits expression of the
One can save the hormonal proliferation hypothesis by nm23H1 (Ouatas et al., 2002) and EBV inhibits the abil-
arguing that mutations that occur soon after puberty ity of nm23H1 to suppress cell migration (Subramanian
are particularly associated with reduced control of and Robertson, 2002; Murakami et al., 2005). Human
papillomavirus downregulated and inactivated nm23H1 such pathogens because women who are raising families
in keratinocytes (Mileo et al., 2006). In a study using tend to have fewer sexual partners than single women.
esophageal cells, HPV16 did not inhibit nm23H1 but Moreover, nulliparous women may be nulliparous
did inhibit a different cellular adhesion molecule, because they have had a relatively high exposure to
CD44v6 (Liu et al., 2005), decreased levels of which are sexually transmitted pathogens which can reduce fertil-
associated with progression to metastatic cancer (Maula ity (as is the case with Chlamydia trachomatis and
et al., 2001). Neisseria gonorrheae).
Whether any one of these viruses must act with any The immune suppression/infectious hypothesis
other to generate cancer is unknown. These associations predicts a temporal pattern of mutations that is not
could therefore explain anywhere from about half to predicted by the hormonal proliferation hypothesis.
nearly 100% of human breast cancer. Regardless of this Specifically, if simultaneous inhibition of the cancer
number, evidence indicates that any oncogenic action of barriers by viruses is needed to initiate oncogenesis,
these viruses occurs together with oncogenic mutations, the additional mutations of barriers to cancer should
because oncogenic mutations are found in a substantial tend to occur later during oncogenesis. In contrast the
proportion of breast cancers. But consideration of the hormonal proliferation hypothesis proposes that such
interdependence of the different steps of oncogenesis mutations are initiating events and should therefore
suggests that viral sabotaging of barriers to cancer gener- often at the onset of oncogenesis.
ally occurs before oncogenic mutations. Activation of This prediction is testable, as illustrated by a
cell replication without inhibition of cellular senescence, recent study (Saal et al., 2008) of a gene referred to as
for example, would have low oncogenic potential because PTEN (for Phosphatase and TENsin homolog) in
it would generate only a limited number of cellular women who have inherited an mutation in a breast
divisions. Similarly, inhibition of cellular senescence cancer susceptibility gene called BRCA1 (for BReast
would be of limited value without inhibition of apoptosis, CAncer susceptibility gene type 1). The PTEN gene
which would have the potential of destroying the infected fosters cellular replication and inhibits apoptosis. The
cell. Without infectious causation, a specific sequence BRCA1 gene encodes a protein that repairs mutations.
of very specific mutations would have to compromise Mutations in the BRCA1 gene therefore contribute to
these barriers without destroying the cell&s viability. cancer by reducing the repair of mutations in other
In contrast, infection by the three viruses mentioned genes that encode barriers to cancer, and women who
above typically inhibit three or four of the key barriers inherit a mutant BRCA1 allele have a higher net rate
to metastatic cancer simultaneously. This simultaneous of mutation in their somatic cells. Understanding
inhibition would allow each infected cell to generate large the function of these two genes led researchers to
numbers of infected cells through cellular replication. expect that women with the BRCA1 mutation would
Once large numbers of precancerous cells are generated, be susceptible to PTEN mutations, which could then
the standard arguments about cancer evolution would lead the mutated cells down the path to cancer. PTEN
apply: additional oncogenic mutations that further mutations do tend to occur in the breast cancers. But
inhibit these barriers or other barriers to cancer would in contrast with the expectations of researchers study-
favor evolution of subsets of the precancerous cells ing this association, PTEN mutations occur late during
toward cancer. Even if large numbers of precancerous oncogenesis, as expected if viral infection initiates
cells in this population of precancerous cells lose their oncogenesis and mutations complete the process after
viability because of damaging mutations, oncogenesis a sufficiently large population precancerous cells has
can continue because many other infected cells remain become established.
to generate additional oncogenic mutations. This example illustrates how hypotheses of infec-
The immune suppression/infection hypothesis offers tious causation of cancer can be broadly distinguished
resolutions of the paradoxes raised by the hormonal from hypotheses that rely solely on mutation. Infections
proliferation hypothesis. The elevated risk of breast will be found early during oncogenesis, but oncogenic
cancer during pregnancy may result from effects of the mutations will not be found in the earliest stages.
elevated reproductive hormones on the part of the Because infection initiated cancers still depend on
immune system that controls virally infected cells. This mutations for cancer progression evidence that broadly
effect might occur synergistically with any hormonal implicates oncogenic mutation (e.g., age dependent
enhancement of the proliferation of infected cells. The risks of cancer; Frank, 2007) are consistent with infec-
associations with parity can be explained by effects of tion-initiated oncogenesis. But despite this consistency
mate fidelity and duration of sexual activity on exposure the distinction between mutation-only hypotheses and
to infection. Women who begin menses earlier will tend infection-initiated hypotheses is critical because the
to have a longer exposure to sexually transmitted patho- infection-initiated hypotheses suggest that cancers
gens such as HPV and kissing transmitted pathogens can be prevented by preventing infection. The great
such as EBV. Having children may reduce exposure to practical benefit from cancer prevention relative to
510 Paul W. Ewald
cancer treatment emphasizes the importance of testing seem to be a particularly difficult evolutionary hurdle.
the central prediction from the infection-initiated Natural selection would favor regulation of the response
hypothesis, namely that infectious agents tend to be so that women gain the protective benefits without
present and oncogenic mutations absent during the risking death. Although it is appropriate to consider the
earliest phases of oncogenesis. overzealous response hypothesis, it certainly should not
be accepted without testing, especially when other more
compelling hypothesis have not been considered or
Pregnancy sickness
tested.
In some chronic diseases the failure to consider Consideration of infectious causation offers such
infectious causation has led to study of hypotheses that an alternative hypothesis. Among infectious diseases
may explain the baseline occurrence of a phenomona, one frequently finds manifestations that sometimes func-
but not the most damaging occurrences. Pregnancy tion as a defense but can be disregulated by infectious
sickness offers an example. Pregnancy sickness, also agents to such an extent that host death ensues. Diarrhea,
called “morning sickness,” is a sensation of nausea that for example, is known to facilitate the recovery by
is particularly common during the first trimester of expelling the causal pathogens – suppression of diarrhea
pregnancy. Evolutionary considerations suggest that in patients experimentally infected with the diarrhea-
debilitating nausea would be selected against if it did causing pathogen, Shigella sonnei, prolonged recovery
not provide a compensating fitness benefit. from infection (Dupont and Hornick, 1973). When
Hook (1976), Profet (1992), and Flaxman and Sher- humans are infected with Vibrio cholerae, however, the
man (2000) developed the hypothesis that pregnancy diarrhea-induced dehydration is as a rule the cause of
sickness is an adaptation that reduces ingestion of death. Unlike S. sonnei, V. cholerae does not invade the
noxious agents (toxins and pathogens) and thereby intestinal lining. Moreover, because V. cholerae is a strong
protects the developing embryo and the expectant swimmer and can adhere to the lining of the small intes-
mother. Such noxious agents tend to be dangerous or tine, it can persist in the intestine in the face of the rapid
indicators of dangerous substances within food. Nausea fluid movements associated with diarrhea. In fact,
in response to the smell or taste of secondary compounds V. cholerae induces the diarrhea by releasing a toxin
may therefore cause the avoidance or regurgitation of that attaches to the cells that line the small intestine.
toxin-laden and microbially contaminated foods. Fetal This attachment results the entrance of part of the toxin
damage during the first trimester of pregnancy could molecule into the cell, which eventually leads to the
have marked consequences because damage to small cell&s release of fluid into the lumen of the intestine.
numbers of cells early during development may cause The resultant diarrhea washes out competing bacteria
substantial damage to tissues or organs that develop from from the entire intestinal tract. Strains of V. cholerae that
those cells, leading to birth defects or miscarriages. produce large amounts of toxin thus produce a watery
Heightened nausea in response to secondary chemicals fecal material with large numbers of V. cholerae and few
in food may protect developing embryo and fetus from other micro-organisms. This watery Vibrio-laden stool
such damage. This hypothesis is supported by the timing can broadly contaminate the external environment,
of symptoms during pregnancy and reduced risks of fostering transmission to other humans. For V. cholerae
miscarriage among women experiencing pregnancy the generation of diarrhea is thus a sometimes lethal
sickness (Profet, 1992; Flaxman and Sherman, 2000). manipulation (sensu Ewald, 1980) of what is often a
This fetal protection hypothesis, however, raises a defensive response for its own benefit (summarized from
paradox. Sometimes the vomiting associated with Ewald, 1994).
pregnancy sickness is so severe that women will die of Consideration of infectious causation therefore
dehydration. One would not expect natural selection to raises the possibility that a similar hypothesis might
favor lethal nausea as a defense against damage that is resolve the paradox of lethal pregnancy sickness.
much less costly to fitness. When such paradoxes are Specifically, it suggests the possibility that an infec-
addressed in the literature of evolutionary medicine, they tious organism could manipulate the nausea defense,
are often explained away by the weakness of natural exacerbating it to the point that it may cause life-
selection. Specifically, it is argued that natural selection threatening dehydration. Helicobacter pylori is a
is too weak to eliminate the damaging effects of an logical candidate for such an organism because it
overzealous response, which might be maintained in the infects the lining of the stomach and regurgitation
population as a result of the positive effects of a much would provide one of the most direct transmission
more common, controlled response. This overzealous routes. Epidemiological evidence implicates this
response hypothesis is not compelling because maternal route (Perry et al., 2006), as well as transmission from
death seems like too great a price to reduce exposure of mother to offspring (Sinha et al., 2004; Yang et al.,
babies to the secondary compounds in food and because 2005, Delport and van der Merwe, 2007) and wife to
control of nausea below life-threatening levels does not husband (Fujimoto et al., 2007).
TABLE 29.1. Illnesses of uncertain cause, their associations with infection, and publications within evolutionary
medicine that did not consider infectious causation of the specified illness.
Causal hypothesis presented in Infectious agent or

Illness evolutionary medicine literature infectious disease Publications
Skin cancer Ultraviolet radiation, light skin color HPV Greaves (2000*, 2008*)
Breast cancer Increased menstrual cycling MMTV, EBV, HPV Eaton et al. (1994)
Eaton and Eaton (1999*)
Pre-eclampsia Parent–offspring genetic conflict Periodontitis, urinary Haig (1993, 2008*)
tract infection
Pregnancy sickness Protection from dietary mutagens Helicobacter pylori Profet (1992); Sherman and
Flaxman (2002*)
Schizophrenia Mutations and environmental stress Toxoplasma gondii Nesse and Stearns (2008*);
Trevathan et al. (2008*)
Atherosclerosis Rich diet and lipid transport of APOE4 Chlamydia pneumoniae Nesse and Williams (1995*)
Gerber and Crews (1999*)
Finch and Stanford (2004*)
Alzheimer&s disease Immunological correlates and Chlamydophila Nesse and Williams (1995)
(nonfamilial) compensating benefits of APOE4 (Chlamydia) Austad (1997), Finch (2007*)
pneumoniae Austad and Finch (2008*)
Note: *Signifies works that were published after the infectious link to the illness was published. EBV, Epstein–Barr virus; HPV, human
papillomavirus; MMTV, mouse mammary tumor virus.
Investigations of associations between H. pylori and but rather emphasizes conditions that have been
severe pregnancy sickness have generated mixed results. considered often in the literature on evolutionary
About halfof thestudiesdocument significant associations medicine or pose major unsolved health problems.
(Koçak et al., 1999; Reymunde et al., 2001; Kazerooni et al., The pathogens implicated are not yet broadly accepted
2002; Cevrioglu et al., 2004; Shirin et al., 2004; Karaer et al., as causes of the listed conditions, even though strong
2008) and about half do not (Wu et al., 2000; Berker evidence of infectious causation exists.
et al., 2003; Jacobson et al., 2003; McKenna et al., 2003; Discussion of schizophrenia in evolutionary medicine-
Weyermann et al., 2003; Lee et al., 2005). This discrepancy literature (e.g., Nesse and Stearns, 2008), generally
may result from differences in the strains in different has not incorporated the increasingly strong evidence
populations of study subjects. In a study of 143 pregnant of infectious causation (Ledgerwoood et al., 2003;
Turkish women (Noyan et al., 2004) the elevated positivity Brown et al., 2004; Crespi et al., 2007; Hinze-Selch
for H. pylori among dyspepsic women (75% vs. 64%) was et al., 2007; Mortensen et al., 2007; Niebuhr et al.,
not statistically significant. But among those women 2008). Longstanding claims of genetic causation based
who tested positive for H. pylori, those who complained on familial studies have been accepted even though
of dyspepsia were significantly more often infected with these associations can be explained by in utero infec-
strains possessing a major virulence determinant – the tious causation (Ledgerwoood et al., 2003). Specific
cytotoxin-associated gene A (66% vs. 34%). genetic associations generally explain only vanishingly
Taken together these results suggest that some small proportions of schizophrenia. If primary causes
strains of H. pylori may facilitate their own transmis- of schizophrenia are largely infectious we can expect
sion by exaggerating a nausea response that evolved to that the most common genetic predispositions to
protect the fetuses of uninfected women. As is the case schizophrenia will tend to be vulnerabilities to such
with V. cholerae, the conflict of interest between infectious causes (Ledgerwood et al., 2003). Accordingly
H. pylori and its human host may sometimes lead to one of the strongest genetic associations identified to
death through dehydration. date was recently found to encode an interleukin recep-
tor, even though the researchers were not searching for
a gene associated with the immune system and con-
IMPLICATIONS FOR EVOLUTIONARY sidered this association surprising (Lencz et al., 2007).
MEDICINE Pre-eclampsia is that occurs in about 3% of preg-
nancies (Conde-Agudelo et al., 2008). In the evolution-
Table 29.1 lists several other chronic illnesses of uncer- ary medical literature explanations of pre-eclampsia
tain cause that have been discussed in the literature have been almost entirely restricted to genetic conflicts
of evolutionary medicine. The list is not exhaustive, between mother and fetus (Haig, 1993, 2008). Yet a
512 Paul W. Ewald
large literature on associations between infection and drawing evolutionary interpretations of the current
pre-eclampsia has accumulated. Particularly reliable often incorrect consensuses? If evolutionary medicine
are the associations between pre-eclampsia and follows the latter route, it is destined to present inter-
both periodontal disease, which is caused largely by pretations that are faulty because they are based on
Porphyromonas gingivalis, and urinary tract infection the faulty consensuses.
(Conde-Agudelo and Belizan, 2000; Conde-Agudelo Taking the lead on these issues also offers the
et al., 2008; Siqueira et al., 2008). promise of practical benefits. If infectious causation is
A thorough evolutionary examination of pre-eclampsia more pervasive than is currently accepted by modern
needs to resolve the maternal–fetal hypothesis with medicine and evolutionary biology expedites the recogni-
these infectious associations. Analyses need to consider tion of this pervasiveness then it will also expedite the
whether there is any evidence implicating infectious recognition of ways to prevent these diseases. In many
causation that cannot be explained by maternal–fetus cases the practical benefits are obvious. Prevention of
conflict and vice versa. Similarly, analyses need to chronic diseases such as cancers, heart attacks, and
consider whether the two categories of causation are strokes, would provide vast health benefits because such
both acting and perhaps interacting. Both categories chronic diseases are the major sources of mortality in
of hypotheses need to be considered in light of other economically prosperous countries. It is reasonable to
risk factors (Conde-Agudelo and Belizan, 2000) to expect that such diseases could be prevented, for
address key characteristics of pre-eclampsia, such as example, by vaccination because the track record of the
its relatively low prevalence, greater damage in poor health sciences at controlling or preventing infectious
countries, and associations with parity. diseases has been very strong.
The understanding of nonfamilial Alzheimer&s A broadened perspective within evolutionary medi-
disease parallels that of atherosclerosis. Chlamydo- cine also provides more subtle insights into how dis-
phila (Chlamydia) pneumoniae has been identified eases should be treated. Recognition that pregnancy
in a large portion of Alzheimer&s disease patients sickness may often protect fetal development suggests
(Balin et al., 1998). The association of E4 with Alzhei- that the symptoms of pregnancy sickness may often be
mer&s disease and the vulnerability to C. pneumoniae best left untreated, but this suggestion does not apply to
infection conferred by E4 indicates that C. pneumoniae symptoms that could cause life-threatening dehydra-
is probably a cause of sporadic Alzheimer&s disease. Yet tion (Flaxman and Sherman, 2000). Without consider-
evolutionary discussions of Alzheimer&s disease generation of infectious causation, evolutionary medicine
ally do not integrate the evidence implicating C. pneumo- may not be able to specify the boundary between appro-
niae (Finch, 2007; Austad and Finch, 2008). priate and inappropriate treatment. If, however,
Without consideration of infectious causation the H. pylori is responsible for the life-threatening symp-
relative roles of infectious causation, inherited genes, toms of pregnancy sickness, this difficulty may be
and noninfectious environmental risk factors cannot resolvable. The evolutionarily informed advice would
be ascertained. Because the value of the evolutionary be for women to be tested for H. pylori and treated with
explanations depends on the validity of the proximate antibiotics if the test comes back positive. Ideally this
causes that they are attempting to explain, a failure to testing should be done prior to pregnancy to avoid any
consider the full spectrum of the proximate causes raises negative effects of the antibiotics on fetal development.
concern about the validity of the evolutionary explan- Once H. pylori is eliminated, symptoms of pregnancy
ations. If such diseases are caused largely by infection, sickness should be ameliorated.
evolutionary explanations that do not incorporate infec- Medicine has developed largely without a funda-
tious causation will be largely incorrect. This problem mental theoretical framework. This situation has made
is particularly important if infectious causation is intim- medicine vulnerable to the predispositions that are
ately related to genetic causation and noninfectious present among the majority of experts at any given time.
environmental causation, as appears to be the case with From the early nineteenth century onward these predis-
breast cancer and atherosclerosis. If, for example, the positions have involved the unwarranted rejection of
primary role of E4 in atherosclerosis is to increase the infectious diseases. Decade by decade new categories
infection rate of C. pneumoniae then the attempts to of diseases have been gradually added to the spectrum
explain the association between E4 allele and atheroscler- of infectious disease. Over the past half century this
osis or Alzheimer&s disease strictly in terms of transport trend has continued with chronic diseases such as
of lipids are futile. peptic ulcers, cervical cancer, and liver cancer being
Much is at stake. Will evolutionary medicine lead recognized as infectious diseases. Infectious causation
the health sciences to better understandings of med- of diseases such as breast cancer, atherosclerosis,
ical issues and new discoveries? Or will it simply and schizophrenia are on the threshold of acceptance.
follow circuitous routes dictated by the biases of Evolutionary medicine is uniquely positioned to
nonevolutionary medicine at any particular time, advance these trends because, unlike other areas of
medicine, it is inclusive of all areas of medicine. It seeks valuable discussions on the topic. Holly A. Swain Ewald
to integrate conceptually all proximate and ultimate first drew my attention to viral disruption of cellular
explanations of health and disease. Molecular, bio- adhesion molecules, and has provided broadly insightful
chemical, cellular, developmental, morphological, and suggestions throughout the development of this work.
physiological processes provide the evidence on which
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30 Beyond Feast–Famine: Brain Evolution,
Human Life History, and the Metabolic
Syndrome
Christopher W. Kuzawa
EXPLAINING THE MODERN METABOLIC 2008). The idea that obesity and related diseases result
DISEASE EPIDEMIC: THE THRIFTY GENOTYPE from a “discordance” or “mismatch” between our
HYPOTHESIS AND ITS LIMITATIONS ancient genes and our rapidly changing lifestyle and
diet is now widely accepted, and it seems clear that
Today, more than 1 billion people are overweight or obesity must be more common today in large part
obese, and the related condition of cardiovascular dis- because we are eating more and expending less than
ease (CVD) accounts for more deaths than any other our ancestors traditionally did (Eaton and Konner,
cause (Mackay et al., 2004). Why this epidemic of 1985; see Chapter 28 of this volume). Despite the intui-
metabolic disease has emerged so rapidly in recent tive appeal of these ideas, the hypothesis is not without
history is a classic problem for anthropologists con- limitation. For one, it helps explain why we gain weight
cerned with the role of culture change in disease in a modern environment of nutritional abundance,
transition (Ulijaszek and Lofink, 2006). In 1962, the but says very little about the syndrome of metabolic
geneticist James Neel proposed an explanation for this changes that account for the diseases that accompany
phenomenon that looked for clues in the “feast– obesity (Vague, 1955; Kissebah et al., 1982). While
famine” conditions that he believed our nomadic, for- excess weight gain in general is unhealthy, it is specif-
aging ancestors faced in the past. Given the unpredict- ically fat deposition in the visceral or abdominal region
ability of food resources in natural ecologies, Neel that accounts for the bulk of its adverse effects on
suggested that a “thrifty” metabolism capable of effi- health. Visceral fat has unique metabolic properties
ciently storing excess dietary energy as body fat when that contribute to prediabetes states like insulin resist-
food was abundant would have provided a survival ance when deposition in this depot is excessive
advantage during later periods of shortage. In the wake (Reaven, 1988; Wellen and Hotamisligil, 2003). The
of the rapid dietary and lifestyle change in recent gen- simple idea that our bodies are famine adapted may
erations, and the comparatively slow pace of genetic help explain why we are prone to gaining weight when
change, these foraging-adapted genes would now be we eat too much, but it says little about the metabolic
“rendered detrimental by progress” (Neel, 1962), symptoms that make weight gain unhealthy.
leading to obesity and diabetes. While a useful way to The sole focus of the hypothesis on genes is also
think about obesity generally, variations on this idea outdated in light of newer evidence that biological sus-
have been proposed to help explain the high rates of ceptibility of developing these adult diseases is also
metabolic disease among populations believed to have elevated among individuals who experienced poor
experienced especially severe nutritional conditions in nutrition during early life (Barker et al., 1989; Gluck-
the past, including the diabetes-prone Pima Indians of man and Hanson, 2006). A large research literature has
the American Southwest (Knowler et al., 1982), and demonstrated that the body’s responses to early life
several groups of South Pacific Islanders who have nutrition subsequently influences that individual’s risk
among the highest rates of obesity in the world (Dowse for developing adult diseases like diabetes and CVD,
and Zimmet, 1993; McGarvey, 1994). a process described as nutritional “programming”
The thrifty gene hypothesis was one of the first uses (Lucas, 1991) or “induction” (Bateson, 2001). For
of evolutionary reasoning to shed light on a human instance, CVD and the rate of CVD mortality in adult-
disease, and is thus a classic example of evolutionary hood are inversely related to size at birth – a measure
or “Darwinian” medicine (see Nesse and Williams, of fetal nutrition – in places like the UK, Sweden,
1994; Stearns and Koella, 2008; Trevathan et al., India, and the Philippines (Kuzawa and Adair, 2003;
518
Beyond Feast–Famine: Brain Evolution, Human Life History, and the Metabolic Syndrome 519
16
14
12
10
% body fat
8
b
nd s
an e
ne an
g
a r ig
u
l e Mo r
B eer
am t
er
ri t
t
R al
ck al
a al
Fu e a l
B F f
R ion
us
H Ra
bi
Ca Ca
m
Pi
oo
bo
p
Ca
e
la o
st
be
Se se
G um
ab
La
ts
s
ab
a
L
r
p
H
ei
ui
ph
H
E
30.1. Percentage of body fat at birth in mammals. Adapted from Kuzawa (1998).
Yajnik, 2004; Lawlor et al., 2005). Individuals who

30
were born small also experience durable changes in
biological systems that contribute to CVD, as reflected 25 Male
in their higher risk of depositing fat in the visceral Female
region, or of developing high blood pressure, impaired 20
% body fat
glucose tolerance or diabetes, or high cholesterol (Adair

15
et al., 2001; Kuzawa and Adair, 2003). When the dietary
intake of pregnant rats and sheep is restricted, their 10
offspring have much the same set of outcomes as we
see in humans born small (McMillen and Robinson, 5
2005; Fernandez-Twinn and Ozanne, 2006). This finding
suggests that the body has an ability to induce a “thrifty 0
0 12 24 36 48 60 72 84
phenotype” that is better suited to survival in nutrition-
Age (months)
ally challenging environments. It also illustrates why a
30.2. Age changes in percentage body fat in humans. Data
purely gene-based model of metabolic disease evolution
from Davies and Preece (1989), pp. 95–97.
is incomplete (Hales and Barker, 1992).
A third limitation of the thrifty genotype hypothesis
is that it merely assumes that famine was the key
source of selection on human metabolism without con- mammal studied thus far (Kuzawa, 1998). This is
sidering the actual causes of that stress and the ages at followed by a continued period of rapid fat deposition
which it is most severe (Kuzawa, 1997). There are during the early postnatal months. In well-nourished
reasons to question whether our distant foraging populations, adiposity reaches peak levels during the
ancestors experienced a major burden of famine, first year of life before gradually declining to a nadir in
which archaeological and contemporary ethnographic childhood, when humans reach their lowest level of
data suggest only emerged as an important problem body fat in the lifecycle (Figure 30.2). If the threat of
after the evolutionarily recent development of agri- famine is what drove the human tendency to build up
cultural subsistence (Cohen and Armelagos, 1984; fat reserves, it is not obvious why children’s bodies
Benyshek and Watson, 2006). Given this, famine may should do so little to prepare for these difficult periods.
have been a relatively weak force of selection on the The lower priority placed upon maintaining an energy
human gene pool (Speakman, 2006). reserve by middle childhood suggests that the back-
Additional support for this interpretation comes ground risk of starvation faced by our ancestors –
from the growth pattern of body fat in humans, shown “famine” – was small in comparison to the nutritional
in Figure 30.1. In humans, body fat makes up a larger stress experienced during the preceding developmental
percentage of weight at birth than in any other period. A prereproductive life history stage that does
520 Christopher W. Kuzawa
not prioritize energy storage is difficult to reconcile 100

with the assumption that famine was the major nutri-
tional challenge faced by human populations. 80
% RMR to brain
In this chapter, I review the causes, consequences,
and adaptive solutions to the nutritional stress of 60
infancy and childhood in hopes of shedding light on
the evolution of human metabolism. Viewing human 40
nutritional stress through a developmental lens helps
identify ages when human metabolism has likely been 20
under strongest selection. I will show how two traits
that are central to the adverse health consequences 0
0 5 10 15 20
of obesity in overnourished adults – visceral fat and
Age (years)
insulin resistance – likely evolved as components of
30.3. Percentage of resting metabolic rate (RMR) devoted to
an energy backup system that reprioritizes the alloca- the brain by age in humans. Data adapted from Holliday (1986).
tion of prized energy and glucose during a crisis, thus
allowing the body to shunt resources from nonessen-
tial functions to critical organs like the brain (for dis- which requires a constant redistribution of ions across
cussion of the function of insulin resistance during the cell membrane using energy-dependent ion pumps.
pregnancy, see Haig, 1993). Demands placed on this Humans are exceptional in the quantity of this costly
system are greater during infancy and early childhood tissue that they must sustain, and it has been estimated
than at any other age of the lifecycle, suggesting that that greater than 80% of the body’s metabolism is
some of the evolutionary seeds of adult metabolic dis- devoted to the brain in the newborn (Figure 30.3).
ease may trace to selection pressures operative during It is a notable feature of human metabolism that
early life. In addition, evidence for developmental total metabolic rate measured in adulthood (for
plasticity in this backup system and the adult diseases instance, calories expended per day) is not increased
that it contributes to suggests that its priorities may be above other mammals of similar body size despite
adjusted in response to nutritional and other stressors our highly encephalized state (Armstrong, 1983).
experienced early in the life cycle. A developmental Thus, brain expansion must have been matched by a
approach to the evolution of human metabolic disease reduction in other energetically expensive tissues
underscores the importance of the body’s internal (Armstrong, 1983). Human evolution was marked by
strategies of allocating finite resources – in addition a movement to more energy-dense and easy to digest
to the external stress of famine – as key to understand- foods (Leonard and Roberton, 1992, 1994), which may
ing the contemporary epidemic of metabolic disease. have allowed a reduction in the size and energy
requirements of the metabolically costly gut (Aiello
and Wheeler, 1995). This reduction in gut expenditure
A DEVELOPMENTAL PERSPECTIVE ON may have helped offset our increased brain needs in
ENERGY STRESS IN HUMAN EVOLUTION: adult life (Aiello and Wheeler, 1995), but this seems
THE DEVELOPMENTAL BOTTLENECK less likely during infancy and childhood. The size of
the brain relative to the body is far larger in the human
Humans have been described as naturally obese (Pond, neonate and infant than in the adult, and as a result,
1997), a characterization which is particularly fitting at the body’s total energy requirements are likely elevated
birth as human newborns are born with more body fat at this age relative to other similarly sized mammalian
than any other species (Kuzawa, 1998). Attempts to and primate newborns (Foley and Lee, 1991). More-
explain our unusual “baby fat” have traditionally over, unlike energy expended on other tissues or
looked to our hairlessness for clues, and it is widely systems, brain metabolism may not be reduced to con-
assumed that natural selection compensated for our serve energy during a period of shortage, but instead
loss of fur with a layer of insulative body fat (e.g., must be maintained within narrow limits to avoid per-
Hardy, 1960; Morris, 1967). A competing perspective manent damage (Owen et al., 1967). Thus, our large
notes that this excess adipose tissue is well-suited to brains impose a double burden on metabolism during
serve as a backup energy supply for another distinctive infancy: they increase demand for energy while
human trait: our large brains (Kuzawa, 1998). Brains restricting flexibility in metabolic expenditure when
have among the highest metabolic rates of any tissue or nutritional supply is disrupted.
organ in the body, and they are quickly damaged in the Other factors that are commonly experienced
event of even temporary disruption in energy supply. during infancy can impede the supply of nutrients,
Neuronal tissues are costly because they must be main- ensuring that negative energy balance is a regular
tained in a state far from thermodynamic equilibrium, occurrence at this age in most populations. We are
born with a naı̈ve adaptive immune system, and must infections and periods of negative energy balance
therefore come into contact with (and be infected by) decline to a small fraction of their high prevalence
specific pathogens to acquire the repertoire of anti- during the postweaning period. Because older children
bodies necessary to protect us from future infection. are far less likely to have to rely upon energy reserves
Initially, newborns enjoy immune protection from for survival, it is easy to see why the human body
several maternal sources. The first is in the form of places lower priority on maintaining sizeable body fat
maternal immunoglobulin G (IgG) antibodies acquired stores by this age.
across the placenta. In addition, exclusively breast-fed Thus, the unique energetic stressors of early life
infants are shielded from exposure to pathogens, and have left an imprint on the developmental pattern of
also enjoy passive immune protection from maternal fat deposition in humans, represented by intensive
secretory antibodies (sIgA) in breast milk. As a result, investment in the tissue in the run-up to the stresses
newborns are often quite healthy in the early postnatal of weaning, and a gradual decline in the priority given
months. However, both sources of passive immune to maintaining this reserve at older and more resilient
protection eventually wane. As energy requirements ages. But this merely shows that the body is prioritiz-
outstrip the supply capacity of breast milk by roughly ing the allocation of energy to an energetic buffer. This
6 months of age, less sterile complementary foods must energy backup must have also been accompanied by
be introduced, and infectious disease becomes the evolution of an efficient distribution and delivery
unavoidable in all but the most sanitary environments. system. Because the brain accounts for 50–80% of the
These childhood infections, in turn, are a source of body’s energy usage during the first few years of life,
nutritional stress, and indeed, it is primarily through we should expect that this delivery system – human
their effects on nutritional status that they comprom- metabolism – will be organized around the goal of
ise health and contribute to mortality during infancy ensuring a constant supply of energy to this fragile
and childhood (see Scrimshaw, 1989, for review). Once and costly organ. The availability of dietary nutrients
sick, a child loses appetite and this may be com- is variable and often unpredictable, and as we will see
pounded in some cultures by the withholding of food next, human metabolism manages this risk by rapidly
by caretakers (Scrimshaw, 1989). The common diar- modifying energy allocation in response to changes in
rheal diseases reduce nutrient absorption and diges- intake and expenditure. Multiple cues signaling nutri-
tion, while the fevers associated with many viral tional stress induce a similar response that achieves a
infections can increase metabolic rate and thus energy common end: stored fats are mobilized for use, while
expenditure. The specific symptoms may vary by ill- glucose is spared for the brain at the expense of less
ness, but the pattern of nutritional depletion that critical functions like muscle.
accompanies infections has the effect of suppressing
immune function, leaving the infant more prone to
future infection and a compounding cycle of nutri- TISSUE-SPECIFIC INSULIN RESISTANCE
tional stress (Pelletier et al., 1995). AS A LIFE HISTORY STRATEGY
The human infant thus faces a profound energetic
dilemma: at precisely the age when they are most Although long-term changes in fat stores are moni-
dependent upon provisioning by caretakers to main- tored by the brain through the effects of fat-derived
tain the high and obligatory energy needs of their large hormones like leptin, short-term changes in energy
brains, they are likely to be cut off from that supply metabolism are regulated in a more distributed fashion
chain as a result of illness and the nutritional stresses by organs like the pancreas, and also by the tissues
of weaning. It is this confluence of factors, and the themselves, which alter their own uptake and use of
synergy between nutritional stress and compromised glucose in response to changes in circulating hormones
immunity, that accounts for much of the high infant and the supply of nutrients. A sudden glut of glucose or
mortality in many societies (Pelletier et al., 1995). other substrate in the blood stream is sensed by the beta
Natural selection likely favored neonatal adiposity as cells of the pancreas, which secrete insulin into the
a strategy to prepare for these difficult periods. It is circulation. Insulin stimulates glucose uptake by tissues
easy to imagine how infants with a genetic predispos- throughout the body, initiating a negative feedback pro-
ition to deposit copious quantities of energy as fat prior cess that helps re-establish normal basal glucose con-
to weaning would be better represented among the centrations. The tissues that are not responsive to
subset who survive to adulthood to reproduce and pass insulin are few, but prominently include the organ most
on their genes (Kuzawa, 1998). vulnerable to energy shortage – the brain (Seaquist
It is important to note that these sources of energy et al., 2001). While this may at first seem paradoxical,
stress have largely receded by mid childhood: children this tissue-specific pattern of insulin sensitivity provides
have already acquired antibodies against the major the body with the ability to modify partitioning of glu-
pathogens that they are likely to confront. As a result, cose between the brain and other tissues by increasing
30.4. How body fat and insulin resistance protect the

brain. During a crisis, stored triglycerides are broken
down into free fatty acids (FFA) and glycerol. Glycerol
enters the liver as a gluconeogenic substrate, thus
Infection, increasing the pool of available glucose. Free fatty acids
Starvation, Inflammatory enter the liver where they are converted to ketone
Energy stress cytokines (+) bodies, which the brain uses as a substitute energy
ketones substrate. Free fatty acids also induce insulin resistance
(+) in the liver and muscle, which spares glucose for the
Lipolysis brain. When the nutritional stress is caused by infection,
inflammatory cytokines reach the liver and also spare
FFA Liver glucose by inducing insulin resistance in liver and muscle.
Body fat
glycerol GLUCOSE
visceral fat FFA

(–)
insulin resistance
Muscle
or decreasing insulin-mediated glucose uptake in eventually deplete – its production of insulin in type II
the periphery (e.g. muscle, liver, body fat). diabetes (formally noninsulin dependent diabetes, or
How this system of resource partitioning works is adult-onset diabetes). However, adopting instead the
well illustrated by cases of accidental insulin overdose. perspective of a young organism managing a finite
When insulin-dependent diabetics inject themselves energy supply, insulin resistance in a tissue-like skeletal
with too much insulin, this can be fatal, because it muscle allows the body to shift its priorities of glucose
“overfeeds” the insulin-sensitive periphery, leaving allocation – away from peripheral tissues and toward
nothing to fuel the insulin-independent brain (Waring the fragile and energy demanding brain (Figure 30.4).
and Alexander, 2004). Reducing insulin-mediated
uptake in the periphery has the opposite effect, as it
reduces glucose use in tissues like muscle, leaving HOW VISCERAL FAT AND INSULIN
more to be delivered to the brain. The body has two RESISTANCE HELP PROTECT THE
means of decreasing peripheral glucose use to spare BRAIN DURING A CRISIS
the brain when confronted with nutritional stress. The
first is to reduce insulin production, which reduces Given these design features, it is not surprising that
glucose uptake in the periphery. Secondly, the body insulin resistance is triggered during states associated
can influence where glucose is used with greater preci- with negative energy balance, such as starvation, infec-
sion by increasing or decreasing insulin sensitivity on a tion, or trauma (Jensen et al., 1987; Childs et al., 1990).
tissue-by-tissue basis. Skeletal muscle is a key player in During a fast, free fatty acids (FFA) are first mobilized
this flexible system. Because it is the largest consumer from the metabolically active visceral adipose depot,
of glucose, the body’s response to changes in energy which is secreted into the portal circulation that drains
status prominently involves modulating muscle glucose into the liver. Fat mobilization from this depot is
uptake by changing insulin sensitivity in this tissue. The achieved by innervation of the tissue by sympathetic
brain is an important arbiter of this response. The brain nerve fibers and, unlike other fat depots, these effects
may not be insulin sensitive, but it does express insulin are relatively insensitive to the anti-fat mobilizing
receptors and can also sense the adequacy of the supply effects of insulin (van Harmelen et al., 2002; Hucking
of glucose that it receives. In the event that cerebral et al., 2003). The liver interprets the sudden appear-
glucose flux is attenuated, the brain helps ensure its ance of FFA in the portal circulation as a signal that the
own glucose supply by inducing peripheral insulin body is being forced to mobilize fat from this depot,
resistance via effects on the sympathetic nervous and reprioritizes metabolism to protect the supply of
system and other pathways. In addition to these direct glucose to the brain. This is achieved by increasing
effects of the brain, some of the change in glucose hepatic glucose production while also inducing insulin
partitioning is co-ordinated directly by the affected resistance in the liver and in skeletal muscle, thus
peripheral tissues, as discussed in greater detail below. reducing glucose uptake (Kabir et al., 2005). In add-
From the perspective of adult metabolic disease, ition, FFA in the circulation are taken up to be used as
this reduced insulin-stimulated uptake of glucose by energy by tissues like muscle, which directly induces
skeletal muscle forces the body to increase – and insulin resistance (Roden et al., 1996).
Similar changes in how the body uses glucose are tissue, which saves the more easily metabolized and
seen in response to the stress of infection or trauma. desirable energy substrate of glucose for use by the
The body’s first response to an infection includes brain. As peripheral insulin resistance helps the body
inflammation, which helps mobilize immune and non- control where glucose is used, it seems likely that these
immune resources as a first line of defense against general features of human metabolism were forged in
tissue invasion and injury (Fernandez-Real and Ricart, the evolutionary crucible of early life nutritional stress.
1999, 2003). Inflammation is initiated in the liver in As emphasized above, the challenge of fueling the
response to signals indicating tissue injury, such as the brain, and thus the need to reduce insulin-mediated
appearance of proteins that signal the presence of bac- uptake in the periphery during undernutrition or infec-
teria, or by molecules called cytokines produced by tion, is most acute, common, and life-threatening at
immune cells like macrophages. Interestingly, in obese this age. The need to buffer brain glucose must place
individuals visceral adipose tissue is an important an important constraint on any response to nutritional
source of these cytokines, which, like FFA, are secreted stress during fetal life, infancy, and early childhood,
from fat cells into the portal circulation where they when the brain demands the equivalent of 50% or more of
induce a similar constellation of changes in energy the body’s total available energy (e.g. Childs et al., 1990).
metabolism as they reach the liver (Tsigos et al.,
1999). Why these overfilled fat cells secrete proinflam-
matory cytokines is currently a focus of intensive HOW PRENATAL NUTRITION HELPS FINE
research, and there are interesting leads. One is that TUNE THE SETTINGS OF THE BODY’S
adipocytes and the immune cells that secrete inflam- ENERGY BACKUP SYSTEM
matory cytokines (macrophages) are closely related
cells that share similar patterns of gene expression As previously alluded to, there is now a great deal of
(Wellen and Hotamisligil, 2003). It is also of interest evidence that individuals born small have higher risk of
that fat cells secrete some cytokines as they swell in developing conditions like diabetes and CVD. The pre-
size, perhaps helping the cell avoid overfilling or rup- sent discussion provides an opportunity to speculate
turing (McCarty, 1999). Regardless of the mechanism on the function of these biological changes, for they
underlying the inflammatory effects of excessive body prominently involve resetting how the body prioritizes
fat, it seems very likely that these cells are now sending traits like visceral adiposity and insulin resistance
signals that, in the past, would have been reliable indi- (for a review see Kuzawa et al., 2007). Although most
cators of infection or trauma rather than obesity. It is human research in this field has documented relation-
ironic to think that the metabolism of the overfed ships between early life nutrition and metabolic dis-
individual today, whose swollen fat cells produce high ease risk factors in later childhood, adolescence, or
levels of cytokines, may be tricked by their obesity into adulthood, a handful of studies have now investigated
sensing an inflammatory challenge or threat, inappro- these same outcomes in infants and young children –
priately initiating the same constellation of metabolic the age when the allocation of scarce glucose may be
adjustments designed to cope with starvation or most critical for survival, and thus, when these meta-
infection. bolic pathways may have been under particularly
What is clear is that multiple signals of nutritional strong evolutionary pressure. What these studies find
stress or trauma – whether FFA or cytokines – help link is that, compared to their age mates who were better-
the highly labile fat depot of the abdomen with nourished prior to birth, individuals born small tend to
metabolic adjustments co-ordinated by the liver put on more visceral fat and become more insulin
(Figure 30.4). Not unlike the effects of FFA in the portal resistant as they gain weight (Soto et al., 2003; Ibanez
circulation, these cytokines induce a state of peripheral et al., 2006). Metabolic changes in glucose use and
insulin resistance, while also mobilizing FFA stored in visceral fat are already detectable in the first year of
visceral fat for use as energy. These FFA also bathe the life, showing that a body with a prior history of
liver, and thus further contribute to insulin resistance prenatal nutritional stress is not only prone to adult
through the pathways described above (Pickup and disease, but also handles its energy and substrate
Crook, 1998; Orban et al., 1999). differently during late infancy and early childhood.
The evolutionary perspective adopted here, empha- Why the body adopts this strategy when prenatal
sizing the importance of the brain metabolism and the nutrition is scarce is uncertain, but two possibilities
pattern and sources of nutritional stress, helps clarify seem plausible. Firstly, glucose-sparing adjustments
the logic underlying metabolic adjustments that lie at could be important for protecting the brain during
the heart of the metabolic syndrome: when the body is prenatal life when intrauterine nutrition is comprom-
confronted with a challenge to energy balance, such as ised (Hales and Barker, 1992). The challenge of pro-
starvation or infection, the less critical, peripheral tecting the brain, as outlined above, does not begin at
tissues shift to using fats mobilized from adipose birth, and nutritional shortfall in utero can result when
fetal demand for energy outstrips maternal supply stress, thereby increasing survival and thus genetic
across the placenta (Harding, 2001). By this reasoning, fitness. Because the nutritional stress of weaning
then, an adjustment made in utero to boost immediate occurs prior to reproductive maturity, it represents a
survival may have unintended side-effects after birth “developmental bottleneck” through which any meta-
(Hales and Barker, 1992). bolic genes must first pass before being passed on to
The second and not mutually exclusive possibility offspring (Kuzawa, 1998). This selection would help
is that some of the adjustments have been shaped for ensure that traits that increase early life survival would
benefits accrued after birth (Gluckman et al., 2005). To stabilize into the pattern of human ontogeny across
the extent that poor prenatal nutrition or maternal many generations of differential survival. I have argued
stress are correlated with the world that the fetus will that body fat, especially the rapidly mobilized visceral
be born into, these signals could allow it to modify the fat depot, and the ability to reprioritize glucose alloca-
priorities of energy use, including the settings of this tion by inducing insulin resistance, may be two
backup system, to match the severity of postnatal examples of metabolic traits that could be beneficial
nutritional stress or challenge that it is likely to face to an infant faced with the challenge of buffering its
(for more on fetal nutrition as an anticipatory cue see most critical functions like the brain during the
Bateson, 2001; Kuzawa, 2005; Wells, 2007; Kuzawa, common nutritional stressors confronted at this age.
2008). These adjustments could help the infant manage The developmental influences on these metabolic
its precarious metabolic state and survive this traits show that the genes favored by natural selection
developmental bottleneck of early life nutritional stress do not determine the organism’s metabolic state in a
when conditions are difficult. But this shift in meta- simple one-to-one fashion. Not only does adult health
bolic priorities would also have the effect of accentu- depend upon the interaction between one’s genome
ating the metabolic derangements that accompany and lifestyle, as long appreciated, but the body also
weight gain when nutrition is chronically abundant. appears to have a capacity to adjust the settings and
When a previously undernourished body is confronted priorities of its metabolism in response to early nutri-
with excess nutrition, a strategy of prioritizing visceral tional experiences and to cues conveyed by the mother
fat deposition and sparing glucose becomes a liability, across the placenta. These biological responses may be
increasing risk of developing the metabolic syndrome, viewed as examples of the well-known importance of
diabetes, and CVD as an adult. In other words, if there developmental plasticity as a mode of human adapt-
are “thrifty genes” they code not for static properties ability (Lasker, 1969; Frisancho, 1993; also see Chap-
but for flexible strategies, or reaction norms. This abil- ter 2 of this volume). Organisms must cope with
ity to flex may help match the body’s metabolism to ecological and social change on a variety of time scales,
nutritional stress early in life, but this may plant the spanning rapid and reversible changes (e.g., breakfast
seeds for metabolic diseases caused when nutrition is followed by a fast until lunch) to much longer trends
chronically abundant later in life. that take years, decades, generations, or longer to
unfold (e.g., extended droughts, migrating to a new
ecology, an ice age) (Potts, 1998). Genes are effective
BEYOND FEAST–FAMINE: FRAGILE BRAINS at tracking the slowest, most gradual changes in ecol-
AND METABOLIC PLASTICITY ogy and diet, while homeostasis buffers rapid and
reversible changes. Developmental adjustments made
In proposing the thrifty gene hypothesis, Neel made in response to early life nutrition operate on an inter-
the elegant point that we gain insights into modern mediate time scale, allowing the organism to change its
human diseases by reconstructing the environments settings more rapidly than could be achieved by nat-
and stressors that our ancestors faced, as this provides ural selection, but in a fashion that is more durable and
a sense for what our bodies and biology are designed to stable than what the body achieves via homeostasis
expect. I have tried to show how we can approach (Kuzawa, 2005).
human metabolism from a developmental perspective In this sense, our metabolisms may not be all that
to hone this exercise in reverse-engineering. Rather different from other systems that have a capacity to
than inferring past selection from the default clinical adjust long-term settings to local conditions via devel-
perspective of adult obesity or diabetes, the develop- opmental responses, illustrated classically by the
mental approach developed in this chapter began by important effects of developmental experience on
isolating ages of high mortality to identify when systems like the brain, the immune system, and the
metabolism is most critical for survival. Identifying skeleton. Many of the body’s systems are built from a
the sources of nutritional stress at the ages of peak genetic architecture that evolved through natural selec-
nutritional mortality provides clues into the types of tion, but that – by design – rely upon information about
biological responses or strategies that would have been local ecology acquired during early development to
available to natural selection to work around this complete their construction. There is little doubt that
the size, configuration, and attachments of the body’s 4. This chapter argues that developmental adapta-
skeletal elements evolved through natural selection tions made by the fetus to nutritional stress could
operating on gene frequencies. However, because indi- contribute to a higher risk for diabetes later in life.
viduals are idiosyncratic in their behavior and thus the What are these adaptations and how might they be
mechanical loadings that they will impose on their beneficial early in life?
skeletons, natural selection constructed a system that 5. Chronic diseases often negatively impact health
has an exquisite capacity to compensate for biomecha- and survival late in the lifecycle – when one’s
nical strain, and to organize developmentally around genome has already been passed on via offspring
the pattern of use and disuse in the individual. Perhaps to the next generation. Discuss how selection pres-
it should come as no surprise that the body’s priorities sures operating early in the lifecycle might influ-
of energy allocation, which are so critical for survival, ence the evolution of diseases with late life negative
should have a similar capacity. After all, humans do impacts.
not merely vary in their culture, pathogen ecology, and 6. If we ask “What are the causes of the diabetes
pattern of physical activity, but also in their diet, nutri- epidemic?”, a public-health or medicine-inspired
tional sufficiency, and exposure to metabolically answer to this question might note that many
demanding stressors. These physiological and meta- people are eating too much and gaining weight,
bolic “loadings” may be hidden from view, but they among other factors, which leads to insulin resist-
are just as critical as components of the individual’s ance. What types of answers does an evolutionary
adaptive strategy. The ability to adjust metabolic set- approach to this problem inspire, and how are
tings to local conditions might help humans prepare they different from a public health or medical
for important adaptive challenges, like the severity of approach?
infant and early childhood nutritional stress outlined
here. However, this same flexibility may also carry
longer-term costs to health in modern environments, ACKNOWLEDGEMENTS
especially if scarcity-adapted metabolic priorities
adopted early in life are later confronted with chronic Dan Benyshek, Dan Eisenberg, Peter Ellison, Lee
overnutrition and weight gain (Gluckman et al., 2005). Getler, David Haig, Elizabeth Quinn, Melanie Vento,
It remains to be determined which of these ideas and two anonymous reviewers provided helpful com-
about the function of these traits are correct in detail. ments on various drafts of this paper.
What does seem clear is that our metabolisms are
designed to do more than survive the crisis of famine.
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31 Human Longevity and Senescence
Douglas E. Crews and James A. Stewart
INTRODUCTION biological time using physiological biomarkers, cas-

cades of interrelated metabolic events (that contrary
From a life history perspective, growth and develop- to developmental integration, lead toward disintegra-
ment are processes that enhance the functional tion), cell and transcription cycles (the fundamental
capacities of an organism through attainments of com- units of biological time), gene expression patterns,
petencies and physiological signaling across somatic changes in the proteome, epigenetic effects, and other
systems, the “growth span” (Arking, 2006). The period factors (Arking, 2006). Measures of senescence do not
following growth and development is the mature state. depend upon the passage of absolute time. Rather they
This may usefully be described as the “health span” are secondary to current competencies, organism-wide
during which the soma is most able to maintain itself, integration via messenger molecules, and the ability of
while also reproducing and investing in reproductive receptors to receive various signals and modulate cel-
effort. Senescence follows the health span. It is a lular functions (Finch and Rose, 1995). Here we exam-
later occurring age-independent, event-driven process ine human senescence within the context of overall
measured in biological time as cascades of physical organismic, large-bodied mammalian, and primate
and chemical events that increase risks of death in evolution, and humankind’s unique biocultural adap-
the next time interval, the “senescent span” (Crews, tations. Biocultural interactions extensively altered
2003; Arking, 2006). how today’s humans and earlier hominins interacted
Senescence is a biological process that only the with their environments by modifying multiple eco-
living experience; it is the final period of life history logical relationships. We start with a brief background
(LH)1 for most organisms whether unicellular or pos- on the development of evolutionary theories of life
sessing both a soma and a germline. span and how human longevity intrigued early evolu-
Senescent changes tend to be cumulative (increas- tionary thinkers and continues to intrigue modern
ing vulnerability to challenge over time), progressive biologists. Following sections explore general evolu-
(losses are gradual), intrinsic (not resulting from modi- tionary theories, the biology of senescence across
fiable environmental factors), and deleterious (reduced organisms, some senescent mechanisms, aspects of
function increases mortality risk in the next time inter- comparative biology, and briefly review similarities
val) (Arking, 2006). Senescence may be measured in in primate LH, before reviewing trends in later Homo
and human LH and life span, biocultural evolution
1
Life history (LH): In its simplest form, LH has been defined in constructed environments, and our species’ path to
simply as things to which r, the rate of population growth, is modern life styles and longevity.
most sensitive (Stearns, 1992, p. 32). It includes all aspects of a
species growth, reproduction, and survivorship. Individual and
population traits, including length of gestation, litter/clutch
size, maturity at birth/hatching, ages at first menses (menar-
che), first reproduction, weaning, last reproduction, and meno- EVOLUTIONARY MODELS
pause, birth-spacing, interbirth intervals, age at puberty, length
of growth and development period, age-specific fecundity/fertil- Historical evolutionists
ity, and age at death are the data for studying LH evolution and
examined as LH covariates. Understanding the coevolution of Darwin (Charles Robert, 1809–1882) noted that senes-
these traits, along with age-specific mortality, survivorship, and cence presents multiple problems for evolutionary
reproduction is the goal of LH research. Major components of theory (Darwin, 1859). However, it was in papers
LH research includes understanding trade-offs between somatic
maintenance and reproductive efforts, variable selective pres- presented between 1881 and 1889 that Weismann
sures on LH traits, and biocultural and behavioral influences on (Friedrich Leopold August, 1834–1914) first proposed
human LH. Life history theory is the study of the evolution and an integrated evolutionary theory of senescence and
function of life states and behaviors related to these stages
(Stearns, 1992). longevity. Weismann (1881–1889) suggested that death
528
Human Longevity and Senescence 529
was adaptive in environments with limited resources reproductive potential (MRP3: see Crews, 2003, 2007;
even if organisms began with intrinsically long life Larke and Crews, 2006) and ages when the majority of
spans of indeterminate length. In such a setting, nat- reproductive effort occurs, alleles with deleterious
ural selection (NS) would favor organisms that passed effects at older ages, but with little or no effects at
on their germlines before others and before environ- younger ones, may remain in the gene pool (Williams,
mental insults and trauma could kill them, while 1957; Kirkwood, 2002). Alleles with late-acting detri-
investing less in their somas than longer-lived, slow mental effects may then accumulate beyond ages at
reproducing individuals. According to Weismann, which NS is capable of eliminating them. Conse-
those with bodies better able to procure scarce quently, broad senescent changes may result from
resources for investing in reproduction early in life these deleterious effects at ages when reproductive
would create an array of living organisms whose life potential declines toward zero. Some may doubt that
spans were inversely proportional to their rates of such late-acting mutations are responsible for popula-
maturation and their prereproductive and reproductive- tion-level senescent processes. However, as pointed out
age mortality rates. He saw that the quicker a species by Lasker and Crews (1996), variable mutations and
achieved LH landmarks, the shorter its average and mutation rates across populations and environments,
maximum life spans need be. coupled with linkage disequilibrium, will lead to differ-
Many extant species show a semelparous LH, death ent alleles accumulating in various populations. As
occurs after a single lifetime reproductive event. This is long as these are not linked to other alleles that reduce,
particularly so for insects, annual plants, and some fish or they reduce fitness themselves, gene flow will spread
species (salmon). Unless an organism must contribute these alleles and, importantly, their linked haplotypes,
to raising its young, there is little push for somatic across a species. [For example multiple viral DNA seg-
maintenance after reproduction (Weismann, 1881– ments have hitchhiked within the human genome for
1889; Crews, 2003, 2005a, 2007; Larke and Crews, millions of years, up to 8% of the total (Feschotte
2006). As larger organisms commonly develop more 2010).] When linked haplotypes show benefits to repro-
complex somas, provide parental investment2 (PI) to ductive success (RS) in many environments, NS may
their offspring, who develop slowly, and have more maintain or increase their frequency in local settings.
than a single reproductive cycle (iteroparous), their Population bottlenecks, founder effects, and various
deaths are postponed to later ages by NS. Weismann forms of genetic drift also may increase frequencies
suggested that for most organisms, there is no advan- of late-acting detrimental alleles within local popula-
tage to keeping ancient, less competitive individuals tions. Thus late-acting detrimental alleles may “hitch-
around to deplete resources needed for younger gene- hike” along with beneficial alleles within linked
rations. As with many of Weismann’s conjectures, haplotypes, hidden till life spans increase to ages at
such group-selection models are not accepted today. which they are expressed.
However, he did presage Dawkin’s (1989) selfish genes In addition to addressing mutation accumulation
and Wilson’s (1975) group selection approaches following Medawar (1952), Williams (1957) recognized
and conceptualized a disposable soma, as was later that pleiotropy also might lead to senescence. Alleles
developed more fully by Kirkwood (1977). Additionally, beneficial during the growth span or that enhance
many later theoretical perspectives on senescence, reproduction and MRP during the health span may be
including those of P. Medawar (1952), G. C. Williams incompatible with long life. Alleles enhancing senes-
(1957), T. B. L. Kirkwood (1977), R. Holliday (1997), and cence in mid- to late-life, but improving survival during
W. D. Hamilton (1966), were presaged by Weismann’s infancy, childhood, and attainment of MRP exhibit
(1881–1889) insights into evolutionary processes and antagonistic pleiotropy (early benefits with late-acting
senescence. deleterious effects). Due to trade-offs between repro-
duction and somatic maintenance, once an organism
begins reproducing and fledging offspring, NS
Modern evolutionists
gradually loses its ability to eliminate alleles that are
Age-specific gene action and pleiotropy deleterious to the organism’s extended somatic main-
Medawar (1952) first suggested age-specific gene tenance. For example, apoptosis is crucial during
action and mutation accumulation contributed to sen- embryonic development for sculpting the developing
escence. As NS diminishes at ages beyond maximum organism as stem cells create more new cells than are
3
Maximum reproductive potential (MRP): Is the point in life at
2
Parental investment (PI): All expenditures of parents’ time, which an organism is sufficiently mature to not only bear/sire
energy, and future reproductive effort on one offspring at a cost offspring, but also best able to rear and fledge any offspring
to parents’ abilities to invest in their own somas or other pos- produced with maximum efficiency (Crews and Gerber, 1994;
sible offspring and enhance their own fitness (Hamilton, 1964, Gerber and Crews, 1999; Harper and Crews, 2000; Crews, 2003;
1966). Larke and Crews, 2006).
530 Douglas E. Crews and James A. Stewart
needed. While the soma is sculpted, external markers are minimized. However, once sexual maturation and
(ligands) regulate apoptosis of excess cells. Once adult- MRP are attained, a trade-off or competition between
hood is achieved, animals are no longer growing or investing in maintaining the “disposable soma” or
developing and rates of apoptosis are adjusted accord- reproducing the “immortal germline” through off-
ingly as morphogenesis is completed. During adult- spring ensues (Kirkwood, 1990, 2002, 2005). Models
hood most cells that are damaged, malfunctioning or proposing LH trade-offs between the soma and repro-
show damaged DNA are marked for apoptosis by ductive effort mainly focus upon the postgrowth span
internal cues (e.g., mitochondrial factors, p53). How- of LH. The soma is not disposable prior to achieving
ever, proliferation of new cells to replace those that are reproductive maturation and RS. Trade-offs expressed
worn out and/or lost through apoptosis may not be during the growth phase are associated with early LH
balanced and tissue deterioration may occur. Loss of strategies of high versus low early life reproduction
cells from apoptosis and accumulation of senescent and rapid versus slow growth and development. In
cells may jointly contribute to senescence and tissue some species LH patterns have deep evolutionary roots
deterioration (Campisi, 2003). Williams (1957) also reflecting phylogenetic inertia. For example, mayflies,
suggested that as life span increases NS bumps up fruit flies, annual plants, many insects, amphibians,
against detrimental alleles that have been retained and fish show rapid life histories, little to no PI, rapid
through mutation accumulation, at what was previ- growth, and high numbers of eggs, seeds, and sperm
ously the upper limit of reproductive effort. When this upon reproductive effort; along with rapid senescence
occurs, alleles at other loci that modify the late-acting and high intrinsic mortality. Conversely, other species
detrimental effects of accumulated alleles, or alternate of insects, plants, amphibians, reptiles, fish, and
alleles at the same loci, may increase in frequency if mammals, notably cicadas, wasps and other hymenop-
they promote longer life along with greater RS. How- tera species, redwood and bristlecone pine trees,
ever, any alleles that improve prereproductive survival turtles, sharks, whales, and elephants show a different
or improve RS in early life will not be eliminated via LH pattern. There are no phylogenetic continuums
NS, regardless of their late life effects. of LH strategies nor does phylogeny necessarily predict
LH, different species within even a single genus may
Disposable somas and immortal genomes show different LH patterns and the same species may
Accumulated evidence now suggests that senescence show markedly different LH patterns under different
may occur in most organisms. For many decades fissile environmental constraints.
organisms were thought to not show senescence and Early in life and during the period of maximum
therefore be in a sense immortal. However, recent reproductive effort, NS favors somatic maintenance
research on Escherichia coli and fissile single celled in species that reproduce multiple times (iteroparous)
prokaryotes suggest they do senesce (Stewart et al., or that show PI in their offspring after birth/hatching
2005). Not only do eukaryotic, sexually reproducing (Hamilton, 1964, 1966; Crews, 2003, 2005a, 2008;
species with telomeres to shorten with each round of Larke and Crews, 2006). As life continues, investment
mitosis, LH stages to grow and develop through, antag- in reproductive effort eventually takes priority over
onistic pleiotropy, vital macromolecules to oxidize, somatic maintenance and senescent processes may
and proteomes that are degraded over time show sen- not be eliminated, because additional somatic invest-
escence, it now seems that all living organisms may ments yield trivial reproductive benefits. Eventually,
show senescence. the net effect of NS declines to zero. Metazoans have
Kirkwood’s (1977, 1990, 2002, 2005) and Kirkwood complex, interrelated and interdependent cells, organs,
and Holliday’s (1979) elaborations of Weismann’s dis- and systems within their somas. Senescence of cells
posable soma theory of senescence proposes a distinc- begins early in the life span as strategic resources are
tion between evolutionary theories and physiological directed toward replicating the immortal germline at
descriptions of somatic senescence (see also Crews, the expense of the soma (Austad, 2005a; Kirkwood,
2003). An organism’s resources, such as energy, are 1977; Hayflick, 1979). Among species with high PI
limited and must be divided between self-preservation and multiple reproductive cycles, NS works to main-
(the soma) and continuance of the immortal germline tain the parental soma because it is the sole reproduct-
across generations (reproduction). During the growth ive organ and source of continued investment in
span resources are invested into the soma. Throughout reproductive effort and PI. Simple mathematical for-
the growth span, the soma and germline share the mulas, such as the Gompertz or Weibull equations,
same goal, producing a mature soma to pass on the model the increase in somatic susceptibility over time
germline. Because the soma is the organ by which the from multiple, interrelated, and unrelated intrinsic and
immortal germline ultimately must reproduce itself, extrinsic factors that combine to eventually kill all
over the growth span trade-offs between somatic organisms. All metazoans senesce after they attain
growth/development and transmitting the germline MRP. Although some processes of senescence even
may be initiated as early as fetal life, most occur after evolutionary theories of senescence advanced in
MRP. For some species, a previously unidentified LH parallel with molecular biology. Cellular and compara-
stage may lie just beyond the senescent phase. During tive biology, breeding experiments with animal models
this “late-life stage,” the rate of increase in senescence and, more recently, growth of cells in laboratories,
and mortality hazards may slow among some experi- analyses of DNA and transfers of DNA into and out
mental and free-living populations (Carey et al., 1992; of animal models have improved understandings of
Carnes and Olshansky, 2001; Rose et al., 2005b; Perls, cellular senescent biology. It is now clear that across
2006; Rauser et al., 2006). organisms, multiple alleles at many loci and differen-
Rauser et al. (2006) suggest that such a late-life tial processing of proteins produce complex molecular
phase may begin when an organism’s survivorship pathways modulating physiological functioning.
and fecundity deteriorations cease and mortality rate Some of these are incompatible with longevity; others
increases approach zero. The Gompertz equation are associated with high somatic maintenance and
(ðxÞ ¼ Aex ) predicts that as organisms age, their mor- extended life spans. Among humans both culture and
tality rates increase exponentially (Hamilton, 1966, environment influence and alter these multiple genetic/
reviewed in Box 13.1 in Crews and Ice, 2010). However, protein-based predispositions. Across species and
the slope of the Gompertz equation decreases slightly populations average age at first reproduction and
after about age 85, suggesting decreasing increases average life span are closely associated. Variation
in mortality may happen in late life. Late-life survival in life spans and reproductive potential within and
is better modeled by Hamilton (1966): between populations and species shows that environ-
ments modulate and extensive genetic variation
X
ry Aex
sðxÞ ¼ e lðyÞmðyÞ and ðxÞ ¼ underlies LH (Perls, 2001, 2006; Carey and Judge,
y¼xþ1
1þ ½2 Aðex 1Þ 1
2001; Perls et al., 2002; Crews, 2003; Perls and Terry,
Where s(x) is the variance in survival and (x) is the 2003; Pak et al., 2003; Bredesen, 2004; Holliday, 2004;
average age at death. Other variables in the equations Austad, 2005a, 2005b; Kirkwood et al., 2005; Rose
are, x representing age, r the Malthusian growth rate, et al., 2005a, 2005b; Christensen, et al., 2006; Harper
l(y) the specified survivorship to age x, and m(y) et al., 2006a).
age-specific fecundity, where y is the net expected
reproduction at all ages x and higher. A is an age- Cellular biology
independent parameter representing baseline mortal-
ity within the population, and a is an age-independent Cell replicative ability
parameter representing senescence (rate of aging in Hayflick (1965) reported that mitosis by dividing cells
Hamilton’s terms). Data from some laboratories and (fibroblasts) cultured in vitro was limited. Contrary to
experimental species suggest mortality rates at later the then prevailing opinion, that dividing cells pos-
ages may follow patterns represented by Hamilton’s sessed an unlimited capacity for self-reproduction,
(1966) equations. This leads to suggestions that a late- Hayflick observed that fibroblasts from newborns
life phase with nonincreasing mortality rates may doubled in vitro only about 50–60 times. How, and if,
occur late in the LH of some multicellular organisms Hayflick’s eponymous limit is associated with human
(Hamiliton, 1964, 1966; Rose et al., 2005b; Rauser senescence was then, and remains today, largely
et al., 2006). Hamilton (1966) suggested such a unknown. Some researchers suggest that dividing cells
phenomenon might reflect declining NS over time. may come close to their in vitro doubling limit when
Humans may show some late-life stabilization of age- they produce and maintain a mature adult reproduct-
specific mortality rates as age-related deterioration ive human. However, current estimates are that only
slows or ceases after 85 or 100 years (Perls, 2001; about 42 cell doublings by the zygote are needed to
Doblhammer and Kytir, 2001; Rose et al., 2005b; produce a mature infant and only another 4–6 to grow
Crimmins and Finch, 2006; Rauser et al., 2006). an adult soma and maintain it thereafter (Dennison
et al., 1997). This would leave the average person with
more than sufficient cell doublings to maintain their
THE MODERN SYNTHESIS AND soma over 10 decades. Limited cell doublings as
SENESCENT BIOLOGY defined by Hayflick (1965) may still be related to cell
culture methods. By dividing the cell population, the
The synthesis of evolutionary theory with genetics number of primary fibroblasts left to produce new cells
combined with developments in multivariate statistical is halved also (Cristofalo et al., 1998, 1999, 2003; Clark,
analyses of genes and population genetics during 1999). Among the criteria for an eponymous limit is a
the mid twentieth century allowed some analyses of specified time during which the culture must cover
the complex gene–environment interactions produ- its environment; without a time limit, cultures may
cing senescence. During the late twentieth century, continue dividing slowly to confluence.
Animals do not appear to “run out” of cells over mass (Aviv, 2002; Blasco, 2005). However, other bio-
their life spans due to limited cell proliferations in vivo, markers of senescence are not highly correlated with
nor do doublings in cell culture correlate as strongly telomere shortening (Blasco, 2005).
with age as was originally suggested (Hart and It is now clear that shortening of telomeres limits
Tuturro, 1983). For example, total doublings for cells cellular replicative life spans and leads to the Hayflick
cultured from the same individual may show an aver- limit of human fibroblasts in vitro (Olovnikov et al.,
age of about 50 doublings, but a range from 10 to 90 1996; Shay, 1997; Aviv, 2002; deLange, 2002). Dividing
doublings (Hart and Tuturro, 1983). Cells from differ- cells that reach their replicative limit in vivo become
ent individuals of the same age also show wide vari- senescent and tend to accumulate in somatic tissues.
ation in their total numbers of doublings; cells from Such data suggest that chromosome shortening meas-
infants average about 50–60, but range from 25–120, ures or represents intrinsic cellular senescence, an
while those from persons aged 65 years average about internal biological clock in dividing cell clones. Still,
20 doublings, with a range from 5–50. Across individ- cell replicative capacity is not closely associated
uals of all ages the average is about 35 doublings, but with individual life spans. An unknown number of
again the range is large, from 0–120 (Hart and Tuturro, variables – including cell type, donor age, oxidative
1983). Additionally, no significant correlation of fibro- stress, and heredity – influence correlations between
blast doublings and age of cell donors, was observed in telomere shortening and age, both across and within
a small sample of healthy Baltimore Longitudinal individuals. Telomere length varies across peripheral
Study of Aging participants (n ¼ 42) (Cristofalo et al., lymphocytes from the same individuals, between simi-
1998, 1999). Also problematic is the finding that fibro- lar cells from different individuals of the same age, and
blasts from some very old individuals show no across cell cultures of fibroblasts from the same donor
doubling potential at all, yet these individuals continue (Harley et al., 1990; Hastie et al., 1990; Slagboom et al.,
to survive. Given these accumulated data, relationships 1994). Studies of human peripheral lymphocytes sug-
between in vitro doublings and in vivo senescence gest an average loss of telomeric DNA of about 31–33
are unclear and may be less important than other base pairs (bp)/year (Hastie et al., 1990; Slagboon et al.,
processes (Cristofalo et al., 2003). 1994). The average, across various types of human
During terminal passages in vitro cells do tend to cells, ranges from 40 to 200 bp/division (Allsopp,
show multiple alterations that are similar to those of 1996), compared with an average of 50 bp/doubling in
senescent cells in vivo (Clark, 1999; Campisi, 2003; cultured cells. Telomere length is sexually dimorphic
Aviv, 2002). Data on telomere shortening suggest that in humans at birth, women’s telomeres are longer then
in vivo skin, thyroid, immune, and digestive cells may men’s (Aviv, 2002). Men also appear to senesce faster
fail to replace themselves adequately with increasing than women until late life (Foley, 1986; Perls, 1995;
age (Clark, 1999). In general, loss of proliferate cap- Anderson-Ranberg et al., 1999), although this may
acity in vitro is not thought to produce or reflect pro- not be so (Graves et al., 2006). Men may require more
cesses of senescence. Loss of replicative capacity shows cell doublings to accommodate their 15–20% larger
how a complex molecular system fails to maintain body sizes, exhausting their shorter telomeres earlier
itself infinitely due to intrinsic fragility and random in life. Although attrition of telomeric DNA tandem
losses of function. Average numbers of doublings in repeats (TTAGGG) paces in vitro replicative history of
vitro are correlated loosely with age of cell donors but primate, including human, cells, a similar association
are not highly predictive of individual life spans. Loss is not observed in rodent cells (Aviv, 2002). Available
of replicative capacity does not appear to underlie sen- evidence does not suggest a causal relationship
escence in humans or mammals. However, senescent between telomere attrition and biological senescence
cells with traits similar to those of cells experiencing in humans (Aviv, 2002). One cause, oxidative stress, is
replicative senescence do accumulate with time in a promoter of cellular senescence, thus telomere length
human organs. also may indicate exposures to reactive oxygen species.
Telomeres Apoptosis
Cells of patients with syndromes mimicking some Senescence occurs at the molecular level (Arking,
aspects of somatic senescence, e.g., ataxia telangiecta- 2006), but is expressed as somatic aging, cellular dys-
sia, Werner’s syndrome, Bloom’s syndrome, trisomy function and death (Campisi, 2003). Senescent cells
21, dyskeratosis congetialia, aplastic anemia (Blasco, accumulate in most tissues with increasing age. This
2005), show progressive telomere shortening. Telo- may partly reflect sluggish apoptosis (programmed cell
mere shortening also associates with heart failure, death). Tissues composed of dividing and nondividing
immunosenecence, digestive tract atrophies, infertility, cells both accumulate senescent cells with age:
reduced viability of stem cells, reduced angiogenic the former partly due to the Hayflick limit and loss
potential, reduced wound-healing, and loss of body of telomeric DNA, the latter secondary to intrinsic
molecular stress, wear-and-tear, oxidative stress, and composed of short-lived, litter-baring, low PI species,
other processes. Apoptosis is associated with the they do not show a similar proportional timing or pat-
appearance of distinctive molecular markers. Among tern of LH to even the smallest of primates. Multiple LH
most sexually reproducing organisms the force of NS features observed among insects and rodents are not
continually decreases over the life span after matur- found in primate and humans (e.g., dauer stages,
ation. It seems likely that over evolutionary history, litters). Such laboratory species tend to reveal basic
alleles beneficially affecting cellular processes and processes of cellular senescence. What they do not illus-
leading to greater cell stability would have evolved via trate is how senescence is expressed as aging and
NS. However, increasing cell and organ dysfunction is longevity in humans. Humankind uses biocultural and
observed with increasing age in most modern species. genetic adaptations, physiological and biological
This appears to be due to intrinsic molecular alter- systems, behaviors and constructed environments in
ations that disrupt cellular processes rather than to their responses to the age-independent, event-driven
processes at the organ level that lead to systemic organ processes of senescence that occur over biological time.
failure. In complex organisms, it seems that both apop- The same cascades of senescent physical and chemical
tosis and cellular senescence may have evolved to events likely occur in all iteroparous sexually reprodu-
suppress the transformation of functional cells to can- cing species (Arking, 2006). How evolution and pheno-
cerous cells or cells that might harm the entire organ in typic adaptability have slowed these processes and risks
other ways (e.g., autoimmunity, reduced OXPHOS, of death from altered gene expression, proteomic disin-
mutant mtDNA). Multiple alleles influence apoptosis tegration, and disruptive metabolic events is what dif-
(Bredesen, 2004) and create conditions that mimic ferentiate species-specific and population-specific LH.
many of the effects of senescence seen in humans, In general, phylogeny is poorly associated with lon-
e.g., Werner and Bloom syndromes, and other patholo- gevity (Rose, 1991). However, comparative biology has
gies associated with shortened telomeres (Blasco, produced multiple insights on human senescence, and
2005). Continued apoptosis is one method for main- likely will continue to do so (Austad, 1997, 2003; Crews,
taining the soma in response to continued cellular 2003). However, Austad (2003, p. 1327) points out that
damage and deterioration. However, inappropriate “All of the best known and most widely employed
apoptosis may limit life spans via antagonistic models for aging are short-lived taxa . . .” Although
pleiotropy and loss of nonsenescent cells. Lack of commonly studied animals provide limited informa-
apoptosis may allow senescent cells to survive and tion on how human LH, aging, and longevity are struc-
deteriorate or compromise tissue and organ function tured (Austad, 2003), they do show that high “lifelong
or become cancerous. Apoptosis may be delicately demographic heterogeneity” exists between and within
balanced to eliminate most senescent and damaged species (Vaupel, 2001; Rose et al., 2005a, 2005b). Life-
cells, but over the life span allows some to survive long demographic heterogeneity is measured by the
and damage the organism. variability in mortality/survival patterns observed
between cohorts and groups within populations; each
requires a different Gompertz equation to fit its vari-
ANIMAL MODELS AND able LH experiences (Carnes and Olshansky, 2001).
COMPARATIVE BIOLOGY Experimental data from insects, rodents, and humans
indicate broad LH variation within populations large
Humans are complex organisms. They show several and small, and, by extension, different cohorts within
LH attributes that seem to differ significantly from populations (Dobelhanner, 2000; Stearns et al., 2000;
those of most other organisms (Austad, 1991; Hawkes Charlesworth, 2001; Arking et al., 2002; Kirkwood,
et al., 1997, 1998; Alvarez, 2000; Smith and Bogin, 2005; Kirkwood et al., 2005; Rose et al., 2005a, 2005b;
2000; Carey and Judge, 2001; Bird and Bird, 2002; Perls, 2006). This illustrates the multiple influences of
Crews, 2003; Crews and Gerber, 2003; Howell and environments and genes on LH. They also illustrate
Pfeiffer, 2006; Larke and Crews, 2006; Christensen one pitfall of comparing demography, genes, or biology
et al., 2006). One problem when applying results from across, within, and between species. Populations
experimental animal models and molecular experi- within species inhabit a variety of local and regional
ments to humans is that, thus far, only a limited environments (Rose et al., 2005b), producing multiple
number of organisms have been studied (Austad, adaptive landscapes and variable adaptations.
1994, 1997). Yeasts, nematodes, fruit flies, and mice
are the most frequently used animal models for study-
ing longevity enhancement and senescent process. All Drosophila
are “demonstrably inept at aging successfully” (Austad, Lacking a close evolutionarily relationship, fruit flies
2003; p. 1327). As mammals, mice share many homolo- do not recapitulate age-related declines and diseases
gous gene loci with humans. However, as a clade observed among humans. However, these organisms
show commonalities in their patterns of molecular and diet, mice with wild grandsires show changes in corti-
cellular senescence, illustrating genetic and environ- costerone and testosterone that resemble those of
mental influences on diminishing cellular functions standard laboratory animals, however their mean lon-
with age (Arking et al., 2002; Grotewiel et al., 2005). gevity does not differ significantly from mice-eating
Artificial selection produces populations showing standard laboratory chow (Harper et al., 2006b).
variable longevity in multiple Drosophila species Calorie-restricted laboratory mice show higher mortal-
(Luckinbill et al., 1984; Rose 1991; Pletcher and ity during early life, lower mortality in later life, and
Curtsinger, 1998; Service, 2000; Charlesworth, 2001; have fewer cancers than ad libitum fed mice. Under-
Arking et al., 2002; Rose et al. 2005a). Selecting longstanding how CR changes physiology and longevity of
lived or late-reproducing fruit flies produces significant laboratory-bred mice may aid in understanding pro-
increases in mean and maximum life spans after a few cesses of human senescence. Laboratory selection for
generations. Given the controlled laboratory environ- either long-life or late reproduction in rodents extends
ment, allelic variation must contribute to improved lon- average and maximum longevity. As with fruit flies, a
gevity. As yet, directional artificial selection on longevity reservoir of longevity-enhancing alleles is exposed in
has not shown an upper limit to life span (Curtsinger laboratory rodents. Wild rodents show a range of LH,
et al., 1992; Arking et al., 2002). Among a single strain of body sizes, and longevities with the largest and longest-
Drosophila, a variety of stressful external stimuli may lived inhabiting isolated islands and tropical settings.
induce a variety of longevity phenotypes, suggesting Without major predators and when isolated from com-
that multiple interrelated mechanisms modulate their petition, even rodents show longer lives and larger
LH and life span (Arking et al., 2002). Combinations body sizes. This suggests that as populations develop
of longevity-enhancing alleles also may recombine, mechanisms that reduce predation or competition
predisposing latter generations to increasing life spans. for resources, isolation for rodents and culture for
These results show that simple mechanisms influence humans, longer lives and increased body sizes ensue.
longevity, and that life span is not intrinsically limited
in most species. Current environments, evolutionary Nonhuman primates
history, and multiple evolutionarily stable strategies Most primates show average life spans for their body
across populations within species may produce inertial sizes above those predicted by regression models based
barriers that limit life span. Genotypic variation for on extant mammals (Finch, 1990; Carey and Judge,
survival, initial, and age-specific mortality rates is high 2001). Based upon longevity of 587 captive mammalian
in fruit flies. However, specific DNA segments do not species, primates are not necessarily the longest-lived
correlate highly with demographic and functional for their body sizes (Austad and Fischer, 2005). Even
measures of senescence (Burger and Promislow, 2006). small- and medium-build primates tend toward longer
Responses of young flies to early life stressors may alter life spans than predicted for mammals of their size.
their homeobox genes rather than other DNA segments They also tend to have larger brains for their body sizes
(Burger and Promislow, 2006), possibly modulating pre- than do most other mammals. Primates generally birth
cursors of senescence during early life. single offspring, show high PI, arboreal adaptations,
Drosophila species illustrate the relative simplicity and live in social groups, traits reducing susceptibility
of modulating longevity in a laboratory setting (Arking to environmentally imposed mortality and predation
et al., 2002). They also reveal a reservoir of genetic (Shea, 1998; Carey and Judge, 2001; Austad and
variation for senescence-slowing alleles not expressed Fischer, 2005). Among prosimians, monkeys, and apes
in wild populations. Senescence-slowing alleles are not multiple LH strategies are observed. However, being
advantaged in wild populations because longevity long-lived and slow-reproducing mammals for their
enhancement often is associated with reduced RS. In body sizes with large brains are common traits, sug-
natural settings NS limits frequencies of “longevity- gesting that these reflect some similar evolutionary
enhancing” alleles because they reduce RS. Unlike pressures that have influenced LH.
Drosophila, humans, particularly men, may increase In general, primates progress through their LH
their RS by living longer; women also may, but not as phases and transitions more slowly then similar-sized
much as men (Marlowe, 2000; Crews, 2003, 2008). The nonprimate mammals (Austad, 1997; Shea, 1998;
reservoir of longevity-enhancing alleles seen in many Carey and Judge, 2001; Leigh, 2004; Austad and
wild-living populations already may be expressed as Fischer, 2005; Crews and Bogin, 2010). Most primates
extended longevity in humans (Crews, 2003). lie above regressions lines predicting average life
spans of mammals from average birthweight, adult
Rodentia encephalization index (ratio of brain size to body size,
Harper et al. (2006b) question the applicability of see Austad and Fischer, 2005), adult body size, or cra-
research on laboratory-bred animals to human longev- nial capacity (Finch, 1990; Carey and Judge, 2001;
ity (see also Austad, 2003). On a calorie-restricted (CR) Leigh, 2004). This is most obvious among large-bodied
apes. They may fall above such regression lines by a evolution”4 (Goodman and Leatherman, 1999; Carey
standard deviation or more. Encephalization appears and Judge, 2001; Aiello and Wells, 2002; Crews, 2003,
to characterize primates, along with extended off- 2005a, 2008; Crews and Gerber, 2003; Larke and
spring dependency, high PI, and extended longevity. Crews, 2006; Arking, 2007). Physical development in
This suite of LH characteristics has been identified as utero, physical maturity at birth, length and timing of
a possible base for the modern human LH strategy postnatal growth and development, ages at menarche,
(Shea, 1998; Bogin, 1999; Smith and Bogin, 2000; first and last reproduction, and menopause, reproduct-
Crews, 2003; Crews and Bogin, 2010). ive effort, fertility, RS, rates of senescence, and longevity
A high encephalization index is associated with continue to vary across the four remaining large-bodied
greater behavioral adaptability. This allows organ- primate species and local populations (Finch, 1990;
isms to use more self-motivated and opportunistic Carey and Judge, 2001; Crews, 2003; Leigh, 2004;
behaviors when responding to their environments. Larke and Crews, 2006). Alterations in early LH par-
Even early hominins had and modern apes show high ameters may alter all later aspects of LH, eventually
encephalization. Encephalization among Homo pro- leading to changes in late-life survival and reproductive
vided a basis for developing cultural activities leading patterns (Crews, 2003; Finch and Crimmins, 2004;
to biocultural evolution. Primates generally birth a Crimmins and Finch, 2005, 2006; Finch, 2005; Larke
single offspring. Although twining is the norm in and Crews, 2006). For example, within cohorts of
some New World monkeys (marmosets and tam- modern populations, low childhood mortality and
arins), it is rare in others (Cebids). Twinning among infectious disease morbidity tend to produce lower
humans (about 3–5% of births) is relatively common. adult mortality and correlate with extended longevity
Providing high PI to one offspring over an extended (Finch and Crimmins, 2004; Crimmins and Finch,
period of time is energetically more efficient for parents 2005, 2006; Finch, 2005). This was predicted by
than providing for two or more over a shorter period. Weismann (1881–1889) who surmised that life spans
All primates share a suite of LH traits found across are inversely proportional to rates of maturation and
long-lived species (Shea, 1998). Today humans express prereproductive mortality. These and other results sug-
a high PI evolutionarily stable strategy (ESS) (Crews, gest that models based upon retention of reserve
2003, 2008; Larke and Crews, 2006). Human infants capacity (RC) into older ages and life in cushier environ-
are among the most physically altricial of primate ments partly explain increases in later Homo and
and mammalian offspring. Even so, humans show particularly modern human longevity (Crews, 2003,
the shortest birth intervals, highest RS, and youngest 2005a; Caspari and Lee, 2004; Finch and Crimmins,
weaning ages of extant large-bodied apes. These 2004; Crimmins and Finch, 2006; Larke and Crews,
are LH traits correlated with fitness and evolutionary 2006; Bogin, 2009; Crews and Bogin, 2010). Such
success. Since the Miocene, monkey genera have results do not support models suggesting that adult or
been more successful than have apes at expanding postreproductive mortality rates influence patterns of
their ranges and competing for survival (Leigh, 2004). growth and development. Rather the opposite, mortal-
Monkeys, like humans, have shorter birth intervals, ity and infectious disease rates during the growth
younger ages at weaning, and higher RS than do extant phase potentials lower adult and late-life mortality
large-bodied apes. They also are smaller and show less and improved survival.
postweaning PI and provisioning. Among the Homini-
dae, humans show more monkey-like LH adaptations
than do other large-bodied apes.
Genes, evolution, and cell biology
Biological, observational, and laboratory research have
HUMAN LONGEVITY AND SENESCENCE advanced understandings of mechanisms by which
many species (e.g., elephants, whales, sharks, tortoises,
Foraging, scavenging, gathering, hunting, horti- humans) have extended their life spans past 50 years,
culture, and eventually agriculture altered patterns while other species have not. However, specific genetic
of LH, particularly survival, reproduction, and PI modulators and biomarkers have not shown strong
among hominins. Changing subsistence strategies associations with longevity. Genetic variability
and technologies altered energy availability and the between populations of individuals within species and
human niche. Cultural developments and niche con-
struction modified human environmental exposures 4
Biocultural evolution: The interplay of culture and biology on
(Odling-Smee et al., 2003; Armelagos et al., 2005) human evolutionary processes. The scientific study of relation-
producing differential longevity across populations ships between culture and human biology that have shaped
modern human variation and the resources available to humans
and groups (Crews, 2003, 2005a, 2008). Sociocultural across cultures. Only among humans are biocultural pressures
adaptations by humans promoted “biocultural on evolution observed.
across species in the organization of their DNA and lead to about 300 000–400 000 different protein forms
genes hinders comparisons across humans and other in humans (Jaenisch and Bird, 2003). As understand-
organisms (Arking et al., 2002; Hahn et al., 2007). For ings of cellular senescence expanded, mitochondrial
example, chimpanzees and humans show relatively (mtDNA) came under closer scrutiny. Some senescent
high population-level differences in their genetic struc- processes, e.g., loss of muscle mass (sarcopenia), are
tures (Fischer, et al., 2006). Additionally, among associated directly with mtDNA mutations. However,
humans, genetic variation is structured by cultural no single mutation is associated with a majority of
behaviors. For example, there is little Y-chromosome senescent processes (Pak et al., 2003). A number of
variation among members of the Cohen priesthood polymorphisms (e.g., mtDNA, APOE, HLA alleles/
(Hammer et al., 1997). Alleles at the BRCA 1 and 2 haplotypes, presenilins, BRCA 1 and 2 alleles) are
and the apolipoprotein (APO) E loci, along with human associated with senescent-related diseases (e.g., sarco-
leukocyte antigen (HLA) haplotypes show variable fre- penia, autoimmunity, dementias, cancer) that shorten
quencies across populations. Some genes are associ- life span. Others, such as low levels of APOC3 are
ated with early mortality, while others are found at associated with longer life spans (Atzmon et al.,
high frequencies among long-lived individuals of most 2006). A monotonic over-representation of the
populations. For example, across samples from differ- APOC3–641CC genotype is observed at older ages in
ent populations, different HLA haplotypes are associ- humans. Relatively infrequent (10%) at age 60 years,
ated with longevity. Genetic variation within and this allele is found at 25% among survivors to 100 years
across human samples limits any utility of comparing (Atzmon et al., 2006). APOC3–641CC predisposes to a
alleles associated with longevity to nonhuman pri- lipid phenotype compatible with long-life in modern
mates or other animals (Fischer et al., 2006). There settings. This association may not have occurred in
are multiple human longevity genotypes and pheno- other populations at other times during hominin
types. Local selection differentials, population size, evolution. Among some populations with low dietary
genetic/phenotypic heterogeneity, and multiple genetic fat and cholesterol intakes, such as the Yanomami and
and population processes structure correlations of LH other American Indian populations, a high frequency
characteristics with specific alleles (Rose et al., 2005b). of the APOE*4 allele, apparently with no APOE*2
Population sizes, mating patterns, migration and sex alleles prior to European contact, suggest the APOE*4
distributions influence genetic variation in all species. allele may have been advantaged because it maintains
Along with demographic, evolutionary, and environ- cholesterol levels (Crews et al., 1993). In such low
mental factors, sociocultural behaviors have struc- cholesterol settings, APOE*4 alleles might have helped
tured human genetic variability for LH. maintain cholesterol levels for generating steroid
Humans appear to show some unique and many hormones during gestation, growth, development,
similar LH traits compared to nonhuman primates and and reproductive effort. The HLA haplotypes and
other long-lived animals. Humans are not the most APOE alleles show age-related frequency differences
long-lived mammals, whales probably are. Verifying across populations. Different HLA haplotypes are asso-
that a LH trait is unique to a species requires broad ciates with late-life survival in each population exam-
comparative surveys, quantitative assessments, and ined. In modern Westernized populations, the APOE*4
measurements of variation within many different allele is associated with high lipid levels, predisposes to
species. Uniqueness can not be assumed or dictated cardiovascular diseases in middle-age, and Alzheimer’s
by arbitrary definitions. Sometimes researchers define dementia in old age. The APOE*4 allele shows a
a trait in a manner that precludes it from applying to decreasing frequency with increasing age through at
more than one species. Such definitional fiats hinder least the eighth decade of life. Although some associ-
comparative research in LH evolution. In addition, ations are similar, multiple different alleles at single
some LH associations observed in modern populations loci and variable haplotypes are associated with
may not have been crafted by NS. Rather they may extended longevity in different human populations
represent only current bioculturally constructed cor- in variable environments and cultures. Such a high
relations. That is, evolutionary origins of some LH degree of variation defies attempts to identify species-
traits may be unrelated to current patterns and distri- wide genetic modulators of senescence, although some
butions, representing instead selective pressures on must exist.
other traits or at previous points in human evolution. Associations with longevity suggest that many
The human genome project shows that only about alleles may similarly predispose to long-term survival
23 000 segments of DNA code for proteins in humans as does APOC3–641CC. Besides specific alleles,
(http://www.ornl.gov/sci/techresources/Human-Genome/ epigenetic regulation of gene expression affects mul-
project/info.shtml). Subsequent research indicates tiple loci (Jaenisch and Bird, 2003). Epigenetic alter-
that variable reading frames, pre- and post-translation ations affecting gene regulation occur during
editing, and different lengths of final polypeptides embryonic and fetal development, but may continue
throughout life as cellular mitosis replicates imprinted 58 and females 53 years (without observable meno-
loci (Barker, 1998; Cameron and Demerath, 2002; pause and an interbirth interval of 9.3 years). Survival
Kuzawa et al. 2005). Multiple epigenetic factors influ- through 5–6 decades, about a 30–35 year female repro-
ence health and life span. Associations of diet with ductive span, and multiple birth cycles is the basic LH
cancers and the metabolic syndrome and of smoking pattern among not only living large-bodied apes, but
with lung cancer are examples. All cells have multiple, many large-bodied mammals. Among men a 60-year-
often overlapping, and highly conserved housekeeping plus reproductive span, highly variable RS, high pater-
gene systems (e.g., albumin, ubiquitin, SOD, uric acid, nal PI, extended life spans, and survival past 7 decades
glutathione, and other antioxidants) (Eisenberg and of life are not shared with other large-bodied primates,
Levanon, 2003). Proteolytic systems, for example the nor are life spans of 100þ years and female survival to
proteasome, are important for cellular housekeeping. twice their age of last menses. Along with altricial
The proteasome degrades normal, misfolded, and offspring and high PI, these traits differentiate humans
oxidized proteins recycling their amino acids. It also from other hominins and hominoids.
degrades old proteins that accumulate in cells with Others have identified suites of unique human LH
age. Both in vitro and in vivo, senescent alterations characteristics (Shea, 1998; Smith and Bogin, 2000;
are correlated with impaired proteasome function Carey and Judge, 2001; Crews, 2003). Humans are
(Chondrogianni and Gonos, 2005). Proteasome generalists with some LH traits linking them to other
function regulates cellular homeostasis, helping to mammals, nonhuman primates, and extant and extinct
determine cellular senescence along with hundreds of hominins and hominoids. Evolutionary and allometric
other loci. constraints on the size of ovaries and number of avail-
able primary oocytes may lead to reproductive decline
with increasing age among all large-bodied mammals
Uniquely human life history traits
(Jones, 1975; Graham et al., 1979; Austad, 1994; Leidy,
Humans, like a number of other mammalian and 1994; Packer et al., 1998). Although some have
nonmammalian species show long lives. Comparisons attempted to make a special case for human reproduct-
with other long-lived species are one avenue for deter- ive decline and menopause by suggesting it is uniquely
mining unique and conserved aspects of human LH human (Pavelka et al., 1991; Turke, 1997; Hawkes
(Austad, 1997; Carey and Judge, 2001; Crews, 2003; et al., 1997, 1998), oocyte depletion over the life course
Austad and Fischer, 2005). Concepts such as a appears universal among female mammals (Graham
minimum necessary life span (MNLS: the amount of et al 1979; Leidy, 1994; Austad, 1997; Packer et al.,
time members of a species must survive to complete 1998). Austad (1994, 1997) describes reproductive
the “necessary tasks of life” as described by Weismann decline with increasing age among mammalian
[1881–1889]: gestation, growth, development, matur- females in such a fashion that one must conclude it is
ation, and reproductive effort), PI, and the costs of a pleisomorphic LH trait (see also Packer et al., 1998).
reproduction help focus this research. Elsewhere, we The main reason few female mammals show meno-
estimated a MNLS of about 45 years for humans and pause as currently defined is that few commonly sur-
about 35–42 years for chimps and gorillas (Crews, vive past their fifth decade of life, at which age almost
2003; Larke and Crews, 2006). Based upon Weismann’s all women are postmenopausal (see Figure 3.5 in
(1881–1889) concepts, a MNLS is similar to a Crews, 2003, p. 114).
Darwinian necessary life span. Similar to oocyte depletion, gestation lengths of
One woman already has lived three times the esti- about 9 months and completion of 95% brain growth
mated human MNLS (about 122.5 years). As yet, no by about 5–6 years are shared among living large-
chimp or gorilla has doubled their estimated MNLS. bodied apes. These commonalities suggest similar trait
However, the chimp who played Cheeta in the 1950s states may have characterized earlier hominins and
Tarzan films celebrated his 75th birthday on April 9, hominoids, perhaps representing basic large-bodied
2007. Among other large-bodied apes, on December 22, ape characteristics. Gestation length may be a symple-
2006, the world’s first captive-born gorilla (Colo) cele- siomorphic or synapomorphic LH trait within the
brated her 50th birthday at the Columbus Zoo (Colum- large-bodied ape clade. Elephants show longer gesta-
bus Dispatch, Ohio); on January 17, 2009 the oldest tion lengths, while marsupials have utilized shorter
male gorilla in a North American zoo (Timmy) cele- gestation lengths and pouches for extended infant care.
brated his 50th birthday at the Louisville Zoo (Colum- Such examples show that gestation length is an evolu-
bus Dispatch, Ohio); the world’s oldest captive tionarily malleable trait. Both human and marsupial
orangutan (Nonja) died at age 55 in December 2007 newborns are altricial. Evolving hominins and marsu-
at the Miami Metropolitan Zoo. Based upon estimated pials may have faced a similar problem – gestating
ages in a wild population observed over 32 years, Wich neonates in a limited amount of time – and hit upon a
et al. (2004) suggest orangutan males may survive similar solution, altricial newborns. Although their
developmental processes are distinctive, their solution, subsistence strategies practiced by each today likely
high PI postbirthing, is the same. Sociality and food reflect the unique and marginal subsistence strategies
sharing characterize many animal species. However, adopted by each in the late Miocene (Leigh, 2004).
they are not associated with extended life spans in Rounding out the suite of coadapted human LH
most. Extended life spans and multigeneration social traits are provisioning and care of nonkin, constant
groups are shared by humans, whales, elephants, food-sharing, and shared childcare (Crews, 2003,
chimps, gorillas, lions, and other social animals. 2005a; Crews and Gerber, 2003; Bogin 2009; Crews
Neither is uniquely human, both are pleisomorphic and Bogin, 2010). Modern-day humans are not exact
and synapomorphic mammalian LH traits. copies of earlier hominins and simple linear models
Humans invest early in life in their neurological based upon earlier forms poorly fit LH traits of extant
development by slowing their somatic development in primates, as do models based upon extant human for-
utero and producing secondarily altricial offspring agers poorly fit our ancient ancestors (Crews 2003,
(Smith, 1989). Born less physically developed, com- 2005a; Crews and Gerber, 2003). Earlier hominins did
pared to other large-bodied apes, humans require an not possess the current suite of human biocultural
extended growth period. Investments in neurological adaptations or our highly constructed niches and
tissues in utero and the first five years of life delay built environments. Additionally, the four extant
physical development. Altricial newborns, early neuro- large-bodied ape species are not an ideal comparative
logical development, and slow physical development sample of all large-bodied primates that ever existed
require late attainment of reproductive maturity com- for extrapolating Hominin evolution. They are just
pared to more rapidly developing large-bodied apes the ones who managed to survive into the present due
(Crews, 2003; Crews and Bogin, 2010). They also neces- to their adoption of unique subsistence strategies and
sitate extensive postweaning PI, thereby extending the LH patterns (Leigh, 2004 presents some possible
human MNLS. Slow developing secondarily altricial reasons). All four have followed separate evolutionary
offspring with early neurological development are pathways since bipedal apes formed their own lineage
uniquely human, an autapomorphic trait (Smith, some 7 mya.
1989; Peccei, 1995; Crews, 2003; Crews and Bogin,
2010). Secondarily altricial offspring are not seen in
Human life span
any other primate genus or species. These secondarily
altricial offspring are the basis of human LH evolution Based upon recovered burials and bioarchaelogical
and likely evolved with bipedalism and culture. Thus, reconstructions, Neolithic agriculturalists averaged
they require their own evolutionary explanation per- about 25 years of life. However, nineteenth-century
haps as a response to early bipeds’ limited pelvic width. industrialists could expect to survive about 45 years.
Freeloading altricial offspring are dependent on their In some modern populations, women average 85 years
parents’ abilities to provide continual PI over 15–20 of life, while men approach 80 years (Crews, 2005b).
years to offspring. Although PI occurs in all primates, Based upon estimated ages and survival patterns
its expansion to 15–20þ years is uniquely human. observed in living foraging/hunting populations, some
Modern humans also show adaptations in their gut suggest that once people survive childhood and their
morphology that differ from other large-bodied apes. second decade of life (to age 20 years) in such settings,
Other apes have their greatest gut volume in their they are likely to live into their 5–6th decade of life
colons, 45%, with only 14–29% small intestine (Milton, (40–50 years) (Hawkes et al., 1997, 1998; Carey and
1999). In humans, 56% of the total gut is small intes- Judge, 2001). Since the late Paleolithic, it is likely that
tine, while the colon accounts for only 17–23% (Milton, in most human groups some individuals may have sur-
1999). Based upon gut proportions, large-brained vived to complete 50 years of life or more. Nevertheless,
hominins adapted to high calorie diets digested mainly it is unlikely that many survived to 70 or 80 years; ages
in the small intestine. Most other large-bodied apes that few survive to today in many populations. Among
favor low-energy foods digested mainly in the colon. preagricultural groups of foragers, gathers, and hunters
Humans show greater plasticity in diet than other of the Paleolithic. Among preagricultural groups of
large-bodied apes. Their morphology supports the foragers, gathers, and hunters of the Paleolithic with
high-energy diet model of hominin evolution (Leonard, small local populations (N 500), it is not probable that
2002; Aiello and Wells, 2002), as do isotopic analyses of many survived even to their 50s. Estimates of survival
human remains (Sponheimer and Lee-Thorp, 1999). probabilities based upon estimated birth and death
Early Homo and later humans likely relied upon a rates among today’s foraging populations are not
variety of protein-rich foods as our modern LH pattern reliable. Actual birthdates seldom are known and data
developed; likely including easily obtained marine for constructing stable life tables are not available
resources (Kingdon, 1993). Only four great ape species for recent generations. Multiple external factors influ-
survived the Miocene ape extinction. Different ence such estimates. In contemporary cosmopolitan
settings, life expectancy exceeds 85 years among women entered into multiple regression models with age at
in only a couple of settings (Sweden and Japan) (Crews, first birth and age at mean childbearing, wealth’s effect
2005b; Larke and Crews, 2006). Some expect that max- on life expectancy reduces below statistical signifi-
imum life span will achieve 130–150 years by the mid cance. These results support suggestions by Crews
twenty-second century. A total wager of $300 between (2003, 2008; see also Larke and Crews, 2006; Bogin,
two well-known gerontological researchers, Steven Aus- 2009; Crews and Bogin, 2010) that later reproduction
tad and S. Jay Olshansky, in 2000, was widely reported. leads to increased RC and, ultimately, greater longev-
Austad expects someone alive today to survive over 14 ity. Across nations, delayed reproduction is associated
decades of life. If someone does, in 2150 his heirs will with longer life spans, suggesting that accumulating
receive the original wager and accumulated interest; if resources before reproducing produces greater RC.
not, Olshansky’s descendents win. This bet is significant High correlations of per capita income and mean
not only for what it says about predicted life expectancy age at first birth with life expectancy suggest that cul-
in the future, but also for what it implies about PIs in tural mechanisms provide opportunities to accumulate
future descendents by provisioning them via social RC and increase women’s reproductive opportunities
structures current in modern societies. In a recent at later ages. More benign, culturally constructed
report, Vaupel and colleagues (Christensen et al., 2009) environments lead to greater longevity by providing
suggest that if current trends continue, those born since women opportunities to increase their RC and their
2000 in cosmopolitan settings may achieve an expect- RS at later ages.
ation of life of 100 years.
Benign/cushy environments
Reproduction and life span
Human niche construction has created built environ-
Across human populations, the number of offspring ments for humans to reside and reproduce in for over
successfully birthed and reared to reproductive age 200 000 years (Odling-Smee et al., 2003; Crews, 2007,
varies positively, negatively, and not at all with longev- 2008; Crews and Bogin, 2010). Built environments
ity of women (Larke and Crews, 2006). Confounding allow people to live longer than ever before. Today’s
arises partly because both early and late fecundity are constructed environments allow humans to retain
associated with longevity, while total parity correlates their high functioning stress responses, immune, and
poorly with longevity (Larke and Crews, 2006). Vari- housekeeping systems well into their later years. A less
able associations of RS with longevity in women indi- positive result of constructed environments is that
cate multiple confounding factors (Larke and Crews, children in modern environments have high asthma
2006). For one, RS is determined less by fecundity, and and allergy rates. Exposures to pathogens and allergens
more by the quality/quantity of PI a women has to among individuals growing and developing in less-
invest in offspring. Human PI is more complex, exten- constructed environments may protect children
sive, and longer lasting (both relatively and absolutely) from such aliments. Modern urban slums may be
than for any other mammal. This supports a model “dirtier” and produce more infections and parasitic
that human LH coevolved with altricial offspring exposures than traditional farms and tropical settings.
and their need for extensive long-term PI. Shaped In cosmopolitan settings, less exposure to childhood
by biocultural factors, this need influenced all of diseases produces fewer immune responses and less
human physiology, LH variation, reproduction, senes- inflammation, contributing to retention of RC and
cence, and patterns of longevity (see also Crews and extended life spans (Crews, 2003, 2007, 2008; Drenos
Bogin, 2010). and Kirkwood, 2004; Finch and Crimmins 2004;
Analyzing wealth, longevity, reproductive, and Crimmins and Finch, 2005, 2006; Finch, 2005; Arking,
other LH variables, Larke and Crews (2006) showed 2006; Drenos et al., 2006).
that resources and the timing of reproductive events Well-nourished humans living in built environ-
significantly influence life expectancy. Wealth and age ments experience more benign living conditions than
at menopause correlated, while mean age at childbear- did their evolutionary forbearers. Laboratory, domesti-
ing did not significantly correlate, with life span. When cated, some island, and provisioned animal popula-
entered jointly in a regression model with age at first tions live better than their wild-living counterparts
birth and wealth, mean age at childbearing signifi- and less isolated populations. Benign settings provided
cantly positively predicts life expectancy. Colinearity opportunities for slowing senescence and enhancing
with mean age at first birth partly explains reports that longevity not available in more stressful environments.
mean age at childbearing is associated with longevity. Large increases in life span should not occur in high
Across national populations, the strongest correlates stress settings (Crews and Bogin, 2010). In such cir-
with life expectancy are wealth and age at first birth cumstances, organisms are frequently at or close to
(see Figures 2 and 4 in Larke and Crews, 2006). When their limits of survival, metabolic efficiency is at a
premium, and calories are best invested in reproduct- mortality and increased longevity. Inflammation is
ive effort (Parsons, 2002, 2003). Multiple genes for described as the “fire of frailty” (Walston and Fried,
cellular stress resistance, some predisposing to high 1999; Fried et al., 2004; Walston, 2005). Reducing life-
metabolic efficiency, enabling adaptation to energy- long inflammatory responses reduces secondary som-
poor environments, were adapted to harsher environ- atic damage, thereby improving RC and stamina.
ments with different selective pressures than prevail Caruso et al. (2005) suggest individuals genetically pre-
today (Parsons, 1996, 2002, 2003; Crews, 2003, 2008; disposed to weak inflammatory activity have a better
Arking, 2006; Drenos et al., 2006). In natural-living chance of living longer, provided infectious diseases do
populations, high vitality, stress resistance, and resili- not kill them. Variable alleles at multiple cytokine loci
ence enhance RC and survival, and continued survival influence the type and intensity of immune–inflamma-
depends upon substantial investments in allostatic tory responses, thereby affecting individual life expect-
responses. Genes for stress resistance, immune compe- ancy. At least one proinflammatory protein (APOE4) is
tence, and energetic and metabolic efficiency select- associated with earlier mortality among middle-aged
ively advantaged in environments of evolutionary and older adults. It appears that cushier environments
adaptation underlie modern human allostatic pro- with fewer pathogens and genetic predispositions
cesses. Today LH and longevity vary with ecological to weaker inflammatory activity jointly predispose to
circumstances. As culturally based niche construction longer life.
created cushy built environments, extended life spans Cohort morbidity phenotypes also may explain sea-
evolved in hominins. Similarly, only after defenses sonal variation in mortality (Finch and Crimmins,
against predation (i.e., large body size, body armor) 2004) in agricultural populations. Agricultural diets
were established did extended life spans appear in have ratios of omega-6 to omega-3 fatty acids (2:1) that
whales, tortoises/turtles, sharks, and elephants. differ from the diet proposed for ancient hominins
Older humans express their innate inclinations (10:1) (FAOUN/WHO, 1980). An altered omega-6
toward slower senescence and later mortality when to omega-3 fatty acid ratio from agricultural diets
living in modern-day cushy environments (Perls 2001, may produce nutritional inflammation. Conversely,
2006; Crews, 2005a, 2007, 2008; Drenos and Kirkwood, by increasing access to fresh fruits and vegetables
2004; Drenos et al., 2006). A “late-life” phase of LH throughout the year, agriculture may have contributed
following the senescent stage may occur among some to reduced stress from ROS and deficiency diseases
species, laboratory organisms, and very old humans, in and slowed some senescent processes.
cushy/benign environments (Rose et al., 2005a; Drenos
et al., 2006; Rauser et al., 2006). Social inequality likely
increased as the Neolithic revolution led to settled agri- DISCUSSION
culture and large-scale niche construction. Not all par-
ticipate equally in benefits from cushy environments. Humans, like all living beings, resulted from evolution-
Inequalities within cosmopolitan societies and ary processes by which radiations of earlier taxonomic
between them and traditional ones contributed to the groups created new ones. As the kingdom Animalea
rapid spread of the third epidemiological transition arose from earlier precursors, basic aspects of cellular
worldwide (Armelagos et al., 2005). Variable disease function were highly conserved through successive
patterns and life spans even among individuals living radiations. The same evolutionary forces shaped rock-
in the same environment reflect underlying demo- eating lichens, rock lobsters, rock-tool makers, and
graphic and physiological heterogeneity. rocket scientists. They also lead to social organisms,
nest builders, niche constructors, food sharers, nut-
crackers, fire starters, and both microbial and human
Frailty and inflammation
wine and cheese makers. Evolution produced multiple
As cushier environments developed over recent human species dependent upon complex patterns of food
history, reduced disease exposures were a cohort phe- acquisition – ants, bees, chimpanzees, humans, lions,
nomenon (Finch and Crimmins 2004; Crews, 2005b). wild dogs – using the same basic DNA and cellular
Swedish demographic data from 1751 to the present structures. This is why animal models and their rates
show that low early life mortality rates are associated of senescence reveal biomolecular strata occurring
with low adult mortality and greater longevity of the within human cells and somas that lead to biological
same cohort (Finch and Crimmins, 2004). This may be senescence.
a general population phenomenon (Crimmins and Short-lived laboratory organisms are incompetent
Finch, 2006). Finch and Crimmins (2004; Crimmins at successfully aging (Austad, 2003). Still, their DNA,
and Finch, 2005, 2006) suggest reduced lifetime expos- proteins, macromolecular structures, and processes of
ures to infectious diseases and inflammation contrib- cellular degradation are similar to those of most organ-
uted to large-scale historical declines in old-age isms. Drosphilia show broad additive and nonadditive
genetic variance for LH traits, ranging from ages at studies, e.g., Washoe, and those like Cheeta, Timmy,
first reproduction and intrinsic dysfunction to fecund- and Colo. Learned, shared, adaptive, and accumulated
ity and life span (Arking et al., 2002). Research on CR behaviors and beliefs (culture) drive humans to create
rodents shows that a nutritionally adequate but CR microenvironmental niches suiting their current per-
diet slows LH, reduces age-specific fertility, and ceived needs and tastes. Most organisms must respond
increases somatic maintenance. Conversely, laboratory to more immediate evolutionary pressures driving
mice eating energy-rich ad libitum diets show more their behavior, form, and function. Humankind uses
rapid LH, early reproduction, and decreased life spans. extrasomatic mechanisms to maintain intrinsic integ-
Even among nonhuman primates, CR improves rity. Animal skins and fire reduced dependence on
immune function and reduces inflammation (Ingram physiological resources. Tools and fire increased the
et al., 2004, 2005; Nikolich-Zugich and Messaoudi, range of obtainable foods and relaxed selection for
2005). The laboratory environment differs from that large teeth and jaws. Each generation, NS favors indi-
of wild animals. Laboratory populations have fewer viduals with phenotypes that increase their likelihood
stressors than nonlaboratory. Calorie restriction gener- of producing and rearing fertile offspring in their spe-
ally extends mean and maximum life spans of labora- cific environment. Modern humans constantly adapt to
tory rodents, but it does not do so for the wild-born. a variety of culturally created microenvironments.
Laboratory experiments show that multiple biomole- Genetic adaptations of LH to these new environments
cular processes, for example telomere shortening and may be slow. Easier to detect may be developmental
replicative capacity in vitro and antioxidant levels, are changes that occur without genetic alterations through
related to but may not be directly responsible for in changes in hormonal release, timing, or response
vivo senescence. We expect multiple cellular processes (Finch and Rose, 1995; Crews and Bogin, 2010) and
to correlate with whole organism senescence because patterns of phenotypic plasticity exposed as response
most are secondary processes, having evolved within to changing environments (Weiss and Buchannan,
already senescing organisms. Others likely result from 2003; Hallgrimsson and Hall, 2005).
antagonistic pleiotropy, mutation accumulation, and
evolutionary inertia, representing ubiquitous senes-
Human life history plasticity
cence in living cells. At the cellular level, senescence
reflects the loss of cellular integrity that results from Human developmental milestones and the timing and
ROS, mutation, DNA and protein errors, loses of regu- pattern of LH events are plastic (Finch and Rose, 1995;
latory, repair and housekeeping functions, immunity Barker, 1998; Bogin, 1999; Cameron and Demerath,
and self-recognition systems, telomere shortening and 2002; Crews, 2003; Finch and Crimmins, 2004; Weiss
lack of replacement of cells, and waste accumulation, and Buchannan, 2003; Hallgrimsson and Hall, 2005;
changes that characterize all aging cells. Human sen- Kirkwood et al., 2005; Crews and Bogin, 2010). To
escence begins with these same biological processes. some degree, the mid-childhood and adolescent
Over evolutionary time humans developed additional growth spurts are genetically programmed. However,
protections against such senescent alterations, they are still sufficiently flexible that their timing, dur-
allowing them to show a unique pattern of senescence ation, and rapidity vary across populations (Bogin,
and LH. Nevertheless, their underlying biology 1999; Crews and Bogin, 2010). Flexibility is the rule
remains that of a large-bodied mammal and ape. The rather than exception in human LH milestones, first
bioculturally constructed niche modern humans have and last menses, age-at-first birth, age at death, and the
created protects them from many extrinsic stressors point of MRP (Larke and Crews, 2006). Using cultur-
experienced by other species and previous hominins. ally derived adaptive strategies humans change their
This allows those with intrinsic stamina and RC to environments and allow their somas to respond to new
express predispositions to longevity. Phenotypes less and old stressors in different ways (Baker, 1984).
prone to stress-related, environmental, and intrinsic Cultural processes lead to animal domestication,
damage, biological wear and tear, and with high increasing the general availability of protein and fats
immune competence and mechanical reliability may (Larsen, 2003). This may have led to increased height,
now express their predispositions and live long lives. weight, and improved nutrition. Animal domestication
also brought novel infectious diseases (zoonoses) to
humans, increasing frequencies of alleles promoting
The human constructed niche and longevity
disease resistance. Animal and plant domestication
Humankind currently lives in constructed niches and and, subsequently, agriculture exposed humans to
built environments different from those of their ances- more than just new nutritional stresses. Population
tors, nonlaboratory organisms, most nonhuman pri- density increased and permanent settlements followed
mates, and nondomestic animals. Exceptions include increased availability of calories from agriculture.
some hominoids raised by humans during language This created an ecological setting wherein infectious
diseases and nutritional deficiencies dramatically maintenance, development of RC, and additional
increased (Larsen, 2000). As population densities and reproductive effort (Crews, 2003; Bogin, 2009; Crews
trading networks expanded, infectious diseases flour- and Bogin, 2010). As RS and fitness became dependent
ished and spread in villages, towns, and cities that upon learned activities and social relations (culture),
developed (Fenner, 1970). Skeletal remains suggest biocultural selection pressures for neurological devel-
measures of health declined following the innovation opment likely increased predispositions toward pro-
of agriculture until recent epidemiological transitions cesses that enhanced mental abilities. Based upon
(Larsen, 2000; Howell and Pfeiffer, 2006). available data, Homo ergaster may have birthed less
Human LH patterns respond to culturally derived precocial more altricial young than did earlier homi-
adaptive strategies. As humans created new microen- nins. Altricial human infants require high postgesta-
vironments within which NS and developmental plas- tional PI to support their brain and somatic growth
ticity occurred, they exposed a reservoir of genetic and and development. Culturally constructed environ-
phenotypic plasticity for LH. In the classic Livingsto- ments provide a safe haven for altricial offspring to
nian model, culturally derived behaviors allow humans not only grow and develop, but to be a viable ESS
to change their environment, eliminating, creating, and (Crews, 2003; Odling-Smee et al., 2003). Without a
altering selection pressures on themselves (Livingston, culturally constructed environmental niche in which
1958; Baker, 1984). As cultural forces created cushy to survive, humankind’s altricial offspring may not
living environments, selection relaxed for some traits, have been an ESS. Human encephalization seems to
created new stressors, and allowed a fuller expression have followed cultural developments toward more
of human developmental and LH plasticity (Crews, stimulating environments with fire, tools, social activ-
2007). ities, and complex social relationships. Laboratory
experiments with rodents demonstrate that more com-
plex (enriched) environments lead to more highly net-
Culture, diet, and life history
worked brains. More highly networked brains seem to
Large-brained neonates and toddlers require calories work in ways considered more intelligent by humans.
and nutrients beyond what is provided by diets of other Animals with more networked brains solve experimen-
large-bodied apes (Aiello and Wells, 2002; Leonard, tal tasks considered relevant to humans more rapidly.
2002). One cultural development, using fire, allowed Cultural developments, technologies, and processes
later Homo to consume toxic and difficult to process enriched and complicated the lives of evolving Homo
foods (Wrangham et al., 1999; Wrangham and Con- species, likely leading to a more intelligent longer-lived
klin-Brittain, 2003). Fire allowed intensive exploitation species
of old and new food sources and influenced human Many of today’s “modern” human populations tend
LH, skeletal biology, and digestive anatomy and physi- to consume only a small portion of edibles in their
ology. Humankind’s shorter colon than other apes environments. In today’s “more marginal” environ-
reflects bioculturally mediated selective pressures and ments, among predecessors of recently “modernized”
adaptation. Compared to other mammals and large- groups, and in more densely populated settings, a
bodied apes, modern human gut anatomy suggests broader array of edibles – larvae, insects, spiders,
modifications toward high throughputs of calorie- amphibians, reptiles, bats, and other less desirable
dense foods (Milton, 1999). Dietary changes toward animals and plants – are and were consumed. Archaeo-
meat eating and related technological innovations logically and historically, the amount of time and
coincided with brain expansion of the Homo species human energy devoted to food preparation in cosmo-
and our modern LH. Use of fire and meat consumption politan societies decreased as production increased. At
likely predisposed evolving hominins to small intes- the same time, rates of acute, infectious diseases and
tines of greater length as they digested more cooked childhood death rates declined. Among humans, time
and uncooked protein. Conversely, shorter colons of weaning is highly variable and related to multiple
likely followed diets with less fiber content. Cultural cultural and biological, and physiological factors. This
innovations improved physiological extractive effi- LH event is relatively easy to determine bioarchaeolo-
ciency compared to other large-bodied apes, and also gically (Larsen, 2000). Selective pressures on age at
allowed Homo species, including eventually humans, weaning apparently decreased as humans developed
to consume more calorie-dense and fewer low-calorie adequate and effective weaning foods. Availability of
foods (Larsen, 2003). quality weaning foods relaxed selective pressure on
New technologies and richer diets, freed somatic humans, releasing a mortality bottleneck limiting the
resources previously invested in food processing for proportion of children attaining adulthood. During
investments elsewhere. They were available for pro- much of early hominin evolution, those who survived
moting early neurological development, slow steady infancy likely faced high selective pressures after
growth over an extended growth phase, somatic weaning through puberty, as is seen in marginal
environments yet today. Those who survived likely humans and promoted modern human patterns of
possessed genetic predispositions promoting meta- LH, senescence, and longevity. Their general focus
bolic efficiency, efficient cellular housekeeping, less has been to obtain data from modern human popula-
inflammation, better DNA repair, and more efficient tions and extrapolate it into the past, with little
immune- and stress-responses. In such settings, those reference to comparative mammalian biology. These
attaining adulthood likely were hardier and better able extrapolations often are based upon selection extending
to combat prevailing environmental stressors. As child- longevity; an unlikely process if selection to lengthen
hood environmental assaults were reduced and less life is generally weak (Stearns, 1992; Carey and Judge,
energy was expended on daily food gathering and prep- 2001; Crews and Ice, 2010).
aration, resources were freed to be retained as RC Models based upon ecology observations of multiple
through adulthood and into late life. As life styles extant species and populations reveal a commonality
became cushier, humans produced and retained more of senescent processes across sexually reproducing
total energetic capacity over their early lives (Crews, animals (Jones, 1975; Gravilov and Gravilova, 1991;
2003, 2007; Drenos et al., 2006; Bogin, 2009; Crews and Charnov, 1993; Finch and Rose, 1995; Austad, 1997;
Bogin, 2010). Eventually, humans capable of retaining Arking et al., 2002; Crews, 2003; Holliday, 2004; Austad
RC into later decades of life showed increased life spans and Fischer, 2005). Human longevity is not unique.
(Crews, 2003; Bogin, 2009; Crews and Bogin, 2010). Whales, tortoises, sharks, and elephants are equally,
Evolutionarily the majority of life span extension or more, long-lived. Among chimpanzees, bonobos,
occurred over a relatively short time. It is not likely that gorillas, modern hunter-gatherers, foragers, and agri-
NS, as described in traditional or neo-Darwinian culturalists females migrate from their natal groups
models, greatly reshaped the distribution of senes- upon maturity. A behavior that likely characterized
cence-slowing or longevity-enhancing alleles in this earlier hominins and most modern humans. In such
period. Prior to historical times, evolutionary alter- social settings, grandchildren seldom see their mater-
ations in human LH occurred as cultural became nal grandmother. Thus, in most species, maternal
humankind’s primary adaptive response, biocultural grandmothers live in different locations and do not
feedback loops began determining the pace and pat- have opportunities to invest in their daughter’s grand-
tern of early LH, and altricial offspring became an children as some have proposed (Hawkes et al., 1997,
ESS. Altricial offspring require more time to grow 1998; Alvarez, 2000).
and develop. The need to nourish altricial offspring As parts of a species’ LH strategy, correlations
resonated throughout human LH, slowing the pace of among LH traits and their timing are expected, but
infancy, inserting childhood and adolescent periods correlation is not causation. Thus, ages at menarche,
and a puberty growth spurt, extending the ages of menopause, first birth, MRP, and the lengths of life
reproductive effort, and ultimately increasing selective span, growth span, infancy and childhood, and prere-
pressures on somatic maintenance (Bogin, 2009; productive and adult mortality rates should be correl-
Crews and Bogin, 2010). It is not likely that selection ated. Longer periods of growth and development
acted directly to increase human life span, because influence how investments in somatic maintenance,
“selection to lengthen life is generally weak” (Stearns, and the length of the reproductive phase are appor-
1992, p. 20; see also Carey and Judge, 2001; Crews and tioned. Events occurring in early life determine the
Ice, 2010). Rather, NS molds somatic responses to slow MNLS, the pace of growth and development, and the
and halt already existing processes of senescence. age at MRP, determining in part the reproductive span
Secondly, NS acts most strongly in early life and the and how long intrinsic adult mortality must be delayed
period of maximum reproductive effort. Its effects to allow sufficient reproductive effort to accomplish
on late-life are neither positive nor negative because the necessary tasks of life. Mammals require growth
late-life is beyond the purview of NS. and reproductive phases for a successful ESS. Over
time, somatic stabilizing factors evolved to protect
the developing human reproductive unit during its
Models for the evolution of human life history
maturation and reproduction phases in relatively
Models proposing “man the hunter” and “women the harsh environments. By slowing intrinsic senescent
gatherer” (e.g., Lee and DeVore, 1969; Lovejoy, 1981) processes they delayed somatic dysfunction and
were replaced by models suggesting that grandmothers altered intrinsic and extrinsic mortality rates, produ-
or future reproduction of relatives (Hill and Hurtado, cing correlations with other coadapted LH traits.
1991; Hawkes et al., 1997, 1998; Alvarez, 2000), adult As a population’s gene pool evolves toward a better
mortality (Charnov, 1993; Stearns et al., 2000), or fit to local environmental pressures, any alleles
learning and embodied capital (Kaplan, 1996; Kaplan improving survival during the growth and reproductive
et al., 2000, 2003; Bird and Bird, 2002; Kaplan and phases of life should be advantaged. Alleles with
Robson, 2002) altered evolutionary pressures on late-acting effects on survival, beyond the ages of
reproductive effort, whether positive or negative, are settings of early and late Homo species reducing intrin-
neither disadvantaged nor advantaged. Because their sic dysfunction and extrinsic mortality rates. These
frequencies are unaffected by NS, multiple alleles pre- changes allowed individuals to avoid extrinsic stressors
disposing to better or worse late-life survival, may be and retain RC into later life. They also provided a niche
active during the senescent phase of LH. As biocultural wherein secondarily altricial offspring could survive
processes continue to provide a means for older and prosper as an ESS. Secondarily altricial human
persons to increase their own RS and IF, additional newborns continue growth and development well into
advantages accrue to alleles predisposing to improved their second decade of life. The second decade of life is
late-life survival. Considering that having a significant the first decade of reproductive effort among other
number of elders in any one local population is a rela- large-bodied apes. Biocultural evolution during the
tively recent phenomenon (Caspari and Lee, 2004), it is earliest phases of life altered all later aspects of LH,
not likely that such alleles were greatly advantaged modulating growth and development, reproduction,
until the advent of modern humans. and length of life (Bogin, 2009; Crews and Bogin,
Across human populations, older surviving men 2010).
have more offspring than men who die at younger ages. Human LH, senescence, and longevity are based
Greater variation in male than female RS allows men upon a suite of characteristics – encephalization, non-
to benefit more from long life than women. There are genetically programmed behaviors as survival strat-
intrinsic constraints on completed fertility of women, egies, sociality, and group living – shared with many
but not men. This may be more relevant than meno- primate species (Shea, 1998; Crews, 2003). Parental
pause and grandmothers to life span and LH evolution investment, social groupings, incipient culture, group
in humans (Marlowe, 2000; Crews, 2003, 2008). hunting, group protection, and sharing of meat are all
Genghis Kahn and his male relatives are hypothesized seen among other large-bodied apes. As the hominin
to have contributed their Y-chromosome and to be the large-bodied ape clade evolved, several uniquely homi-
direct ancestors of about 8% of contemporary Chinese nin trends, beyond bipedalism and culture, emerged.
men living in central Asia (about 16.7 million or 0.5% Culture and hands freed from locomotion led to add-
of all living men) (Zerjel et al., 2003). Conversely, a itional uniquely human traits, extensive use of tools
significant number of men fail to ever sire children. and fire, niche construction, secondarily altricial off-
This may be related to why men may show lower rates spring, slow development to reproductive maturity,
of senescence at extreme old age than do women mutually supporting social networks of kin, and life-
(Gavrilov and Gavrilova, 1991; Carey, 1995; Graves long PI.
et al., 2006). Alleles predisposing to somatically com- In modern cosmopolitan settings, most women live
petent men likely were advantaged in environments to experience menopause; however, in the late nine-
of evolutionary adaptation. In today’s cushy environ- teenth and early twentieth centuries only 20% of Native
ments these competencies may be expressed as greater American, 30% of Black, and 60% of White US women
RC at older ages and longevity. survived to age 55, respectively (see Figure 3.5 in
Crews, 2003, p. 114). Even in the twenty-first century
many women in Third-world settings do not survive
CONCLUSIONS past menopause. It seems unlikely that many females
did so among earlier Homo species. Nor are life spans
Natural selection for longevity may not be the reason of over 50 years often observed among wild living non-
for modern humankind’s seemingly slow senescence. It human large-bodied female apes or mammals of
is unlikely that modern humans would senescence as known age. Ovarian depletion, reduced fertility in the
slowly in any of our ancestral environments as they do late fourth and early fifth decades, and menopause
in today’s constructed niches. That is, Cheeta would occur in all female mammals who survive sufficiently
never have attained 75 years in the wild. Humans con- long, past their fourth decade of life (Austad, 1994;
tinue to face high selective pressures, but today’s indi- Leidy, 1994; Rogers, 1993; Packer et al., 1998). Con-
viduals are descended from ancestors who were trary to several selective models of human LH, lifeways
reproductively successful in harsher environments. of modern-day traditional living populations are not a
Today, these pressures are avoided by living in built window on earlier Homo and human lifeways. Nor do
environments created as sociocultural adaptations to they represent the lifeways of hominins when our cur-
external stressors. Most current scenarios for human rent LH developed. Every extant population is exposed
senescence and longevity fail to consider these factors. to modern cultures, lifeways, and multiple outside
Contrary to many evolutionary models based on selec- influences (Crews and Gerber, 2003). Societies not so
tion for longevity, a biocultural model suggests that influenced prior to the arrival of missionaries and
cultural developments, niche construction, and cultur- anthropologists included residents of tropical South
ally derived adaptive strategies altered the ecological America and Africa and highland New Guinea at first
contact. Although isolated, none was struggling to feed extending well beyond those of other large-bodied apes
itself, suggesting little energetic trade-off between appear to be an epiphenomena of NS acting on aspects
reproduction and self-maintenance. They lived in of early LH, altricial offspring, slow growth, and an
highly integrated societies. They had sufficient free extended growth phase that stretched out the period
time to elaborate extensive social activities. Their tradi- for attaining MRP (Bogin, 2009; Crews and Bogin,
tional lifeways do not conform to evolutionary scen- 2010). This early LH is now played out in culturally
arios based upon scarcity of resources or difficult constructed environments that allow retention of RC
processing to extract limited resources as are reported and lead to somatic maintenance into the ninth, tenth,
among some modern-day foragers (Kaplan, 1996; and later decades of human life.
Kaplan et al., 2000, 2003; Bird and Bird, 2002).
It is unclear if late-life stages when both senescence
DISCUSSION POINTS
and mortality rates slow their increases exist among
multiple species. It is certain that no currently popular
1. The disposable soma theory for the evolution of
model of human LH evolution explains a mortality
senescence is based upon what aspects of repro-
plateau in the last decades of human life. Conversely,
ductive biology? How have recent developments in
biocultural evolution leading to the retention of som-
understanding the living histories of single-celled
atic resources over a lifetime of living in cushy environ-
organisms altered this view? How would you
ments is compatible with a late-life mortality plateau.
reframe this model in light of these new results?
Understanding human senescence and longevity
What are two mechanisms by which senescence-
depends as much on comparisons with short-lived
promoting alleles may be retained in the genome
and nonmammalian taxa, as it does on comparisons
over evolutionary time?
with other long-lived and mammalian organisms.
2. What methods might one use to measure pheno-
Increased focus on how biocultural influences on
typic aging and why should it be measured? What
humans changed survival probabilities and longevity
methods might one use to measure biological
will be a positive development toward understanding
senescence at the cellular level and why should it
LH evolution across all species.
be measured? What are some differences between
Understanding how modern humans became rela-
senescence and aging?
tively long-lived compared to other apes requires com-
3. Given what you have read and know of modern human
parisons with other primates, mammals, and life forms
life history and variation, describe how because
and examinations of across population human LH
humans are cultural animals their life history may
variation. Among humans RS, reproductive effort,
evolve differently from nonculture-using animals.
RC, stress resistance, life span, longevity, and senes-
4. What are some biological factors that pattern
cence are highly variable individual traits. Not even
life history (LH) of animals and mammals? Does
identical twins show the same ages at death and famil-
modern human LH show factors other than biology
ial correlations for longevity often are low. Mechanistic
that influence their LH? Are humans so unique in
models for human LH evolution often are retrospective
their LH that we need special models to explain
and do not account for the influences of biocultural
their LH evolution?
evolution. Biological processes contribute to human
5. Austad critiqued earlier definitions of senescence
senescence via mostly unknown genes and unidentified
and aging for not including any mention of repro-
physiological pathways. Pushed by the grand theory
duction and fertility. Why are reproduction and
of evolution by NS, existing models of human LH
fertility important for defining senescence and
evolution often lack mid-level theory, failing to identify
aging? What are the meanings of “age of maximum
or hypothesize genetic or physiological mechanisms,
reproductive potential” (MRP) and “minimum
or physiological pathways linking genes and LH. No
necessary life span” (MNLS)? How does the age of
system of accounting by which NS may tally the influ-
MRP influence the MNLS?
ences of epigenetic factors and learning or the future
RS of offspring and calculate the probability of grand-
offspring has been proposed. Clearly intrinsic factors ACKNOWLEDGEMENTS
acting throughout the growth phase influence adult
mortality and human life spans. Natural selection Sincere thanks to the editor Michael P. Muehlenbein for
likely acted on early LH factors linked to RS that also his efforts in bringing this comprehensive volume
improved resistance to extrinsic stressors, retention of together and inviting us to include this work. We also
RC, and ultimately extended life spans in culturally acknowledge the insightful comments and suggestions
created settings (Crews and Bogin, 2010). However, of two reviewers that improved this contribution.
NS may never have acted directly to extend human life Finally, we wish to thank Courtney McFadden and Rhea
span or postreproductive survival. Rather, life spans Alleyne for typing multiple versions of this manuscript.
Bogin, B. (1999). Patterns of Human Growth. New York:

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32 Evolutionary Psychiatry: Mental
Disorders and Behavioral Evolution
Brant Wenegrat
INTRODUCTION can play a role in treatment. Concepts explaining

social life seem especially suited to shed light on dis-
Since W. D. Hamilton’s seminal work on kin-selection orders with social precipitants, causes, consequences,
(Hamilton, 1964a, 1964b) advances in the field of and remedies.
behavioral evolution have changed our view of animal In this chapter, I review some of the efforts to
and human social behavior. A wide range of social understand mental disorders and possible treatments
behaviors – altruistic, co-operative, aggressive, paren- for them in terms of concepts drawn from behavioral
tal, and sexual – are now seen as products of past evolution, a field known as evolutionary psychiatry.
selective forces, many of which were generated by Authors and researchers working in this field employ
social interactions. Fifty years ago, it was possible five disparate paradigms (see Nettle, 2004). Although
for Behaviorists to argue that humans are blank slates the differences between them are sometimes ignored,
whose nature – if such exists – is wholly determined these paradigms have differing aims and relative
by cultural/environment forces. The most basic emo- strengths and weaknesses. Many debates in the field
tional attitudes – for example, sexual preferences and result from application of disparate paradigms to the
parental concern for children – were said to result same disorder. This chapter will cite examples from
from training and cultural expectation. That position each of the five major paradigms to illustrate their
is no longer tenable, in large part due to concepts differences, logic, goals, and weaknesses.
from behavioral evolution.
At the same time, important advances have been
made in psychiatry. Over the last 40 years, psychiatric THE ADAPTATIONIST PARADIGM
researchers have identified mental disorders that can be
reliably diagnosed, may affect Darwinian fitness, and are The adaptationist paradigm aims to view mental dis-
partly caused by genes. A large proportion of people in orders, their milder variations, or illness-related traits as
most or all societies suffer from one or another of these behavioral adaptations that confer or have conferred
mental disorders. The research on diagnosis culminated inclusive fitness benefits. Widely cited models of schizo-
in the 1994 publication of the Diagnostic and Statistical phrenia and schizotypal disorder, depression and mania,
Manual of the American Psychiatric Association, Fourth and anorexia nervosa illustrate the goals and pitfalls of
Edition, known as the DSM-IV, which lists objective this paradigm.
criteria for diagnosing disorders (American Psychiatric
Association, 1994). The DSM-IV criteria for specific
Schizophrenia and schizotypal disorder
disorders are described later in this chapter, along with
pertinent prevalence, genetic, and fitness data. To give According to the DSM-IV, schizophrenics suffer from
readers a better sense of some disorders, case examples social–emotional deficits (emotional flatness, apathy,
are given. loss of social interests), odd or magical thinking, and
Insofar as concepts from behavioral evolution can psychotic symptoms, such as hallucinations and delu-
explain human behavior, they might shed light on sions (American Psychiatric Association, 1994). Their
disorders like those in the DSM-IV (Troisi, 2005). speech and behavior may be eccentric, disorganized, or
These concepts deal with social life, social events, even unintelligible. The symptoms must cause social or
and experiences known to trigger disorders, or cause occupational impairment, have lasted for six months
them in some cases. Concomitant social deficits or longer, and not be attributable to another condition,
account for the disabilities resulting from these dis- such as drug abuse. A typical case of schizophrenia is
orders, and psychotherapy, which is a social process, described in Box 32.1.
551
552 Brant Wenegrat
BOX 32.1. A case of schizophrenia.
LN, a 41-year-old woman, had been normal until and returned to her parents’ home. Over the next 20 years,
adolescence, when she began to withdraw from friends and her delusions were generally controlled by medications, but
became increasing “odd” and emotionally inexpressive. she had no interest in meeting other people and didn’t like
She completed high school and was admitted to college, leaving the house. She never worked or dated. When her
but during her first semester she became convinced her elderly parents needed to sell their house, LN went to live
professors were trying to kill her. She thought students in with her sister, in another town. Her sister, who had two
her dormitory were spying on her, and that there were children, could not manage LN’s disruptive behavior and
coded messages about her in the campus paper. She had to place her in a group home for the mentally ill. LN’s
thought that campus football scores somehow foretold her maternal grandmother and a maternal aunt were also
future. She was admitted to the student infirmary and schizophrenic and a maternal uncle was thought to be
diagnosed with schizophrenia. LN withdrew from college schizotypal.
Schizophrenia runs in families (Gottesman and larger-than-family groups might be beneficial. Along
Shields, 1982). For example, first-degree relatives of a a similar line, Sullivan and Allen (1999, 2004) argued
schizophrenic (children or full siblings) are 10 times that individuals with schizoid personalities are some-
more likely to develop this disorder than individuals times better able to balance their own needs and inter-
drawn from the general population. If one identical ests against those of their social group, to which they
twin is schizophrenic, the chances are 50% that the other are less committed.
will also be ill. Relatives of schizophrenics are also at An advantage might also accrue from creative
increased risk for personality disorders that are thought eccentricity. The notion that there is a close relation-
to represent milder forms of the same trait or illness. ship between creative genius and madness goes far
Schizoid personalities, for example, are emotionally back in Western culture (Burns, 2006). In fact, while
flat and socially disengaged, but their thinking and schizophrenics themselves are not especially creative,
speech are normal. Schizotypal personalities are socially some of their healthy relatives do have unusual gifts,
disengaged, and in addition their thinking is odd or which might lead to increased fitness in some soci-
magical and they have strange beliefs (American Psychi- eties (Karlsson, 1966; Anthony, 1968; Heston and
atric Association, 1994). They resemble schizophrenics, Denny, 1968; Kauffman et al., 1979; Rabin et al.,
but lack the psychotic symptoms. A typical case of schi- 1979; Rothenberg, 1983; Ludwig, 1995; Nettle, 2001).
zotypal personality disorder is described in Box 32.2. In a sample of British adults, Nettle and Clegg (2006)
Schizophrenia and related personality disorders are showed that a measure of schizotypal eccentricity
referred to as the “schizophrenia spectrum disorders” correlates with artistic and creative activities, which
and are generally believed to be caused by multiple correlate in turn with numbers of sexual partners.
illness-promoting alleles, each of small effect, acting at Studies of the fertility of relatives of schizophren-
multiple loci (see Crow, 2007). Environmental insults – ics have had mixed results. Some show increased
such as in utero viral exposures – interact with genetic reproductive fitness, while others do not (Kendler
risks. The higher the dose of illness-promoting genes et al., 1998; Avila et al., 2001; Haukka et al., 2003).
and environment insults, the more likely an individual Proving increased fitness in families of schizophren-
will develop schizophrenia or schizotypal personality ics is an obvious first step in validating advantages of
disorder; the lower the dose, the more likely the person illness-related traits.
will be relatively normal. Stevens and Price (2000a, 2000b) hypothesized that
As one might guess from the case described in schizotypal oddity and eccentricity served an adaptive
Box 32.1, schizophrenics – especially males – living in function in early human groups, even if it is a handicap
modern societies have fewer children than average today. According to these authors, ancestral groups
(Bassett et al., 1996; Avila et al., 2001). However, if repeatedly grew to the point that they outstripped their
schizophrenia impairs reproduction, how do alleles resources, leading to in-group conflict. At such times,
that cause it maintain their place in the gene pool? schizotypal persons could catalyze group splitting.
Why don’t they disappear? Because of their odd, other-worldly manner and
One potential answer is that relatives of schizo- strange beliefs and convictions, schizotypal persons
phrenics with mild to moderate traits related to schizo- may take on cultic status in times of social stress. Such
phrenia might have selective advantages that offset the a person could form the nidus for an incipient new
handicaps resulting from full-blown illness. Selection group emerging from an old one.
against schizophrenics might be balanced by kin Although Stevens and Price (2000a, 2000b) cite stud-
advantage. Kellett (1973), for example, speculated that ies showing that schizotypal traits promote formation
schizoid personalities enjoy a fitness advantage in of cult-like groups, other research undermines their
some societies, in which weaker emotional ties to hypothesis. Modern-day studies of hunter-gatherer tribes
Evolutionary Psychiatry: Mental Disorders and Behavioral Evolution 553
BOX 32.2. A case of schizotypal personality disorder.
AH came to psychiatric attention for the first time in his late influence him, but he was able to keep a professional – if not
50s. He had been living with his elderly mother in her friendly – demeanor. After dropping off a passenger, he
apartment until her sudden death from a stroke. He had would “review” his thoughts to see that they hadn’t been
completed high school and two years of junior college altered by contact with other people. After AH’s mother
and worked as a cab driver for the previous 25 years. He died, the apartment manager – who had tolerated AH’s
had never married or had intercourse, and he had never had glaring, unpleasant manner for his mother’s sake – asked
friends or socialized, other than with his mother. He didn’t him to leave. AH created a disturbance and the police were
experience this as a problem. He felt uncomfortable having called. As part of the ensuing court process, AH was referred
passengers in his cab and feared they would try to cheat or for a psychiatric evaluation.
show that although group splitting can occur, it is an Pointing out that some depressive episodes are trig-
infrequent occurrence (Chagnon, 1979). When groups gered by real or threatened loss of social standing,
split, moreover, kinship – not cult beliefs – determine Stevens and Price (2000b) argue that depression is an
who joins which daughter group. Studies in Western adaptive strategy in that situation. By withdrawing from
societies show that people join cults because they are competition, the depressed individual avoids further
socially isolated, not because they are captivated by the conflict and losses. He or she submits to the fact he or
cult ideology or entranced by the leader (Galanter, 1978, she has failed, and ceases to struggle further. Depression,
1989; Wenegrat, 1989). Accepting cult ideology and the by this account, communicates submission. In a related
leader’s authority is the price paid for group membership, vein, Gardner hypothesized that depression manifests an
not the motivation. Finally, in his comprehensive cross- evolutionarily ancient “PSALIC,” or “Propensity State
cultural study of shamanism, I. M. Lewis found that Antedating Language in Communication;” a primitive
shamans in traditional societies are distinguished from signaling system, in other words (Gardner, 1988).
others by virtue of their excellent social skills, not by their Watson and Andrews (2002) suggest that depression
eccentricity (Lewis, 1971). Social skills, not eccentricity, evolved as an adaptive response to intractable social
are needed to establish a credible claim to cultic or problems. The mental effect of depression is to focus
magical powers. the individual’s attention on his or her problems. It also
sends a signal to potential helpers that more assistance
is needed. Since uninterrupted depression may even end
Depression and mania
in death, those who have an interest in the depressed
According to the DSM-IV, major depression is character- person’s survival are virtually extorted to offer increased
ized by depressed mood most of the day, diminished aid. Hagen (1999) made a similar argument regarding
interest and pleasure in usually enjoyable activities, postpartum depression. According to Hagen, postpartum
insomnia or excessive sleeping, agitation or mental and depression is a way that mothers signal their partners and
physical slowing, persistent feelings of worthlessness or other persons that they need assistance caring for their
guilt, impaired thinking or concentration, and frequent newborns.
thoughts of death (American Psychiatric Association, Individuals who have episodes of mania or hypo-
1994). Appetite may be increased or decreased, with mania – which usually alternate with periods of
consequent changes in weight, and sexual interest is depression – are given the DSM-IV diagnosis bipolar
diminished or lost. Depressed individuals may harm or disorder (American Psychiatric Association, 1994).
kill themselves. As is the case with schizophrenia, these Mania is characterized by an increase in energy,
symptoms impair social or occupational functioning and euphoria, high self-esteem and even delusions of
they cannot be accounted for by other disorders or grandeur, disregard for risks and consequent reckless
illnesses. Severely depressed patients may experience behavior, and initiation of projects that are patently
hallucinations or delusions with depressive themes; for unrealistic. A manic patient, for instance, may believe
example, they may hear voices condemning them and he or she alone has the answer to the world’s problems.
believe they are already dead. Depressive episodes may He or she may plan to run for President, spend all his
come and go, even without treatment, but generally money on campaign posters, attack the banker who
recur. A case of severe major depression without psych- refuses to finance his television adverts, and fight with
otic features is described in Box 32.3. policemen who are called to quell the disturbance.
Since major depression is partly caused by genes Hypomania is a milder form of mania, which doesn’t
(Sullivan et al., 2000) and leads to decreased fitness cause marked social or occupational impairment or
(Cuijpers and Smit, 2002), it presents the same conun- require hospitalization. Bipolar disorder is partly genet-
drum as schizophrenia: how are alleles promoting it ically caused (Craddock and Forty, 2006). Adaptationist
maintained in the population? models of low-level forms of mania mirror those of
554 Brant Wenegrat
BOX 32.3. A case of severe depression.

ME experienced his first severe depressive episode 2 years depressive symptoms returned. His ex-girlfriend – they had
after graduating from college, at age 26. This episode broken up six months before – saw he was depressed again
started after he failed to get a work promotion he and tried to get him back into treatment, but ME refused. He
expected. He was pervasively sad, he lost 20 pounds, he again stopped going to work, neglected his hygiene, and
lost interest in sports, sex, and friends, and he slept only started losing weight. He cried frequently and thought that
4 hours nightly, although he was exhausted during the day. he was worthless. His ex-girlfriend called ME’s landlord when
He was consumed by feelings of shame and he saw himself as he didn’t answer his phone for a couple of days. Using his
a failure and disappointment to everyone. After two months passkey, the landlord found ME lying on his bed,
of illness, he stopped going to work. His girlfriend eventually malodorous, disheveled, and emaciated. ME improved
got him to seek medical care. He recovered with dramatically after a month in the hospital. ME’s father and
antidepressants and psychotherapy. Three years later, sister had also been treated for depressive episodes, which
when he was off medications and out of therapy – the were not as severe as ME’s.
depression. According to such models, mania might be held belief that it has a long history, anorexia nervosa as
adaptive when social standing is rising (Gardner, 1988; it is now known first appeared in Western Europe and the
Stevens and Price, 2000a), and milder manic traits United States during the late nineteenth century, and its
may help individuals achieve positions of leadership subsequent prevalence has largely been determined by
(Gardner, 1982; Akiskal and Akiskal, 2005). cultural dictates regarding ideal weights (reviewed in
These models of mood disorders run counter to some Wenegrat, 1996).
of the data. Contrary to the notion that depression is a Beyond the obvious weak points of adaptationist
way of avoiding hostility, many depressed individuals models, some of which were cited above, the adaptation-
are markedly irritable (Painuly et al., 2005). Contrary to ist paradigm faces some general challenges. Firstly,
the notion that depression leads to assistance, depressed adaptationist models may not be needed or called for.
individuals are seen in a negative light (Coyne, 1976) and Since psychiatric disorders are promoted by many alleles,
lose important relationships (Reich, 2003). Moreover, each with a small effect size, persistence of alleles leading
Nettle (2004) points out that the high heritability of to mental disorders can be explained without recourse
depressive disorders, the tendency of depression to occur to putative positive benefits (Keller and Miller, 2006).
out of the blue – not in response to stressors, the chron- Occasional germline mutations can replenish any alleles
icity of the illness once it is established, the absence of lost due to mental illness.
concrete evidence that it serves a useful function, and the Secondly, even if risk alleles for psychiatric dis-
plethora of evidence for adverse fitness effects are incon- orders do confer positive benefits, the adaptationist
sistent with depression being a true biological adaptation. paradigm might focus too much on illness and illness-
related traits: Genes leading to mental disorders might
promote advantageous behaviors unrelated to illness
Anorexia nervosa per se or confer advantages in other realms entirely.
For example, a short allelic variant of the promoter
The adaptationist paradigm has also been applied to region of the serotonin transporter gene increases
anorexia nervosa, a disorder that occurs mostly in the risk of depression, especially following stressors
young women and is characterized by a preoccupation (Jacobs et al., 2006; Wilhelm et al., 2006), but seroto-
with thinness and a terror of becoming fat (American nergic dysfunction may lead to greater impulsiveness
Psychiatric Association, 1994). By fasting and exercising, and earlier reproduction (Stein, 2006). A considerable
anorexics reduce their weight to the point that they body of evidence suggests that immune system genes
stop menstruating and become temporarily infertile. may contribute to schizophrenia (Strous and Shoe-
Untreated anorexia may end in death from starvation. nfeld, 2006). If so, some genes that promote schizophre-
A typical case of anorexia nervosa is described in nia may protect their carriers against viruses, cancer, or
Box 32.4. Like schizophrenia, major depression, and autoimmune disorders. Neither of these possibilities
bipolar disorder, anorexia nervosa is partly caused by are captured by adaptationist approaches to mental
genes (Bulik et al., 2006). Several authors argued that disorders or illness-related traits.
anorexia nervosa is an adaptive strategy for suppressing
reproduction, when circumstances are such that repro-
duction would be disadvantageous (Wasser and Barash, THE ETHOLOGICAL PARADIGM
1983; Surbey, 1987; Voland and Voland, 1989). As the
case described in Box 32.4 illustrates, this model has Ethology is the study of species-typical animal behav-
to explain how an illness so devastating can possibly ior. Human ethology refers to the study of behaviors
increase fitness. Furthermore, contrary to the widely typical of Homo sapiens (Eibl-Eisbesfeldt, 1989) Being
BOX 32.4. A case of anorexia nervosa.

At age 14, SL was considered pudgy. She started dieting, on several occasions and was found to be anemic and to
and by her 15th birthday she was noticeably thin. Over the have electrolyte abnormalities. Her bones were starting to
subsequent six months her weight continued to drop. At lose calcium. She weighed herself numerous times each day.
15½, she was 5’4” tall and weighed only 95 pounds. Her If her weight was lower, she felt ecstatic; if it was even
periods, which had started when she was thirteen, had slightly higher, she felt panic-stricken. She was afraid the
stopped some months before. In spite of her weight loss, slightest gain would lead to loss of control and to her
she saw herself as fat and would eat only diet food or salads becoming obese. When her weight dropped below 90
with no dressing. If allowed to, she would jog or use a pounds, SL was hospitalized and given nutrition through a
stationary bicycle for two to three hours daily. She fainted naso-gastric tube.
species-typical, such behaviors must result from the failure of a particular piece of the species-typical human
action of human genotypes in “normal” human envir- behavioral repertoire. Individuals with these disorders
onments. The ethological paradigm asks if signs and fail to fully engage in larger-than-family social groups
symptoms of mental disorders can be described effi- or to adopt their worldviews. They are generally normal
ciently by reference to human ethology. children, but when they reach adolescence – when
For example, one typical human behavior evident normal individuals orient themselves in larger-than-
in all cultures is to form close-knit social groups, family social groups – their social disengagement and
members of which are considered superior to outsiders their inability to learn subtle social rules and the consen-
(Tinbergen, 1976). In traditional tribes, for instance, sual worldviews of these larger groups first become
outsiders may be killed, especially if they are male. apparent. They may seem odd to others. They start to
The name of the tribe is frequently the term for feel uncomfortable outside their families of origin and
human beings (Berger and Luckmann, 1966). In such fearful of others within the groups they might join.
societies, small groups are composed of kin. Early Like some adaptationist models described in the
studies of hunter-gatherer tribes, for instance, showed previous section, this ethological model locates the
that members were only slightly less related on average pathology of the schizophrenia spectrum in larger-
than first cousins (Chagnon, 1979). In such conditions, than-family groups, but it does not presume that the
positive attitudes toward group members and invidi- deficit is or has been adaptive. The emphasis is on
ous attitudes toward outsiders are consistent with kin placing deficits seen in illness in the context of the
altruism. normal human behavioral repertoire.
Persons in modern societies may not kill outsiders
(though, sadly, they sometimes do), but they nonetheless
Attachment theory
cohere in small, invidious social groups. Spontaneous
group formation and resultant outward hostility has John Bowlby, whose “Attachment Theory” has had a
been shown in psychology laboratories, occurring major impact in psychiatry, studied relationships
among total strangers (Tajfel and Billig, 1974; Tajfel, between caretakers and infants, and infants’ responses
1981, 1982). Formation of social groups is thought to to being separated (Bowlby, 1969, 1973, 1980). He dis-
have protected early hominids from predation and early covered that infants separated from their principal
humans from competing groups, and to reflect innate attachment figure, who don’t have other familiar
psychological and behavioral factors (Alexander, 1979). attachment figures available, engage in stereotyped
Human social groups, even those created in the emotional displays. In the first, or “Protest” phase,
laboratory, develop consensual worldviews (reviewed in the infant cries or screams and attempts to follow or
Wenegrat, 2001). Reality, in other words, is socially con- find the missing attachment figure. This phase may
structed within the human group. Lumsden and Wilson last several days. If the caretaker doesn’t return, the
(1981) argued that group enculturation was probably “Despair” phase will set in. Active efforts to signal or
highly adaptive and led to the selection of conformity- find the caretaker cease, and the infant becomes
promoting genotypes. The neurological basis of social apathetic and socially withdrawn. The third, or
imitation is only now beginning to be understood “Detachment,” phase starts after separations lasting
(see Meltzoff and Prinz, 2002). In real groups and in two weeks or more. The child in this phase is docile,
groups created in laboratories, individuals who fail to apathetic, and detached from his or her social envir-
conform may be seen as outgroup members and become onment. This phase may last a long time, even if the
the object of aggression. attachment figure reappears.
Many signs and symptoms of schizophrenia spec- Bowlby noted the similarities between children’s
trum disorders manifest failure of normal group- attachment behaviors and separation responses and
orientation (Wenegrat, 1990a). That is, they represent those shown by immature primates. He considered
556 Brant Wenegrat
attachment behaviors and separation responses as evolved to solve social problems (Dunbar, 1998),
evolved behavioral patterns common to humans and capacities like those listed here may depend on evolved
primates. neural circuitry specialized for each purpose. According
The resemblance between the phases of the separ- to researchers broadly identified as Evolutionary Psych-
ation response and certain types of depression were ologists, specialized mental capacities that evolved
evident to Bowlby. The Protest phase, for instance, for particular functions – or innate psychological
resembles agitated depressions in adults. The Despair modules – comprise the basic structures of human
and Detachment phases resemble “retarded” depres- mental life (Barkow et al., 1992; Hirschfeld and Gelman,
sions, which are depressions characterized by psycho- 1994; Pinker, 1997; Cosmides and Tooby, 1997). The
motor slowing, apathy, and withdrawal. This led to the innate-module paradigm asks if mental disorders can be
hypothesis that adult depression is a manifestation of understood as dysfunctions of discrete evolved mental
early attachment behaviors somehow reactivated, and modules.
to the hypothesis that early attachment disruptions For example, studies have shown that humans more
predispose to later depression. The latter hypothesis readily learn fear responses to objects and situations
has found some empirical support, though depressive that posed threats to our ancestors – such as snakes,
illness also occurs in people who had no attachment spiders, threatening animals, darkness, and high spaces –
disruptions (Gilmer and McKinney, 2003). than to far more dangerous modern-day objects and
This model of depression resembles an adaptation- situations, such as guns, knives, and high-speed driving
ist model that treats depression as a response to loss of (Marks, 1987; Marks and Tobena, 1990). Also, fears of
attention and interest from others, but there is no ancestral threats don’t diminish as rapidly in the
supposition that depression as such is adaptive. absence of reinforcement as fears of modern-day
Borderline personality disorder, pathological threats. Evidence like this suggests that common troub-
mourning, and some factitious illnesses can also be ling phobias – such as phobias of snakes, spiders,
understood as miscarried attachment behaviors animals, darkness, and high spaces (American Psychi-
(Wenegrat, 1990a). For example, borderline personal- atric Association, 1994) – reflect evolved mental
ity disorder is characterized by clinging, dependent modules that promote acquisition of fears advantageous
behavior, intolerance of rejection, anxiety, depression, to human ancestors.
poorly controlled aggression, and self-mutilation or Nesse (2001) compared evolved anxiety modules to
injury – such as cutting or burning oneself – in human-made smoke detectors. As an occasional false
response to stress. Nonhuman primates deprived of alarm is better than failure to sound an alarm in the
maternal care show behavioral signs of depression event of a fire, smoke detectors are set to go off at a
and increased aggression and fearfulness. When anx- very low threshold. An evolved anxiety module that
ious, they bite and hit themselves. Studies of border- served to protect from a dire threat might likewise be
line personality disorder patients reveal a very high tuned to sound an occasional false alarm. Individuals
incidence of early abuse or neglect (Paris et al., 1994). whose experience or genes equipped them with slightly
Ethological models may cast light on salient aspects more sensitive innate anxiety modules would be
of serious mental disorders, but they do not account plagued by repeated false alarms, to their detriment.
for all of their signs and symptoms. Schizophrenics, for The cerebral modularity of linguistic functions has
instance, hear voices of people arguing; a model of been known since the nineteenth century. Psycholinguis-
schizophrenia as a failure of group social strategies tic studies support the view that humans have innate
cannot account for this or many other such symptoms. syntactical language processors. According to Timothy
Crow, human vulnerability to psychotic disorders is a
by-product of the modular organization of language
THE INNATE-MODULE PARADIGM (Crow, 1995, 1997; 2002, 2007). Green and Phillips
(2004) cite evidence that specialized neural networks –
Evolved behavior patterns depend on innate perceptual, comprising an evolved social threat detector – rapidly
cognitive, emotional, and motivational processes. For process signs of potential aggression from others. Clinical
example, human males seek exclusive sexual access paranoia might result from excessive activity of this
to fertile women (Trivers, 1985). To do so, they must evolved mental module, which causes ambiguous stimuli
recognize signs of female fertility; experience sexual to be perceived as threatening. Schizophrenics with
attraction to women in general and to fertile women in persecutory delusions have structural and functional
particular; be able to understand their immediate social abnormalities in some of the neural systems described
milieu – including social alliances, sexual rules, and by Green and Phillips.
mores, and styles and manners of courtship; and feel High and low moods reflect changes in activity in
emotions promoting stable, exclusive relationships, such specialized neural circuits (Morgane et al., 2005), which
as affection and jealousy. Insofar as the human brain can be conceptualized as mood modules. Several authors
have analyzed potential adaptive functions served by the social deficits seen in autistic disorders. Among the
normal moods (or normally functioning modules) to findings cited by Baron-Cohen, autistic children fail
shed light on mood disorders (Nesse, 2000; Sloman and to demonstrate joint-attention behaviors: they do not
Gilbert, 2000; Nettle, 2004; Dickinson and Eva, 2006; monitor or follow an adult’s gaze, nor do they point to
Freed and Mann, 2007). To give just one example, objects or show objects to adults as a way of directing
Nesse (2000) argued that normal moods serve to insure attention. To engage in such behaviors, children must
productive effort allocations. In unpropitious circum- surmise an adult’s attentional focus. They fail “false
stances, when goals and desires cannot be fulfilled, belief” tests. A typical false belief test involves seeing
mood is normally lower. At such times, pessimism one person, say Sally, put a marble in one place, and
and low motivation serve to conserve resources that later, while Sally is away, seeing Anne move the object
would otherwise be wasted. In propitious circumstances, elsewhere. When asked where Sally thinks the object is
mood is normally higher (see Tiger, 1979). Optimism located, very young normal children point to where
and increased energy ensure that strong efforts are Anne placed it. Around the age of three or four years,
made to utilize opportunities. Nesse’s view explains the however, they correctly point to where Sally had put it
key role of low expectations in depressive disorders before leaving. They understand Sally’s viewpoint, and
(Overmier, 2002). that Sally has a false belief. Unlike normal children, or
The innate-module paradigm has been applied to mentally handicapped children without autistic fea-
autism, a severe disorder appearing in early childhood tures, autistic children fail such tests at much later ages.
or even infancy (American Psychiatric Association, In the early 1990s, a research group in Genoa study-
1994; Tidmarsh and Volkmar, 2003). Autism – like ing macaques discovered so-called mirror neurons in a
schizophrenia – occurs in milder forms; hence psych- part of the frontal lobe corresponding to Broca’s area in
iatrists now refer to autistic spectrum disorders. human beings (di Pellegrino et al., 1992). Mirror
Severely disturbed children avoid physical closeness, neurons fire just before animals perform specific motor
fail to make eye contact or respond to emotional ges- acts – grasping an object, for example – and also when
tures, and ignore their parents’ voices. They lack inter- they see the same acts performed by others. Such
est in other children or in normal childhood games, neurons seem to encode the concept of the act, whether
such as hide-and-seek. They show stereotyped bodily in self or other. Related neurons in the temporal sulcus
movements, such as clapping, rocking, or swaying, and even encode for intentions (Jellema et al., 2002). For
are fascinated by repetitious motions, such as of fans example, such a neuron might fire when another animal
or pendulums. Older children may become obsessed is observed trying to open a cylinder, regardless of the
with collections or interests, such as bottle-caps or method – twisting the top or pulling it, or whether the
baseball statistics, to the exclusion of other activities act is completed or not.
and interests. Autistic children resist change and prefer Although the evidence is indirect, a system of mirror
unvarying routines. New restaurants, stores, or routes neurons appears to exist in humans (Keysers and
may meet with strong objections. Language skills are Gazzola, 2006). For example, functional brain scans
limited. Higher functioning patients, with the mildest show that human brain regions corresponding to those
forms of autism, generally become independent adults where mirror neurons have been found in monkeys show
with deficits in social skills, but most affected children similar activations in preparation for motor acts and
have a poor prognosis. When it was first described, while observing the same acts. Transcranial magnetic
autism was thought to be extremely rare, but more stimulation (TMS) is a procedure for stimulating regions
recent estimates show that its incidence is about 1 in of cerebral cortex with changing magnetic fields adm-
1000 children. Another 5 in 1000 may have spectrum inistered through the scalp. During TMS, observing a
disorders closely related to autism. While there is a motor act triggers corresponding peripheral nerve activ-
known genetic component to the disorder, environ- ity: A subject who sees someone grasping may show
mental factors may also play causal roles. increased activity in nerves to his own hand.
A critical step in anticipating and altering other Mirror neurons – and neurons encoding intentions,
people’s behavior is to correctly infer their mental state – rather than just actions – encode simple theories of mind.
that is, their beliefs, moods, and desires – from their In an animal study cited above, for instance, neuronal
current and past behavior (Dennett, 1987). Since modern firing signified an inference that an act was intended to
concepts of behavioral evolution suggest that the human open a cylinder – regardless of the method used (twisting
brain was shaped by social necessities, such inferences or pulling) or the actual outcome. Hence, mirror neuron
could depend on evolved neural structures specialized for systems may play key roles in social cognition, including
that purpose. There might be mental modules adapted to theory of mind (Keysers and Gazzola, 2006).
forming accurate theories of others’ minds. The same techniques that reveal mirror neuron
Barron-Cohen (1995) and others suggested that a systems in healthy humans reveal deficits in autistic
deficit in a “theory of mind module” can account for children (Fecteau et al., 2006). For example, with TMS,
558 Brant Wenegrat
they fail to show peripheral nervous activation while gyrus, the frontal cortex, the nucleus accumbens, and
viewing others’ actions (Théoret et al., 2005). Mirror related regions are known to mediate reward and
neuron deficits might disable a theory of mind module pleasure sensations (Baler and Volkow, 2006). In a
in autistics, or the deficit might be elsewhere and drug-free environment, these ancient pathways
reflected in mirror neurons. In any event, if these find- promote adaptive reward-seeking behaviors. However,
ings hold up in future research, they will bolster the modern-day societies expose people to drugs that affect
theory-of-mind hypothesis of autism. neurotransmitters – especially dopamine, glutamate,
Like ethological models, innate-module models may and endogenous opioids – or neurotransmitter recep-
fail to account for critical signs and symptoms of complex tors employed in these pleasure pathways, in effect
mental disorders. Buller (2005), for instance, argued that hijacking the pathways to promote drug-seeking
Baron-Cohen’s treatment of autism ignores serious def- behavior (Lüscher and Ungless, 2006). For example,
icits unrelated to theory-of-mind. Also, some of these cocaine and amphetamine congeners (e.g., amphet-
models may be criticized on the ground that essential amine, methamphetamine, Ecstasy) act to release
mental capacities – even those dependent on localized dopamine from nerve terminals, increasing the
brain circuits – may not be adaptations in a technical amount of dopamine in synapses, and opiates (e.g.,
sense (see Buller, 2005). For example, specific brain morphine and heroin) stimulate receptors that are
regions are needed to read and write. Furthermore, we otherwise only responsive to endogenous opioids
can identify children with highly specific deficits in (endorphins and enkephalins). Sedative hypnotics
reading or writing abilities. Yet, reading or writing (alcohol, barbiturates, benzodiazepines) subject to
“modules” cannot be adaptations, in the sense that they abuse alter the balance between excitatory (mostly
evolved because of advantages accruing from written glutamatergic) and inhibitory (mostly gabaergic) neu-
language. Instead, reading and writing are epiphenom- rotransmission and also stimulate dopamine and
enal skills enabled by brain regions serving more primi- opioid release. In drug addicts, neural pathways that
tive language and visual functions. In the absence might have promoted fitness promote self-destructive
of definite evidence that capacities are adaptations, behaviors that lower inclusive fitness. Heroin addicts,
modular models of illness – however instructive they for example, neglect or abuse their children while
may be – are social-deficit models dressed up in Darwin- ruining their own health. Mothers addicted to
ian garb. cocaine – which has especially powerful effects on
pleasure pathways – may let their children die in order
to stay high.
THE MISMATCH PARADIGM Unlike other drugs of abuse, alcohol was present in
the ancestral environment. Ripe, fermenting fruit is
The mismatch paradigm starts with the fact that human especially rich in calories and nutrients and can be
behavior evolved before the dawn of agriculture, some localized by the odor of alcohol it emits. In frugivores
8000–10 000 years ago, and that too little time has since (fruit eaters) – including nonhuman primates and early
elapsed for large-scale evolutionary changes to have hominids – preference for the smell and taste of ethanol
occurred. If this is true, human behavior evolved in the may be adaptive, since ethanol is linked with nutritional
setting of small hunter-gatherer groups composed of rewards (Dudley, 2000, 2002, 2004). Opportunistic,
close kin moving about in small ranges. Such groups fruit-induced drunkenness has been observed in several
may have resembled extant hunter-gatherer tribes frugivorous species; most famously, elephants.
which have been studied intensively by modern-day Human fermentation of fruits and grains appeared
anthropologists. in Mesopotamia 6000 years ago. Alcohol distillation, to
Modern society is a far cry from the small hunter- produce more potent beverages, was discovered in
gatherer band. Unlike hunter-gatherers, people in seventh-century China and spread to Central Asia, the
modern cities are exposed every day to strangers with Middle East, and later Europe. For the first time, a pref-
whom they have little in common, may live far from kin, erence for the smell and taste of ethanol could lead to
play ambiguous or conflicting roles in multiple social overconsumption. With alcohol freely available, genetic
groups (such as at home, at work, or in their place of differences that were previously fitness-neutral began to
worship), and lack clear authority figures or a sense of moderate the risk of becoming addicted. Research, for
their social placement. If human behavior is adapted to instance, shows that genetic differences in enzymes
life in small groups, then some mental disorders in the involved in degrading alcohol correlate with ethnic and
DSM-IV might result from our living in settings to which racial differences in alcoholism risk, though not with
we are ill adapted: a mismatch, in other words, between other health indices (Mulligan et al., 2003). According to
our current setting and our evolved psychology. this model, alcoholism belongs with obesity and diabetes:
The mismatch paradigm has been applied to disorders fueled by preferences that evolved in conditions
drug abuse. Neural pathways in the anterior cingulate of scarcity, operating now in conditions of oversupply.
The mismatch paradigm may explain societal differ- than those who have not been exposed. This is how
ences in the outcome of schizophrenia. Schizophrenics epidemiologists established that cigarette smoking
living in traditional rural societies are more likely to causes lung cancer and heart disease, and that asbestos
marry and reproduce, to contribute to child-rearing, exposure produces certain malignant tumors. Cur-
and to avoid isolation than schizophrenics living in rently, mismatch models suffer from lack of definite
modern urban societies (Sartorius et al., 1996). As evidence that people in modern societies are actually
discussed above, individuals with schizophrenia spec- mentally worse off than people who live in societies
trum disorders don’t feel part of larger-than-family more akin to ancestral groups. As noted above, a tenta-
social groups as healthy people do, nor do they conform tive case can be made for increased risk of psychosis in
to the consensual worldviews associated with such urban societies, but much more data is needed before
groups. They are loners with odd ideas. Large complex even tentative statements can be made regarding mood
societies with competing and often incoherent world- and anxiety disorders.
views may render schizophrenia-promoting genes much
more dysfunctional than they were in the environment
in which human beings evolved. In a related vein, com- THE PSYCHOTHERAPY PARADIGM
plex urban environments – in contrast to rural ones –
may exacerbate or even cause psychotic disorders, espe- Even with modern medicines, psychotherapy is an
cially in individuals with strong genetic risks (Peen and essential component in the treatment of most mental
Dekker, 2004). disorders (see, for example, Fava et al., 2005;
Two mismatch models attribute anorexia nervosa to Rosenbaum et al., 2006). There are many different
the novel power of media acting on evolved psychological types and schools of psychotherapy, but all of them
processes. In a well-nourished society, slenderness is a aim to change feelings, beliefs, and relationship styles
sign of female youthfulness and hence fertility (Singh, in a healthy direction.
1993). In such a society, same-sex competitive urges A therapist has to decide which of his or her patient’s
cause women to value slimness. Mass media present feelings, beliefs, and relationship styles lead to distress in
them with images of extremely thin high-status women, life, how best to talk about them, and how they can be
such as models and actresses, which they try to emulate. changed. Explicitly or not, such decisions are theory-
The result is self-starvation (Abed, 1998). Alternatively, driven. For example, if a patient whose mother just died
some of the psychological and behavioral traits of seems upset but denies it, a therapist might suggest that
patients with anorexia nervosa – such as their restlessness they’re not acknowledging how their mother’s death has
and subjectively increased energy and their denial of affected him. The suggestion is based on theories of
thinness – may be evolved responses to weight loss that parent–child relationships, loss and normal grief, emo-
helped ancestral humans flee from local famines. In the tional control, and self-deception. Although different
modern world, mass media disseminates unrealistic schools of therapy produce equivalent outcomes, therap-
standards of feminine thinness, girls diet to meet ists who are most aware of the theories that guide their
them, and adaptations to famine are set into motion decisions appear to be most effective in helping patients
(Guisinger, 2003). change (Wampold, 2001). Therapists who cannot articu-
Humans evolved in social groups composed of long- late their reasons for interventions are less likely to help
term familiars. Modern humans, by contrast, may spend most patients.
days surrounded by strangers with whom they can’t Although current therapies are certainly benefi-
communicate. Emigrants or people living or working cial, the conceptual frameworks used by modern-day
abroad are more likely than other people to develop psychotherapists share limitations or weaknesses
paranoid delusions (Allodi, 1982; Kendler, 1982). In such (see, for example, Fancher, 1995). If therapists were
cases, returning home may be curative. Exposure to armed with a more robust conceptual framework,
strangers may also contribute to social anxiety disorder. could they offer more effective help to patients? The
Many patients with social anxiety, for example, are psychotherapy paradigm asks if modern concepts of
limited by anxiety when speaking in front of groups behavioral evolution can help therapists better iden-
(American Psychiatric Association, 1994). If students, tify feelings, beliefs, events, and relationship styles
they cannot take courses which involve giving presenta- relevant to illness and to mental health and to better
tions. If working, they cannot take jobs or accept promo- understand these in particular patients. It asks if these
tions requiring public speaking. Humans in ancestral concepts can offer a robust theoretical framework for
groups would seldom if ever have needed to speak to informing the kinds of decisions psychotherapists
groups of people who weren’t long-term familiars. make.
In testing whether environmental factors cause On the face of it, the answer is likely to be positive.
disease, the first step is usually to see whether individ- Patients in psychotherapy present with feelings and
uals exposed to such factors have higher rates of illness thoughts, and with relationship problems, directly
560 Brant Wenegrat
related to issues addressed in the overall framework of To give a simple example, the ethological attachment
behavioral evolution: among many others, attachment model of depression implies that therapists should
and separation, parent–child conflict and manipulation, pay special attention to patients’ concerns about lost
conflict with siblings and children, conflicts with other relationships. Adaptationist and ethological social rank
kin, regulation of sexual appetites, same-sex and other- models direct attention to patients’ concerns about social
sex conflicts, resource competition, status competition, status. But the therapeutic enterprise is over 100 years
membership in social groups or ostracism from them, old now, and much has already been learned. Therapists
social reputation, reciprocity obligations and moralistic already know that depressed patients ruminate about
aggression, control of aggression and fear of other lost or threatened relationships and/or their social status,
peoples’ behavior, and self- and other-deception. All of and that talking about these issues is vital to their
these have been treated from a Darwinian viewpoint. recovery. In fact, the plausibility of the attachment
In fact, the Darwinian framework is singular in models and the social rank models rests in large part on
explicitly tackling the range of issues encountered by clinical knowledge gleaned by psychotherapists.
psychotherapists.
Adaptationist, mismatch, and ethological models
cited in previous sections may guide therapy of specific SUMMARY
disorders (Glantz and Pearce, 1989; Sloman and Gilbert,
2000; Stevens and Price, 2000a). However, evolutionary Psychiatric disorders are common, occur in all societies,
models of normal behavior may prove to be more and have fitness consequences. Concepts from behav-
valuable in relation to psychotherapy than models of ioral evolution – so successful in accounting for human
illness per se. For example, evolutionary concepts of behavior generally – may shed light on their symptoms,
normal behavior have been applied in relation to clas- causes, and possible treatments.
sical Freudian theory (see, for example, Slavin, 1985; Most work in the field of evolutionary psychiatry
Badcock, 1986; Slavin and Kriegman, 1988, 1992), to has relied on one of five paradigms. The adaptationist
the Jungian notion of archetypes (see, for example, paradigm aims to view mental disorders, their milder
Wenegrat, 1990b; Stevens, 2002), and to some aspects variations, or illness-related traits as behavioral adapta-
of object-relations theory, a branch of psychoanalysis tions that confer or have conferred inclusive fitness
(see Wenegrat, 1990a). Evolutionary treatments of benefits. The best-known adaptationist models are of
normal behavior can also shed light on aspects of schizotypal oddity and depressive episodes, but there
psychotherapy generally, such as mental suggestion also adaptationist models of several other disorders,
(Wenegrat, 2001) and unconsciousness, self-deception such as anorexia nervosa. As we have seen, the evidence
and mental inconsistency (see, for example, Trivers, is weak that any mental disorder or a milder variant is
1985; Kurzban and Aktipis, 2007). an adaptation, in the technical sense, but research on
Findings in social psychology and social cognition reproductive fitness of patients and relatives and its
will prove essential to the psychotherapy paradigm. correlation with illness-related traits – exemplified by a
In many cases, these findings flesh out more abstract study conducted by Nettle and Clegg (2006) – may lead to
concepts from Behavioral Evolution. For example, future progress. Future research could be strengthened
social cognitive research has uncovered mental processes by using life-history data to estimate inclusive fitness,
that produce co-ordinated behavior in larger-than-family which is a broader measure of Darwinian fitness than
groups (reviewed in Wenegrat, 2001). This research and reproductive success (see, for example, Madan, 2002).
the related evolutionary ideas turn out to be highly Whether adaptationist models of mental illness are
relevant to the process of psychotherapy. really needed at all – that is, whether persistence of genes
Of course, evolutionary concepts cannot be used in promoting mental illness really implies some benefits –
therapy except in relation to cultural factors and differ- and whether such models are focused on the right kinds
ences. Evolved behavioral patterns take on particular of benefits are two major open questions.
forms, depending on the culture in which they are The ethological paradigm asks if a mental disorder
expressed. Some cultures, for example, favor paternal can be described economically in relation to elements
investment; other cultures don’t (Kurland, 1979). The of the normal behavioral repertoire observed in all
same paternal behavior – care or neglect – has a different societies. As we have seen, mental disorders can be
meaning depending on whether the culture is of one type characterized as miscarriages of attachment behaviors
or the other. However, the same is true for other theoret- and group-related behaviors. However, ethological
ical frameworks psychotherapists now use: none can be models generally don’t encompass the full complexity
applied in the absence of cultural knowledge. of DSM-IV disorders.
A more serious challenge for psychotherapy The innate-module paradigm asks if mental dis-
models is avoiding triviality or even circular reasoning, orders can be explained in terms of evolved mental
especially when relying on models of mental disorders. modules, as these are hypothesized by Evolutionary
Psychologists. Anxiety, mood, and autistic spectrum flaws in their current conceptions of health, behaviour,
disorders have been analyzed as modular dysfunctions. and therapy processes. If strong concepts and research
Like ethological models, innate-module models often findings from behavioral evolution – along with related
fall short of encompassing the full range of illness ideas from social and cognitive psychology – can be
phenomena, and they are also subject to the concep- broadly disseminated while avoiding the obvious pitfalls,
tual problem vexing evolutionary versions of modular they should be warmly received. To paraphrase Sigmund
theory: the difficulty of proving that given mental cap- Freud, who was writing of dream analysis, the psycho-
acities are technically adaptations. therapy paradigm provides a royal road through which
The mismatch paradigm tries to explain disorders in Darwinian concepts can enter the minds of clinicians.
terms of potential mismatches between our current
environment and our evolved psychology. This viewpoint
is most convincingly applied to drug addiction and to DISCUSSION POINTS
alcoholism. It may also shed light on some little-noticed
epidemiological features of mental disorders, such as 1. Compare and contrast adaptationist and mismatch
cultural differences in the outcome of schizophrenia models of anorexia nervosa (AN). Identify some life
and the high incidence of paranoia in immigrants. As events for which these models predict different
discussed above, cross-cultural incidence data will be effects on the course of patients with AN. For
essential in proving that features of modern society example, what would these models predict for a
cause any mental disorder. mother with AN as she approaches menopause?
Finally, the psychotherapy paradigm asks if modern Identify social conditions which these models pre-
concepts of behavioral evolution can help therapists dict would affect prevalence rates. Do online
understand feelings, beliefs, and relationship styles research to see if some of these predictions have been
relevant to illness and to mental health. It asks if these studied. (Suggestion: start by searching Medline at
concepts can offer an overarching framework for the www.ncbi.nlm.nih.gov/pubmed.)
types of decisions psychotherapists make. The psycho- 2. Argue for and against the following proposition:
therapy enterprise is over 100 years old now, and much “Evolutionary psychiatry is bedeviled by confusion
is already discovered. To be successful, the psychother- between extreme mental states and their normal
apy paradigm will have to do more than tell therapists counterparts.” In arguing this point, consider each
what therapists already know, while avoiding circular of the major disorders described in this chapter
reasoning. and each of the separate paradigms. Which para-
It seems likely that all five paradigms will figure in digm(s) are best equipped to deal with normal
the future of evolutionary psychiatry. Adaptationist states? Which paradigms are best equipped to deal
models may explain some disorders, while ethological, with extreme states?
innate-module, or mismatch models explain others. 3. The risk of schizophrenia is increased in individ-
Several paradigms may apply to a single disorder: uals whose mothers had influenza in the early
For example, creativity may explain the persistence of second trimester. Likewise, the risk of schizophre-
certain risk genes in the families of schizophrenics, while nia in offspring of schizophrenics appears to be
dysfunction of social cognition accounts for who actually increased by complications at birth. Which of the
falls ill. Cultural variation in the outcome of schizophre- evolutionary models of schizophrenia described in
nia may be due to factors explained by mismatch this chapter can most readily accommodate these
models. Adaptationist models might account for mild facts? How could such findings be reconciled with
depression, while ethological or innate-module models other models?
better describe severe depression. The triggers for mild 4. Schizophrenics and major depressives have high
depression and the causes of ethological or modular lifetime risks of suicide. How might you reconcile
dysfunctions that occur in severe depression might both adaptationist models of these disorders with these
be analyzed in terms of mismatch models. high suicide risks? Under what conditions might
Above all the others, the psychotherapy paradigm suicide have positive effects on inclusive fitness?
probably holds the key to the future of evolutionary With these conditions in mind, why should schizo-
psychiatry. Although it can utilize work from each of phrenics and major depressives be more likely to
the other paradigms, the psychotherapy paradigm kill themselves than anyone else?
doesn’t require robust models of mental disorders. As 5. Describe several novel predictions derived from
we have seen, for the most part such models are lacking. adaptationist models of mental disorders. Do
Existing evolutionary accounts of normal behavior are online research using databases like Medline to
equally – if not more – relevant to psychotherapy than find existing data pertaining to your predictions.
models of mental disorders narrowly conceived. Further- If you can’t find such data, briefly outline studies to
more, many practicing therapists are keenly aware of test your predictions.
562 Brant Wenegrat
6. Describe several novel predictions derived from Bowlby, J. (1969). Attachment and Loss, vol. 1. New York:
mismatch models of mental disorders. Do online Basic Books.
research using databases like Medline to find Bowlby, J. (1973). Attachment and Loss, vol. 2. New York:
existing data pertaining to your predictions. If Basic Books.
you can’t find such data, briefly outline studies to Bowlby, J. (1980). Attachment and Loss, vol. 3. New York:
Basic Books.
test your predictions that could be performed in a
Bulik, C. M., Sullivan, P. F., Tozzi, F., et al. (2006). Prevalence,
single country.
heritability, and prospective risk factors for anorexia ner-
7. Psychotherapy often focuses on patients’ responses
vosa. Archives of General Psychiatry, 63(3), 305–312.
to disturbing events. From the point of view of Buller, D. J. (2005). Adapting Minds: Evolutionary Psychology
behavioral evolution, describe some common events and the Persistent Quest for Human Nature. Cambridge,
that some or all individuals might find especially MA: MIT Press.
disturbing. Patients sometimes misconstrue minor Burns, J. K. (2006). Psychosis: a costly by-product of social
events as disturbing ones. Keeping in mind Nesse’s brain evolution in Homo Sapiens. Progress in Neuro-
“false alarm” hypothesis of anxiety disorders, which Psychopharmacology and Biological Psychiatry, 30(5), 797–814.
individuals might be especially likely to perceive the Chagnon, N. A. (1979). Mate competition, favoring close kin,
events you’ve described when they’ve not really and village fissioning among the Yänomämo indians.
occurred? Evolutionary Biology and Human Social Behavior: an
Anthropological Perspective, N. A. Chagnon and W. Irons
(eds). North Scituate, MA: Duxbury Press, pp. 86–131.
Cosmides, L. and Tooby, J. (1997). The modular nature of
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33 Industrial
Evolution
Pollutants and Human
Lawrence M. Schell
INTRODUCTION: THE ANTHROPOLOGICAL humans? And, given that the study of pollutants is not
STUDY OF INDUSTRIAL POLLUTANTS traditional in anthropology, what is the right way to
determine if industrial pollutants have any effects on
Human experience with industrial pollutants is very human biology, evolution, and health? An important
recent and very brief relative to the span of our species’ and related question is, how do anthropologists deter-
evolution. Marked increases in pollution exposure mine successful adaptation, what are the appropriate
began in the mid 1700s with the industrial revolution. measures?
It seems paradoxical that Homo sapiens evolved in This chapter will address these questions but the
response to features of decidedly nonindustrialized conclusions are provisional. The research necessary to
environments but is now largely an urban species living address these questions is still developing across a
in industrialized societies. Are we somehow prepared broad range of disciplines. Typically, reviews of
by our evolutionary history to deal with industrializa- research on pollutants are organized to describe the
tion, or is this an adaptive challenge confronting effects of one pollutant at a time. In contrast, this
modern Homo sapiens? review is organized by endpoints that relate to chal-
This large question is dissected into more scien- lenges to reproduction: human growth and aging, mor-
tifically manageable ones that evolutionary human bidity and mortality which are areas anthropologists
biologists can use to structure research. For example, have studied to understand human evolution and bio-
using demographic measures of species success (Gage, logic variation (Stinson et al., 2000). Due to space limi-
2005), Homo sapiens appears to be flourishing. This tations this is not a comprehensive review of all
conclusion is based on comparisons of populations’ pollutants, or of all effects of any one pollutant. An
mortality profiles, over space and in different historical effort is made to include contrary studies in each case
periods. Using other measures of adaptation however, to emphasize methodological issues that are raised by
such as patterns of growth and development or mor- the diversity in results. The review is intended to intro-
bidity patterns, the adjustment may appear far less duce the subject including the inherent methodological
than complete. Although industrialization produces difficulties that may produce variety in the results.
economic benefits and related health benefits, it also Unfortunately, the review cannot include a description
produces pollutants that are detrimental to biological of global warming and its impact on human evolution
systems particularly among the socioeconomically dis- although global warming is clearly related to industrial
advantaged. Should we consider all the impacts pollution and may have a tremendous impact on
together in a summary measure of success such as life our species.
span, or should we “unpack” the urban environment by An important consideration when considering pol-
determining the specific constituents of urban environ- lution’s effects on human evolution is how much of an
ments, and considering the effects of each constituent impact do pollutants make? This is a difficult question
on specific outcomes (Schell and Ulijaszek, 1999)? This to answer for several reasons. Most research on pollu-
latter approach is taken here. By analyzing the ques- tants concerns disease outcomes rather than fertility or
tion in terms of effects of specific industrial pollutants, other effects of import to evolution (changes in gene
we may be able to see the direct effects of these elem- frequencies in a population). In large populations such
ents, remembering that the relationship between as those in industrialized societies where pollution is
industrialization and health is dynamic and could generally greatest, fertility is low and influenced
change (Schell and Ulijaszek, 1999). greatly by social factors. Natural selection in response
The questions are these: Are there features of to pollution and modern stressors in such populations
industrialization that pose biological challenges to has not been studied and probably cannot be because
566
Industrial Pollutants and Human Evolution 567
of the limitations of modern methods. However, evolu- biologists have left biological typology behind and
tion may be affected without natural selection operat- may now leave environmental typology behind as
ing as the two are not synonymous, and evidence for well. A second reason is the effect of offsetting impacts.
nonadaptive genetic changes, such as mutations, in Industrial pollutants may have detrimental effects that
response to pollutants are evidence of evolutionary pose challenges to adaptation yet at the same time the
change too. delivery of health care may be more intense in indus-
trialized areas. The two opposing forces can balance
one another producing a net effect of zero in a general
HOW WILL WE EVER KNOW? METHODS, health measure. However, this does not mean that the
METHODS, METHODS pollutants are innocuous. The third and final reason is
that the aggregate approach does not recognize the
Knowing the answer to the questions of effects of many effect of social arrangements, by which I mean all the
environmental features, including pollution, depends terms that are used today to indicate that power rela-
on the suitability of methods. Generally we observe tions in societies structure resources, exposures and
only statistical relationships between pollutants and risks that produce biological differences along lines of
health effects because we would not knowingly create social difference (Schell, 1998). Health disparities
an experiment by exposing persons to possibly injuri- (minority, “racial” [sic], or ethnic disparity) is the term
ous pollutants. With observational studies there are used in public health to describe this. Thus, large
five elements that should be present (usually requiring aggregates may seem healthy but the analysis of health
more than one study) to determine if the pollutant by social gradients within these larger aggregates may
actually causes the biological effect, and these are reveal the true biological challenges.
known as Hill’s Criteria of causation. The criteria A better approach is to measure the amount of
most often emphasized are: (1) a dose–response rela- exposure to a particular pollutant and compare that
tionship between putative cause and effect; (2) a bio- to specific effect of interest to human biologists (fertil-
logically plausible relationship; (3) replication of ity, menstrual cycle characteristics, sperm counts, pre-
results; (4) a temporal sequence (cause precedes reproductive mortality, growth, development, etc.).
effect); (5) a strong relationship; and (6) consistency Human biologists have excellent methods for measur-
across tests of the relationship. When all six conditions ing effects in physiological systems, but measuring the
are met we are much more certain that a relationship environmental factor is often not as rigorous. This is an
observed between a pollutant and a health effect has a example of unbalanced precision. Comparisons of
causal basis. urban and rural populations, the environmental typ-
Sometimes there is a reason to relax at least one of ology referred to just above, involves not measuring
these criteria. For example, some biologically implaus- environmental features as they are assumed to be the
ible relationships between a pollutant and a health same in each type of environment. This approach pre-
effect have turned out to be true, and in pursing the vents observation of effects of the specific features of
implausible we learn about new biological processes. each. Measuring those features should produce more
In this vein, sometimes a straight dose–response rela- accurate descriptions of their effects, and yield more
tionship does not fit the data and a U- or J-shaped accurate and reliable information.
relationship is evident. Today the matter of hormetic
effects, that is a reversal in the direction or strength of
a dose–response relationship that occurs at very low WHAT ARE INDUSTRIAL POLLUTANTS?
levels of exposure, is under close investigation (Cala-
brese, 2005). Pollution is usually defined as an unwanted material
The old standby approach of comparing industrial- or energy that is considered a threat to well-being. Pollu-
ized and nonindustrialized populations is no longer tants are produced by industrial processes, but many
used to discern effects of specific pollutants for several pollutants, carbon dioxide (CO2), methane, dust, etc.,
good reasons (Schell and Denham, 2003). Firstly, are produced by natural processes as well (Waldbott,
industrialized places vary amongst themselves as do 1978). For this reason alone humans may have physio-
nonindustrialized ones. Further, they do so across sev- logical mechanisms to deal with exposure to some pollu-
eral dimensions and continuously. To classify settle- tants. Some of the best information on pollutants is
ments into just two categories is a form of typology, available through US government websites (for example
and typology steamrollers over variation. A typological http://www.atsdr.cdc.gov/toxpro2.html).
approach to understand the impact of industrialization Persistent organic pollutants (POPs) are a group of
ignores the diversity inherent in such populations, compounds that are toxic, are resistant to breakdown
and thus it cannot use that diversity to understand in the environment (indeed many were created to
the different impacts of industrialization. Human have this property for industrial or agricultural
568 Lawrence M. Schell
TABLE 33.1. Persistent organic pollutants.

despite widespread reductions in environmental lead
The US Environmental Protection Agency’s “Dirty achieved over the past 25 years.
Dozen.” Humans are exposed to lead and POPs chiefly
through the diet, although airborne and dermal routes
Industrial
Pollutant Pesticide chemical By-product of exposure may contribute to some extent also.
Humans consume POPs in commercially available
Aldrin X foods, fish caught locally in contaminated waterways,
Chlordane X as well as through packaging. Nonoccupational lead
Dichlorodipheny- X exposure occurs largely through ingestion especially
ltrichloroethane
by placing nonfood items in the mouth, which is very
(DDT)
common among toddlers. Respiration of lead particles
Dieldrin
makes a far smaller contribution to the intake. Expos-
Endrin
ure to industrial pollutants is widespread. The US
Heltachlor
Centers for Disease Control and Prevention (2005)
Hexachlorobenze X X X
reported that evidence of tobacco smoke, lead, mer-
Mirex X
cury, and phthalates are detected in nearly the entire
Toxaphene X US population and nearly 150 chemicals were detected
Polychlorinated X X in some portion of the US population.
biphenyls (PCBs)
Air pollution is a heterogeneous mixture including
Polychlorinated X
oxides of nitrogen (NOx), oxides of sulfur (SOx), carbon
dibenzo-p-dioxin
monoxide (CO), ozone (O3), and particulate matter
Polychlorinated X
dibenzo-p-furans (PM). Particulate matter is usually classified by par-
ticle size. Particulate matter is not only a pulmonary
irritant but also is a vehicle to bring specific com-
pounds into the lung and then the bloodstream where
it can produce systemic effects.
applications). Generally POPs are lipophilic and there- Noise is the only pollutant included in this review
fore are present in dietary fats and are stored in that is not a material but a form of energy (radiation
adipose tissue. As a result of this biologic process, and light are others). Noise is defined as unwanted
POPs typically increase in tissue concentration up the sound, and is measured in terms of duration, fre-
food chain in a process termed biomagnification quency, and volume (decibels). Noise produces both
(Table 33.1; http://www.epa.gov/oppfead1/international/ auditory and nonauditory effects, the former related
pops.htm). Thus, animals near the top of the food chain, more to the nerve damage produced by the energy
piscivores and carnivores, can have substantial concen- content, and the latter by its ability to create annoy-
trations of POPs because in a lifetime they consume ance, stimulate the autonomic nervous system and to
many animals that have consumed other animals that produce stress (Kryter, 1985). Thus, although noise is
have consumed small quantities of POPs. Notable POPs measured as energy, its nonauditory effects are pro-
are polychlorinated biphenyls (PCBs) and dioxins which duced by stress.
have similar structures (Figure 33.1). It is impossible to include here detailed descriptions
Phthalates are compounds used widely in con- of the routes of exposure to these pollutants, although
sumer products primarily to soften plastic items such such maps provide ample interesting evidence of the
as shower curtains, garden hoses, food containers, but social input to pollutant exposure of interest to anthro-
also can be present in floor tiles, furniture upholstery, pologists (Schell and Czerwinski, 1998). Likewise,
shoes, hairspray, and other products used in daily life details of pollutant measurement methods would
(Yang et al., 2006). They are found in polyvinylchlor- require substantial additional space, although they per-
ide, which is widely used and familiar to us as plastic tain to the quality of research discussed. Readers are
plumbing and vinyl siding. Phthalates are also found in referred to the many excellent reviews and texts on this
plastics used in medical tubing, and are found in air, subject (National Research Council, 1999).
water, and food (Duty et al., 2003).
Lead is a base metal that is completely unnecessary
for human health. Lead dust is more concentrated POLLUTANTS AND PRENATAL GROWTH:
alongside roadways as a result of deposits from vehicle OPPORTUNITY FOR FETAL PROGRAMMING
exhaust, and in, on, and around older homes painted AND EFFECTS
with lead-based paint. Depressed, older, inner-city
neighborhoods with both features have populations Alterations in the pattern of prenatal growth are most
with higher lead levels relative to other populations commonly discerned as changes in birthweight, length
(a) (b)
3 2 2′ 3′ Cl O Cl
Clx Cly
O O
1 1′
4 4′ Cl Cl
O
PCDD
5 6 6′ 5′ 2,3,7,8 - tetrachlorodibenzo-p-dioxin
(c)
3′ 3
HO O CH2 CH C OH
5′ 5 NH2 O
3,5,3′,5′,-Tetraiodothyronine (thyroxine, T4)
HO O CH2 CH C OH
NH2 O
3,5,3′,-Triiodothyronine (T3)
(d)
OH
I IO
33.1. Polychlorinated biphenyl (a), dioxin (b), thyroxine (c), and estradiol (d), showing similarities in
structure that are thought to underlie some of the hormonal effects of the toxicants. The numbered
positions on each ring of the polychlorinated biphenyl may be substituted with a chlorine. Depending
on the location and number of substitutions, the molecule will vary in persistence and toxicological
properties. Unchlorinated molecules can resemble dioxin and dibenzofurans which are considered
highly toxic.
of gestation, and the occurrence of congenital malfor- unsuccessful changes as programming but consider
mations. Alterations in prenatal growth signify adverse these changes as the result of constraint. These would
circumstances for growth and development and pos- be changes in fetal growth induced by the environment
sibly health generally (Schell, 1997). Alterations in that produce malformations or other clearly detrimen-
growth patterns also suggest the action of fetal pro- tal effects. Distinguishing between altered fetal growth
gramming with significant effects occurring far later that is a part of fetal programming from altered fetal
in life (Kuzawa and Pike, 2005; Newbold et al., 2006). growth that is only detrimental, is difficult on theoret-
Fetal programming refers to alterations in fetal physi- ical grounds (Ellison and Jasienska, 2007).
ology through epigenetic processes, wrought by infor- The classic work on programming concerns the
mation transferred from mother to fetus. Programming influence of nutrition on adult health and disease. How-
can result in altered patterns of postnatal growth and ever, a recent review of research on pollutants and
functioning, and much later affect adult health. Pro- reproduction emphasized the role of pollutants in modi-
gramming usually refers to changes that are adaptive fying the epigenome (the biochemical reactions that
in the short term in that they are thought to allow fetal influence and constitute gene expression) (Woodruff
survival or anticipate conditions in postnatal life, but et al., 2008). As more studies on pollutants and gene
may involve changes with a cost, and could be detrimen- expression find links of exposure to later adult health,
tal to health in later life. As such they involve a classic pollutants should be considered another influence on
trade-off between resources devoted to promote growth fetal programming.
versus those devoted to promote reproduction. Gener- Pollutants can alter prenatal growth and or pro-
ally most writers on programming do not include duce effects pertinent to reproduction later in life.
Although such effects have not been considered cognitive development even at rather low levels of
programming as just described, they have all the out- blood lead, although contrary studies can be found also
ward signs of it except the production of benefit (for review see Andrews et al., 1994). The case of lead is
at some point in the life span. The classic case of instructive because the size of the reduction in birth-
chemical modification of long-term development is weight or head circumference may be small, but the
diethylstilbestrol (DES) (Newbold, 2004). This is a syn- size of the affected population is enormous.
thetic sex hormone with estrogenic effects prescribed Evidence for an effect of POPs on prenatal growth
to many pregnant women in the mid twentieth century is extensive but not consistent (see Schell 1991, 1999
to prevent miscarriage but was ineffective. However, it for reviews, and for some evidence of the complexity of
did promote the development of vaginal cancer in the analysis also see Berkowitz et al., 1996; Longnecker
young adult women who were in utero while their et al., 2001; Eskenazi et al., 2003). The strongest evi-
mothers were taking the drug. Thus, we know that dence for an effect comes from studies of the offspring
exogenous hormones can influence the developing of Japanese and Taiwanese mothers who consumed
reproductive system and produces significant late- rice oil contaminated with a mixture of POPs including
occurring effects including changes in behavior and dibenzofurans and PCBs. The contamination caused a
adult-onset disease. Hormonally active agents in the disease called Yusho in Japan and Yu-cheng in Taiwan.
environment are of great concern (National Research Offspring in utero at the time the rice oil was con-
Council, 1999). sumed were smaller at birth in both cases (Yamaguchi
There have been several reviews of studies on air et al., 1971), and offspring exposed in utero after con-
pollution and prenatal growth (Schell and Hills, 2004; sumption ended were smaller also probably from POPs
Lacasana et al., 2005; Sram et al., 2005) and in addition stored in mother’s adipose tissue from the earlier
to the main finding of reduced prenatal growth, it is exposure (Yen et al., 1989). Studies of birth size in
apparent that the strength of biological effects varies relation to fish consumption (Dar et al., 1992), a
by pollutant. There are mixed findings for effects of common route of POP exposure, are complicated by
nitrogen dioxide (NO2), carbon monoxide (CO), and the nutrients in fish that promote prenatal growth
sulfur dioxide (SO2). At this time the strongest evi- (Jacobson, 2004).
dence is for an effect of particulate matter including Noise is a consistent by-product of many industrial
increased frequency of low birthweight and prematur- processes and transportation in industrialized soci-
ity (Xu et al., 1995; Bobak, 2000; Lee et al., 2003; Leem eties. Changes in mean birthweight and the frequency
et al., 2006), small for gestation age (Parker et al., of low birthweight may be influenced by noise pollu-
2005), and intrauterine growth retardation (Dejmek tion because noise is capable of producing a stress
et al., 1999) as well as to reductions in mean birth- response during pregnancy (Welch and Welch, 1970;
weight (Chen et al., 2002; Yang et al., 2003; Gouveia Committee on Environmental Health of the American
et al., 2004; Parker et al., 2005). The validity of air Academy of Pediatrics, 1997). Many studies of popula-
pollution’s role is supported by the worldwide distributions living near airports find that noise stress from
tion of studies in this literature: e.g., Canada, China, airplane takeoffs and landings is associated with
Czech Republic, Korea, Taiwan (Xu et al., 1995; Bobak reduced prenatal growth (for review, see Schell and
and Leon, 1999; Bobak, 2000; Liu et al., 2003; Lee et al., Denham (2003). Studies conducted in Japan have ana-
2003; Yang et al., 2003). When results are replicated in lyzed large numbers of births and found a clear dose–
different societies it suggests that the statistical associ- response relationship between noise levels and the fre-
ations are not produced by bias from uncontrolled quency of small newborns (Ando and Hattori, 1973) as
variables especially socially mediated ones. Some well as temporal associations between the introduction
uncontrolled variables exist in most observational of loud jet aircraft and the frequency of small new-
studies, but the same configuration of socially medi- borns (Ando, 1988). Repeated associations of the same
ated variables is less likely to occur when many differ- direction and magnitude, a temporal association and a
ent societies are studied. dose–response curve all support the theory that noise
The effect of lead on prenatal growth is now well stress affects prenatal growth. No single study is defini-
established and the problem of impaired cognitive tive by itself, but when the entire body of work is
development has been included in US Government considered in conjunction with laboratory and field
publications on the risks of lead exposure (Centers for studies of short-term physiological responses to airport
Disease Control and Prevention, 1991). Studies con- noise (Evans et al., 2001) most of the criteria for a
ducted in a variety of settings, including those where causal inference are met. There are, however, studies
lead exposure does not covary closely with poverty as it that have not found effects. Some have studied women
has in the United States (Bornschein et al., 1987; exposed to lower levels of noise than is found around
Bellinger et al., 1991a, 1991b; Gonzalez-Cossio et al., airports or noise that is expected and therefore not
1997; Schell and Stark, 1999) show that lead impairs necessarily very stressful (Wu et al., 1996).
What is true for all studies of environmental influ- controlled for socioeconomic factors and body size
ences is that findings pertain to a specific range of statistically.
exposures, and the effects reported in any single Delay in reaching menarche in relation to blood
study depend on the range of exposure present. Some lead level was observed also among Akwesasne
variation in results across studies of different expos- Mohawk adolescents. Also, PCBs were associated with
ures and social circumstances is therefore expected a significantly earlier age at menarche (Denham et al.,
and evident. 2005). In this study, not all PCBs were associated with
changes in age at menarche, and the effect was found
with a group of estrogenic congeners identified as such
ENDOCRINE SYSTEM EFFECTS: GROWTH, through laboratory studies. Polybrominated biphenyls
MATURATION, AND MENARCHE (PBBs) have been associated with earlier age at menar-
che and attainment of pubic hair stages in breast-fed
Many POPs are known to alter the development of girls (Blanck et al., 2002). However, Flemish adolescents
some parameter of the endocrine system that suggests experienced delayed sexual maturation in relation to
effects may develop later in life (Brouwer et al., 1999; polychlorinated aromatic hydrocarbons (Staessen
Stein et al., 2002). Growth, sexual maturation, men- et al., 2001; Den Hond et al., 2002). Furthermore, age
strual cycle characteristics, sperm quality by numerous at menarche among girls in Seveso, Italy who had been
measures, fertility, and fecundability have been stud- exposed to dioxin from an industrial explosion, was not
ied in one or more populations, usually retrospectively, altered (Warner et al., 2004). Interestingly, the authors
following known exposure. Nevertheless, there is noted that most effects of dioxin seen in laboratory
ample evidence for effects on these parameters. studies were from prenatal exposure, whereas the
Effects of some pollutants on postnatal physical sample of Seveso girls had had postnatal exposure only.
growth have been reviewed (Schell and Knutson, These results illustrate the variation in effects that
2002). Blood lead clearly influences postnatal growth can be found in studies of many groups of pollutants.
and development even at moderate to low levels Here there is a variety of chemical substances involved
(Ignasiak et al., 2006). Also, POPs can affect growth, in uncontrolled exposures at possibly different ages and
the strongest evidence coming from studies of children at different doses. As these results are based on obser-
exposed to rice oil contaminated with a variety of POPs vational studies of humans, the cause and effect rela-
including dibenzofurans and PCBs (Rogan et al., 1988). tionship cannot be inferred. Support for a true causal
Studies of other samples are supportive of 1,1-dichloro- relationship is derived from experimental studies in
2,2-bis(p-chlorophenyl)ethylene (DDE)-related effects which laboratory animals were dosed with a toxicant
(Gladen et al., 2000; Longnecker et al., 2000) and PCBs and experienced delayed maturation (for example, with
may play a role as well (Blanck et al., 2002; Gallo et al., lead, McGivern et al., 1991; Corpas et al., 2002; Dearth
2002). Air pollution is related to poorer physical growth et al., 2002), suggesting that the associations in humans
in many studies (reviewed in Schell and Hills, 2004); for do not occur by chance and are not caused by some
particularly good recent studies see Jedrychowski et al. other unmeasured factor (Goldman et al., 2000).
(1999) and Jedrychowski (2000).
Sexual maturation holds special interest as altera-
tions in age at menarche relate to the length of the ENDOCRINE SYSTEM EFFECTS: FEMALE
reproductive span and may affect fertility. Alterations REPRODUCTIVE FUNCTIONING
in age at menarche also signal significant effects on the
system of endocrine and central nervous system (CNS) Some of the earliest studies of PCBs found substan-
control over maturation and other related endpoints tially reduced fertility and increased newborn mortal-
such as ovulation, fertilization, implantation, and ity among rhesus macaques (Allen et al., 1979). Animal
reproduction generally. Age at menarche is also related models continue to be important in studying repro-
to adult-onset diseases. ductive effects as PCBs have been related to alterations
In humans populations, lead and persistent organic of the menstrual cycle in nonhuman primates (Willes
pollutants have been associated with changes in age at et al., 1980), and studies in other model species (rats,
menarche. Analyses of data representing the US popu- mice, and mink) are confirmatory (http://www.atsdr.
lation showed that the level of lead in the blood at the cdc.gov/DT/pcb007.html).
time of interview was associated with delayed menar- Strong evidence of effects among humans comes
che among girls 8–18 years of age (Selevan et al., 2003; from studies following the Yu-cheng accident. Women
Wu et al., 2003). The delays varied from one to six who had consumed rice oil that had been contamin-
months. Also attainment of Tanner breast and pubic ated with a combination of POPs (dioxin, dibenzofur-
hair stages was associated with very small increases of ans and PCBs) had significantly more abnormal
blood lead levels from 1 to 3 g/dL. The investigators menstrual bleeding (Yu et al., 2000). Girls who had
been exposed in utero had higher rates of irregular answered well by studies of human populations
menstrual cycles, and serum estradiol and follicle- because of the normal variation in sperm quality, the
stimulating hormone (FSH) were higher too (Yang large variety of pollutants that might be tested for
et al., 2005). influence, and the presence of other influences that
Premenarchael girls in Seveso, Italy exposed to may go unmeasured. Many studies focus on one or
dioxin had longer menstrual cycles after they reached two pollutants leaving questions concerning the roles
menarche compared to women who were postme- of other pollutants unanswered, and there are a
narcheal when exposed (Eskenazi et al., 2002). How- number of measures of quality being used. The result
ever, women exposed to PCBs through consumption of is a large body of literature on humans that is uneven,
contaminated fish from the US Great Lakes and containing many reports of relationships and other
women exposed through the consumption of Baltic reports of their absence. Studies of laboratory animals
fish, had cycles of reduced length (Mendola et al., and in vitro studies provide the most control and weigh
1997; Axmon et al., 2004). heavily in favor of the ability of many pollutants to
Carefully constructed studies have shown that detrimentally influence sperm or testicular develop-
PCBs are associated with reduced female fecundability ment in some way (Andric et al., 2000a, 2000b; Gold-
(Buck et al., 2000) and longer time to conception man et al., 2000; Faroon et al., 2001; Gray et al., 2001;
(Courval et al., 1999). Higher miscarriage rates have Corpas et al., 2002; Veeramachaneni, 2008; Woodruff
been reported also (Gerhard et al., 1998), and in the et al., 2008).
Yu-cheng cohort, more stillbirths and preadolescent A fairly consistent finding is that some measures of
deaths of offspring (Yu et al., 2000). Though PCBs were sperm quality are affected by air pollution levels. In a
not related to menstrual cycle length or other cycle careful study of young men from Teplice, Czech
parameters, dichlorodiphenyltrichloroethane (DDT) Republic, which is highly industrialized, clinical meas-
level (measured as DDE) was significantly associated ures of sperm quality (number, motility, frequency of
with shorter cycles, including the luteal phase length malformations) did not vary systematically in relation
alone (Windham et al., 2005). to episodes of air pollution. However, the sperm chro-
Although POPs are involved in all these studies, matin structure assay showed that the percentage of
they can differ considerably in their effects, and in sperm with DNA fragmentation was significantly ele-
the laboratory have been shown to produce estrogenic vated in relation to such episodes (Rubes et al., 2005).
or anti-estrogenic, androgenic or anti-androgenic Such fragmentation may cause increased rates of male
effects. Some are known to act through different recep- mediated reproductive effects including infertility and
tors. The timing of exposure is likely to produce differ- miscarriage. Comparing Teplice men with men from
ent effects as well. Seemingly contradictory results an unindustrialized area, however, showed more
(delayed or accelerated sexual maturation) may be abnormal chromatin, a lower proportion of motile
consistent with exposure to different types or combin- sperm, sperm with normal morphology, and normal
ations of POPs, and especially to the timing of exposure sperm head shape among the Teplice men, although
in the context of sexual differentiation and develop- mean and median sperm concentration and count did
ment prenatal and possibly other critical periods. not differ (Selevan et al., 2000).
Evidence for effects of different PCB congeners on
measures of sperm quality is mixed. Follow-up of
EFFECTS ON SPERM AND THE MALE Yu-cheng boys exposed in utero show that they had
REPRODUCTIVE SYSTEM DEVELOPMENT increased abnormal sperm morphology, reduced
motility, and reduced hamster oocyte penetration cap-
This is a controversial topic (Toppari et al., 1996; acity compared to controls (Guo et al., 2000) as well as
Giwercman and Bonde, 1998; Chia, 2000). Numerous reduced penile length at 11–14 years of age (Guo et al.,
studies have related an apparent decline in some meas- 1993). Studies of males chronically exposed to lower
ures of sperm quality (number, motility, frequency of levels of POPs have produced less clear results. Sperm
sperm deformations) to an increase in exposure to chromatin integrity was related to levels of PCB (CB-
pollutants while others have not (Carlsen et al., 1992; 153) in a consistent dose–response relationship among
Fisch et al., 1996; also see Chapter 21 of this volume). European men but not in Inuit men from Greenland,
Some of the controversial elements of this body work and no relationships with DDE levels were detected
include whether there has in fact been a decline in (Spano et al., 2005). Significantly less sperm motility
sperm quality or a change in sampling the population was found in men with relatively high levels of marker
(for example, including more older men) that mimics PCBs than in the less exposed (Rignell-Hydbom et al.,
such an effect, and whether there is any relation 2004) and no differences were related to levels of DDE.
between concurrent pollutant exposure and sperm Studies comparing fishermen on the east coast of
quality (Comhaire et al., 2007). The question is not Sweden, where PCB and other POP contamination
levels are high, to those on the west coast, where they weight, was inversely related to levels of blood
are lower, have found negative associations of this phthalates (Swan et al., 2005) suggesting that some
exposure with sperm motility, sperm chromatin integ- phthalates are anti-androgenic. Boys with short dis-
rity, and Y:X chromosome ratio but not with sperm tances for body weight also had higher frequency of
concentration or semen volume; couple fertility did not undescended testicles and scrotal sacs characterized as
differ (Axmon et al., 2008). Other studies have reported small or indistinct from surrounding tissues.
no relationship between PCB exposure and fertility and The relationship of blood lead levels to measures of
sperm counts (Emmett et al., 1988a, 1988b; Buck et al., male fertility, particularly sperm quality or function,
1997). It may be that metabolites are more potent has been well established through many studies
than the parent compounds as sperm count and motil- of humans and in experimental work with animals.
ity have been associated with PCB metabolite levels Generally, among workers at a lead–zinc smelter,
(Dallinga et al., 2002). sperm count and concentration were related to the
A set of recent studies based on a sample of drawn concentration of blood lead especially among those
from men using the andrology laboratory at Massachu- men with a specific genotype of d-aminolevulinic acid
setts General Hospital used a novel measure, the dehydratase (Alexander et al., 1998). Analysis of the
Comet assay that measures DNA integrity, showed that fertility potential of sperm in conjunction with in vitro
sperm DNA damage was associated with specific urin- fertilization efforts found that seminal plasma lead
ary phthalate metabolites after statistic adjustment for levels were related to decreased human sperm function
appropriate covariates (Duty et al., 2003; Hauser et al., (Benoff et al., 2003), and decreased success with in
2007). An additional study examined the effect of a vitro fertilization (IVF). These results on sperm func-
combination of certain PCBs and phthalates and found tion agree to a great extent with findings from studies
that the combination was strongly related to “below of laboratory animals (as reviewed in Benoff et al.,
reference value sperm motility” (Hauser et al., 2005). 2003) and with findings from studies of fertility and
The authors used standard World Health Organization lead levels. Importantly, the findings from studies of
measures of sperm motility, and the measured levels of male partners of IVF patients are relevant to the gen-
phthalate metabolites in this sample were typical of eral population because the lead levels are similar to
levels in US men, generally suggesting that the findings reference values and are below levels associated with
may apply widely. Other studies have found elevated decreased sperm function and fertility through occu-
serum estradiol levels and decreased sperm motility in pational exposure (Lancranjan et al., 1975).
relation to exposure to pesticides and solvents (Oliva
et al., 2001).
As a conclusion to the different results from studies DIABETES AND OBESITY
of humans, consider the study by Kuriyama and Cha-
houd (2004) who found that low doses in utero of one Diabetes and obesity are associated with reduced fer-
PCB (#118) produced smaller testes, epididymides and tility in both men and women. Factors that contribute
larger seminal vesicles, decreased sperm and sperm- to increased obesity and diabetes may indirectly influ-
atid numbers, and impaired daily sperm production ence fitness. In recent years independent studies from
in adult male rats. Whereas other studies have shown different parts of the world, the United States, Bel-
that large doses produce increased sperm production gium, and Sweden, have demonstrated that levels of
and testis weight (Cooke et al., 1996; Kim, 2001). dioxins and PCBs are related to diabetes and obesity.
Researchers have postulated that effects at different Using data from the US National Health Examin-
doses of endocrine mimics may produce very contrary ation Survey, diabetes prevalence was strongly and
effects (nonlinear, U-shaped, etc.), especially so with positively associated with lipid-adjusted serum concen-
regard to endocrine mimics (Calabrese and Baldwin, trations of the six POPs found in 80% or more of the
2003; Kuriyama and Chahoud, 2004). The study of sample. The analysis included adjustment for appro-
low dose effects from POPs has raised serious ques- priate control variables including age, sex, race, body
tions about the nature of dose–response generally, and mass index (BMI), waist circumference, poverty level,
the monotonic dose–response relationship, once con- etc. A strong dose–response relationship was evident
sidered a hallmark of causal relationship between in the data. The risk of diabetes increased steadily
exposure and an effect, may not be that hallmark in with increasing POP level and was several-fold greater
every instance. in groups above the 75th percentile of toxicant
Ano-genital distance, a measure usually much level compared to those below the 25th percentile
greater in males than females, is a frequently used (Lee et al., 2006).
measure of sexual differentiation in toxicological stud- In a Belgian sample, levels of POPs were between
ies of rodent sexual development (Sharpe, 2001). 62% and 39% higher in diabetic patients compared to
Young boys’ ano-genital distance, corrected for body controls, a highly significant difference before and
after statistical adjustment for appropriate covariates Genotoxicity

(Fierens et al., 2003). The risk of diabetes was signifi-
The genotoxicity of air pollution was discovered
cantly greater in the top tercile of toxicant level; risk
through investigations of the relationship between air
ratios varied between 5.1 and 13.3 depending on the
pollution and lung cancer (Pope et al., 2002). Several
compound or group of compounds, In a Swedish
studies have demonstrated that air pollution, particu-
sample there were positive though weaker relation-
larly exposure to polycyclic aromatic hydrocarbons
ships between diabetes risk and chlorobiphenyl and
(PAHs), is associated with increases in measures of
DDE levels (Rylander et al., 2005).
genotoxicity, specifically changes in carcinogen-DNA
adducts and carcinogen-protein adducts using in vitro
methods. These are mutations in somatic cells but the
AIR POLLUTION: A SPECIAL CASE ability of air pollution to affect genes in human germ
cells is a matter pertaining to human evolution and
Anthropological concern with the evolutionary signifi- therefore of importance to anthropologists.
cance of pollutants requires focusing on influences Air pollution can contribute to chromosomal
on fitness. Evidence of an association between air abnormalities. Chromosomal abnormality frequency
pollution and standard measures of fitness is not a was calculated for 60 African-American and Domin-
subject of study in public health where most of the ican mother–infant pairs living in low income areas
research is concentrated. Most studies of the effects of New York (Bocskay et al., 2005). Airborne PAH level
of air pollution on mortality focus on adults and par- measured by air monitoring was significantly and posi-
ticularly the elderly where effects are thought to be tively associated with stable chromosomal aberrations
greater and of greater significance to public health. in cord blood though not with unstable ones which are
Nevertheless, in the air pollution literature there is less significant as a cancer risk.
work on some indirect influences on fitness such as The genotoxicity of PAHs is supported by compari-
sperm quality and effects on the age of attainment of sons of levels of airborne PAHs and genotoxicity of
sexual maturation, both of which influence the length particles (greater than 10 mm) collected in Antwerp,
of the reproductive span. However, evidence is now from an industrial site, and a rural site (Brits et al.,
accumulating that indicates that some types of air pol- 2004). The most damaging particles came from the
lution have more direct effects that pertain to human urban area and were highest in PAH concentration.
evolution. Genetic damage could result from airborne particles
or from compounds adhered to them because particles
more easily enter the distal lung tissue where com-
Prereproductive mortality
pounds are absorbed into the bloodstream and can be
Studies of air pollution have a long history and carried to the liver. There they may be metabolized into
there is arguably more information on its effects chemicals more damaging to DNA and then carried to
than any other pollutant. The link between air pollu- the spermatogonial stem cells in the testes (Samet
tion and adult mortality is soundly established by et al., 2004). Studies of human lung cell cultures also
population-based studies (Dockery et al., 1993; Pope, show dose-dependent increases in genotoxicity in
1999). Anthropological concern with the evolutionary terms of DNA breaks (Dybdahl et al., 2004; Karlsson
significance of pollutants requires greater attention to et al., 2004).
influences on fitness especially to prereproductive Studies with animal models allow for manipulation
mortality. of exposures and stronger inferences regarding causal
The first well-documented episode of pollution connections. The most informative studies to date
related mortality was the London smog of 1950 formed demonstrated that heritable mutations in mammals
by particulates and SO2 from home heating fires Adult may be caused by particulate air pollution, and that
mortality was increased and infant mortality was the primary contributor is the PAH compounds.
increased significantly as well, although this point Laboratory mice 6–8 weeks old housed downwind
was not fully appreciated against the higher death rates from steel mills for 20 weeks had 1.5–2.0 times the
among the elderly. Recently studies of infant deaths in number of heritable mutations compared to an unex-
Mexico City have pointed to the role of small particular posed group, and primarily inherited through the
matter (PM2.5, e.g., particulates smaller than 2.5 mm in paternal line (Somers et al., 2002). In a follow-up study,
diameter) (Loomis et al., 1999). An increase of 10 units mice caged in an industrial environment breathing
in the level of particulates less than 2.5 mm in diameter unfiltered air had significantly elevated mutation rates
(PM2.5) was linked to a 4–7% excess mortality in compared to mice kept in rural areas with unfiltered or
infants (excluding accidents and other sources of mice breathing HEPA-filtered air in either rural or
mortality clearly unrelated to air pollution). industrial environments (Somers et al., 2004). As
HEPA filtration reduced the expanded simple tandem metabolized, the dose or exposure, and when in devel-
repeat (ESTR) mutation rates at the industrial site, the opment it occurs. They do not all produce the same
airborne agents that were filtered were responsible for constellation of effects. Some groups of pollutants do
the elevated rate, and these were most likely PAHs. alter parameters that pertain to reproduction and fit-
Taken together, these studies demonstrate that ness. Germ-cell mutations, reduced fertility in males
some component of air pollution, probably PAHs, is and females, changes in menstrual cycle characteris-
able to produce heritable mutations in mammals. The tics and measures of male potency, as well as in the
impact of these mutations in germ cells on human pattern or timing of sexual reproduction have been
mortality, morbidity, and evolution has yet to be linked to one or more pollutants in several different
investigated. studies of humans. Research ethics do not permit ran-
domized control trials of humans and pollutants,
which is appropriate but makes it virtually impossible
GENETIC VARIATION IN SUSCEPTIBILITY to formally establish cause and effect. Yet, there is
TO INDUSTRIAL POLLUTANTS plentiful supporting evidence from laboratory studies
of the same pollutants among appropriate animal
In the simplest terms, for natural selection to occur models that is substantial and cannot be dismissed.
genetic variation in a trait must be linked causally to Certainly there are unknown factors that create vari-
variation in the contribution of offspring number to ability in results. Further research will identify these
the following generation. This may be due to differen- and in so doing will increase knowledge of normal and
tial fertility, mortality, or by some more indirect path. disturbed reproduction.
If genetic susceptibility to the effects of industrial pol- Since Silent Spring was published (Carson 1962),
lutants exists, and these effects may affect fertility or scientists have known something of the power of pesti-
mortality before the end of the reproductive span, then cides to alter reproduction. More recently, Our Stolen
selection may occur for variations conferring protec- Future (Colborn et al. 1996) has reawakened concern
tion against such effects. about the long-term effects of pesticides and pollutants
Much of the evidence for genetic variation in sus- generally on human reproduction and health. The US’s
ceptibility to pollutants is drawn from studies of PAHs National Research Council (1999) report, Hormonally
and aromatic amines. Both are generated by combus- Active Agents in the Environment, has substantiated
tion, the first from fossil fuels and the second from many concerns about chemicals and human reproduc-
cigarette smoke and other sources. The genes most tion, and even a cursory examination of government
often found related to variation in response to carcino- websites dealing with toxicants finds many reports of
gens are the metabolic genes (P450), glutathione S- effects on reproduction. Differences in reproduction is
transferase (GST) and the N-acetyltransferase (NAT) not by itself evidence of evolution, but it is a required
(Perera, 1997). Common genetic polymorphisms in element. Understanding how genetic variation associ-
P450s and NAT2 have an impact on cancer suscepti- ates with reproductive effects is the next step in under-
bility. Increased lung cancer risk upon exposure to a standing how pollution may affect human evolutionary
carcinogen, especially at low dose, is associated with trajectories.
one or more of the CYP1A1 polymorphisms.
DNA repair varies tremendously. The activity of
two DNA repair enzymes, O6-alkyldeoxyguanine-DNA
alkyl-transferase and uracil DNA glucosylase, differs DISCUSSION POINTS
by over 100-fold within humans (Perera, 1997), which
is linked to increased cancer risk. Genetic variation in 1. Which pollutant seems most likely to influence
receptors involved in toxicokinetics of carcinogens human evolution?
also impact risk of cancer. An important receptor for 2. What evidence is there that pollutants really are
effects of many aromatic hydrocarbons such as dioxin bad for human populations, and what standard is
and some PCBs, as well as PAHs, is the arylhydrocar- applied to decide this?
bon (Ah) receptor. Individuals with this high-affinity 3. Is it possible that humans are adapted to any of the
binding receptor upregulate CYP1A1, CYP1A2, and pollutants discussed, and if so, how could this have
other genes. happened?
4. What evidence is required to prove that a pollutant
influences human evolution and is it possible to
SUMMARY AND CONCLUSION collect that information in less than a generation
with methods currently available?
Pollutants exist in a huge variety and their effects 5. Why is it so difficult to know the effects of
depend on their chemical structure, how they are pollutants?
the Czech Republic 1986–8. Occupational and Environ-

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34 Acculturation and Health
Thomas W. McDade and Colleen H. Nyberg
INTRODUCTION populations represent a Rousseauian vision of humans

living in harmony with their environment, with incur-
We currently live in an era of rapid globalization, with sions leading to losses of autonomy and disruptions in a
few societies beyond its reach. In 1950, 30% of the delicate homeostasis that impair health (Wirsing,
world’s population lived in urban areas; today the pro- 1985). For others, health improves when cultural and
portion of urban residents is nearly 50%, and will economic trends provide reliable access to nutritional
exceed 60% by 2030 (United Nations, 2001). Expansions and health care resources (Dennett and Connell, 1988;
in international trade, market economies, and formal Gage, 2005). Still others recognize both the challenges
systems of education provide opportunities for some and opportunities of change, and explicitly consider the
and social inequality for many, while a global mass multiple, and potentially conflicting, paths through
media fuels new consumer desires and expectations which cultural and economic factors may shape health
(Ger and Belk, 1996; Navarro, 1999). Populations that (Berry et al., 1986; McElroy, 1990; Godoy et al., 2005c;
were once relatively isolated – geographically, linguis- Steffen et al., 2006).
tically, culturally – are becoming increasingly exposed Many terms have been used to describe the processes
to, or interfacing with, novel environments and life- of change that affect health, including “acculturation,”
styles that may differ considerably from their own. “Westernization,” “modernization,” and “market inte-
What implications do these processes have for human gration.” While these terms reflect significant differences
biology and health? For our understanding of processes in emphasis, they all share a common interest in linking
related to human adaptation? individual well-being to surrounding social, cultural,
These questions have been hotly debated by anthro- economic, and political dynamics. “Acculturation” fore-
pologists, epidemiologists, and economists for over half grounds changes in local culture resulting from regular
a century, and simple answers are not forthcoming. interaction between two or more autonomous cultural
Most research focuses on the health impact of recent systems (Social Science Research Council Summer
transitions related to globalization, but it is important Seminar, 1954). “Westernization” and “modernization”
to recognize that human biology has been shaped by typically focus on the development of a cash economy,
dynamic relationships with cultural, economic, and secularized government, systems of formal education,
broader ecological factors since the Neolithic Revolu- and urban residential units (Levy, 1966; Spindler,
tion. For example, rises in infectious disease associated 1984). “Market integration” focuses more specifically
with shifts from hunting and gathering to sedentization on the emergence of market-based systems of exchange,
and agricultural intensification beginning about 10 000 and the degree of participation in, and dependence on,
years ago can be considered the first epidemiologic markets to meet subsistence needs (Godoy, 2001).
transition (Barrett et al., 1998). Links between cul- Obviously, these are overlapping, closely related
tural/economic transitions and health are fundamental processes of change, and in this review we use the more
to human evolutionary biology since morbidity and general term “cultural and economic transitions” to
mortality are important correlates of reproductive fit- encapsulate all of them. After introducing key concepts
ness, and because cultural/economic factors define, in that serve as a foundation for research in this area, we
large part, the environments to which humans adapt. review the state of current knowledge regarding the
Field-based research on cultural/economic changes health impact of cultural and economic transitions in
and health has provided an opportunity to explore populations around the world. We discuss the mechan-
mechanisms of human adaptation, and to consider the isms through which these transitions affect human biol-
local consequences of broader cultural and economic ogy and health, and highlight the models that have been
processes. For some scholars, isolated indigenous used to reveal these associations.
581
582 Thomas W. McDade and Colleen H. Nyberg
DEVELOPMENT OF KEY CONCEPTS

Culture, adaptation, and health
History
Although frequently invoked as a causal factor in shaping
Despite elegant work by Boas (1911) with immigrant human behavior, biology, and health, culture is rarely
populations demonstrating biological plasticity in operationalized and a consensus definition remains
response to environmental change, prevailing concep- elusive. For most purposes, culture can be defined as
tualizations of human populations as genetically socially transmitted systems of shared knowledge,
fixed and bounded entities dominated into the 1940s beliefs, values, and/or behaviors that vary systematically
(Little, 1982; Johnston and Little, 2000). The predom- across recognizable social groups (Tylor, 1924). Culture
inance of such typological thinking left little room for is a primary component of the human adaptive strategy.
serious consideration of cultural factors as determin- For the past 20000 years humans have inhabited a
ants of human biological variation. However, in the wider ecological and geographic range than any other
1950s and 1960s, evidence for adaptive biological respon- vertebrate, and – for better and for worse – over the past
siveness to climatic stressors – cold, heat, altitude – began 10000 years humans have become Earth’s dominant
to accumulate in a wide range of human populations, species due to the emergence of sophisticated techno-
thereby documenting considerable phenotypic plasticity logical and social systems (Alexander, 1991; Boyd and
and setting the stage for an ecological approach to human Richerson, 2005). Culture reduces the costs of learning
biology. and increases the breadth and accuracy of knowledge
With a renewed emphasis on theory and hypothesis accumulated across generations, and it is a necessary
testing, the “new physical anthropology” (Washburn, input for normal cognitive and neurological development
1951) encouraged a series of studies – many as part of (Changeux, 1997; Tomasello, 1999). Culture is thus
the International Biological Programme – on biobeha- often seen as providing solutions to challenges posed to
vioral mechanisms of adaptation to diverse environments reproduction and survival, but it simultaneously creates
around the world (Baker and Weiner, 1966). Climate, new problems in these same domains (Schell, 1997). For
disease, nutrition, and other aspects of the physical example, cultural factors may allocate risks and
ecology were investigated as primary stressors with resources along lines of residence, occupation, and/or
implications for human development and health. From social class. In some situations, inequality in the distribu-
this perspective it was but a small step to acknowledge tion of resources may be so pronounced that reproduc-
cultural factors as key organizers of exposure to, and tion and survival are compromised for significant
buffers against, environmental stressors (Baker et al., numbers of individuals. Thus, culture is both a buffer to
1986; Huss-Ashmore, 2000). adversity and an unequal allocator of risk to health, pro-
These historical developments set the stage for viding adaptive opportunities as well as challenges
culture change and health as a major area of ongoing (Thomas, 1992; Schell, 1997). Lasker (1969) outlined
research in human biology, with the field currently three levels at which organisms adapt to shifting eco-
confronting two significant challenges. The first con- logical circumstances: (1) genetic modifications resulting
cerns the recognition that the majority of research on from natural selection across generations; (2) ontogen-
culture and health relies on relatively simplistic under- etic modifications that emerge over an individual life
standings of culture, and that more sophisticated course; and (3) short-term physiological and behavioral
operational definitions of cultural factors are needed in responses. Recently, Kuzawa (2005) has proposed
future research (McDade, 2002; Dressler, 2005). The “phenotypic inertia” as a fourth level of adaptability,
second concerns the importance of political–economic intermediate in time course between genetic and onto-
factors in structuring exposure to stressors associated genetic changes, which allows for intergenerational
with change, and in constraining ability to respond to transmission of information through nongenetic mech-
those stressors in ways that attenuate their adverse anisms. Humans are unique among animals in the degree
impact on health (Singer, 1996). An emphasis on plasti- to which we rely on behavioral responses and extra-som-
city and the mechanisms through which humans are able atic adaptations to facilitate survival and reproductive
survive in a wide range of environments can divert atten- success, an attribute that provides considerable flexibility
tion from the quality of these environments – many of in response to environmental change.
which are marginal, at best – and runs the risk of natur- Culture is thus a key mechanism of human adapt-
alizing or justifying social inequality. Human biologists ability, but it also constructs in large part the settings
have recognized this risk, and a number of studies have to which humans must adapt. For humans, culture
attempted to consider the local effects of global pro- is the environment. Shifts in the cultural landscape
cesses, the biological costs of adaptation, and the social can therefore be expected to result in phenotypic
and economic relations underlying adaptive capacity changes at multiple levels by acting through genetic,
and stress exposure (Leatherman and Goodman, 1997; intergenerational, ontogenetic, and/or physiological/
Goodman and Leatherman, 1998). behavioral mechanisms.
Acculturation and Health 583
There are a number of cases demonstrating the Developmental inertia is a relatively unexplored mechan-
impact of cultural factors on human genetic diversity ism linking cultural and economic transitions to health,
(Durham, 1991). For example, classic research in West but it is likely to be particularly important for under-
Africa suggests that the intensification of agriculture standing secular trends in growth and chronic disease.
led to changes in the population frequency of alleles Similar developmental mismatches – albeit within a
protective against malaria (Livingstone, 1958). Clearing shorter time frame – have been invoked as mechanisms
wide patches of tropical rainforest provided abundant to explain a wider range of associations between culture
breeding grounds for the mosquito vector, which change and health. Early work on the social origins of
encouraged the transmission of malaria and conferred hypertension, for example, suggested that incongruity
a selective advantage upon resistant individuals. between the cultural environment an individual is social-
Although cultural transitions have left their mark on ized into as a child and the one he or she functions in as
the human genome – particularly in a deep evolutionary an adult, may lead to upregulation of stress pathways and
time frame – it is important to emphasize that contem- poor health (Cassel, 1974). Similarly, individuals who
porary human populations adjust to environmental grow up at high altitude acclimatize by developing larger
changes primarily through nongenetic mechanisms. lung volumes, whereas individuals who migrate to high
This is due to the slow pace of genetic change, as well altitude as adults do not show the same level of functional
as the exceptional degree of phenotypic plasticity that is capacity in hypoxic environments (Frisancho, 1978).
a defining trait of the human species. Behavioral and The vast majority of research on how environments
developmental mechanisms provide more rapid, flexible, affect health focuses on the final mechanism of adap-
and mutable options for adaptive responsiveness such tation: short-term (i.e., nondevelopmental) physio-
that genetic changes come into play only as a “last logical and behavioral responses to challenge. This
resort” (Slobodkin, 1968; Huss-Ashmore, 2000). reflects the importance of phenotypic plasticity to the
Recent interest in the early life origins of adult dis- human adaptive strategy, and is particularly the case
ease (see Chapters 2 and 30 of this volume) has provided for research on culture and health, since most investi-
evidence that “intergenerational inertia” may be an gators are interested in the impact of relatively rapid
important mechanism linking cultural/economic transi- cultural and economic transitions, typically occurring
tions and health. For example, in the Philippines, adoles- within a single generation. This body of research is the
cents have high levels of cholesterol despite low rates of primary focus of this chapter, with numerous
obesity and relatively low intakes of dietary fat, and examples discussed below.
unexpectedly high rates of hypertension at any given It is important to acknowledge that the relationships
level of body mass (Colin Bell, et al. 2002; Kuzawa among environmental stressors, processes of adapta-
et al., 2003). These results – and similar findings from tion, and health are not always straightforward. For
other populations as well as research with animal example, the development of a thrifty phenotype in a
models – suggest that prenatal undernutrition leads to nutritionally marginal environment may well represent
permanent changes in organ structure and physiological an adaptive process, but the consequences for health in
function that lower the energy needs of the individual as a nutrient-rich environment (obesity, chronic disease)
an adult. In teleological terms, the developing organism are hardly positive. Similarly, even though a thrifty
uses the prenatal environment to predict future resource phenotype may be beneficial in a nutritionally marginal
availability such that a “thrifty phenotype” may be an environment compared to a more spendthrift pheno-
adaptive response to an impoverished nutritional type, undernutrition early in life compromises work
ecology. capacity, reproductive performance, cognitive function,
But when calorie-dense foods are readily available and longevity (Martorell, 1989; Pelletier et al., 1995) –
later in life, prenatal undernutrition may make individ- again, outcomes that are clearly suboptimal. For these
uals particularly vulnerable to diseases related to energy reasons, some scholars eschew the term adaptation
surplus, including obesity, cardiovascular disease, and altogether when making reference to human biological
diabetes. Globally, industrial agriculture and commercial responses to social, economic, and cultural contexts,
food production are increasing the availability of concen- particularly when these contexts are impoverished
trated sources of calories (e.g., refined sugar, cooking (Pelto and Pelto, 1989; Frisancho, 1993; Singer, 1996).
oils), and levels of physical activity are dropping Several general hypotheses follow from this discus-
(Popkin, 1994, 2003). Populations experiencing rapid sion of the mechanisms of adaptation that can be used
nutritional and lifestyle changes may be particularly vul- as a guide for research into the impact of cultural and
nerable to the contribution of “developmental mismatch” economic transitions on human biology and health.
to chronic degenerative diseases. Birthweights in India, Firstly, since changes in gene frequency in response
for example, are among the lowest in the world, yet the to shifting selection pressures represent an exceedingly
country is currently experiencing an epidemic of type II slow mechanism of “last resort,” few studies are likely to
diabetes despite low levels of obesity (Yajnik, 2004). find genetic signatures of natural selection in response
to contemporary changes in the cultural and economic features of this literature prior to discussing the path-
environment. This does not deny the importance of gen- ways linking change and health.
etic mechanisms of adaptation in an evolutionary time
frame, nor does it discount the possibility that the
Topical foci
unique evolutionary history of a particular population
may shape its response to contemporary environmental The major emphases of recent studies have been on
changes in significant ways (Snodgrass et al., 2007). outcomes related to child growth, chronic degenerative
Secondly, intergenerational and developmental pro- diseases such as obesity, cardiovascular disease, and
cesses provide a degree of phenotypic plasticity for diabetes, and mental health. Changing patterns of
infants and juveniles that is not available to adults. With infectious disease have also received considerable
fewer mechanisms of adaptation online, adults can be attention, while other health outcomes addressed in
expected to pay a higher biological toll in response to recent studies include violent deaths, and risk behav-
rapid environmental change than they would have paid iors such as substance abuse.
if they confronted the same changes earlier in life. Simi-
larly, conditions experienced early in life – prenatally Child growth
and in infancy – can be expected to have long-term as Measures of growth and nutritional status are sensitive
well as intergenerational implications for health in the indicators of past, present, and future health, and have
context of changing environments. therefore served as key outcomes for research on the
Thirdly, the pace of change should be associated impact of cultural and economic transitions. In part
with its impact on health. Rapid cultural and economic due to the relative ease of anthropometric data collec-
transitions pose more immediate adaptive challenges by tion, studies of child growth have been conducted in a
opening up larger gaps between old and new environ- wide range of populations, with mixed results (Panter-
ments, and by constraining options for phenotypic Brick et al., 1996). In some settings, cash earnings from
adjustments that strive to optimize fitness. Genetic, market activities are used to purchase food and to
intergenerational, and developmental mechanisms of supplement traditional diets, which may improve
adaptation, for example, do not apply in situations of nutritional status and reduce growth stunting (Santos
rapid change, and behavioral responses – particularly and Coimbra, 1991; Stinson, 1983; Norgan, 1995;
those embedded in cultural systems handed down across Reyes et al., 2003; Godoy et al., 2005c; Foster et al.,
generations – may have to overcome considerable inertia 2005). In others, market participation leads to an
before they can serve as effective buffers. Related to this increase in growth stunting through nutritional stress
point, the adverse health impact of environmental or an increase in infectious disease that acts synergistic-
change should be greatest in the short term, and should ally with undernutrition to impair growth (Fitton,
attenuate over time through phenotypic responsiveness 2000). In the Andes, the impaired statural growth of
on multiple levels. many high-altitude populations was revealed to be the
result of poverty and disease, rather than primarily high
altitude stress, underscoring the role that inequalities in
CULTURAL AND ECONOMIC TRANSITIONS access to the benefits of economic development play in
AND HEALTH: WHAT DO WE KNOW? shaping child growth (Leonard, 1995; Leatherman,
1998). While one in four children globally suffer from
In the past 25 years, over 200 peer-reviewed studies have undernutrition (de Onis et al., 2004), in many develop-
been published investigating the impact of cultural and ing nations the prevalence of childhood obesity and
economic transitions on health in diverse populations associated metabolic disorders is growing rapidly
around the world1. Few consistent patterns of association (Gracey, 2003).
emerge from this literature, cautioning against any
attempts to draw sweeping conclusions regarding the Chronic degenerative diseases
impact of cultural and economic change on health in One of the most consistent findings of recent research is
contemporary populations. Here we summarize key the positive association between market integration
and the emergence of chronic degenerative diseases.
1
This estimate is based on searches in electronic databases Increases in adult body weight and the prevalence of
(PubMed, PsychInfo, Google Scholar), as well as anthropo- obesity have been demonstrated in several populations,
logical journals and bibliographies of past publications on the and at differing levels of articulation with market econ-
topic. A variety of search terms were used to capture the most
inclusive sample of articles, including acculturation, Westerniza- omies (Zimmet et al., 1980; Baker et al., 1986; Norgan,
tion, modernization, market integration, urbanization, industrial- 1994; Shephard and Rode, 1996). Similarly, blood pres-
ization, and culture change. Studies were included if they sure is higher for adults in affluent countries and in
contained individual-level health outcomes (i.e., no regional or
national level datasets) and were studies of in situ c hange (i.e., populations that have moved away from subsistence-
not studies of migrants). based economies. Mortality rates from cardiovascular
disease are also elevated (Scotch, 1963; Waldron et al., speculation that the encroachment of Western insti-
1982; Poulter et al., 1990; Dressler and Bindon, 1997; tutions and values, the decline of local communities,
Egusa et al., 2002; Steffan et al., 2006). Often, the “mod- the disintegration of extended family networks, and a
ernization” gradient in high blood pressure is more lack of economic opportunities have contributed to
pronounced in men than in women, although the precise adolescent stress (Kraus and Buffler, 1976; Macpher-
mechanisms underlying this difference remain unclear son and Macpherson, 1987; Rubinstein, 1992;
(Schall, 1995). Accompanying changes in body compos- McDade, 2002). A model of acculturative stress pro-
ition and blood pressure is the emergence of type II posed by Berry and Kim (1998) suggests that degree of
diabetes in a range of populations, including Pacific distress depends largely on whether those acculturat-
Islanders (Prior and Rose, 1966), Australian Aborigines ing wish to maintain their traditional identity, and the
(Norgan, 1994), Pima Indians (Ravussin et al., 1994), and degree to which they want to integrate and interact
among circumpolar peoples (Shephard and Rode, 1996). with those in the new culture (Berry and Kim, 1998).
Although changes in diet and reductions in physical Research on response to colonial stressors among
activity levels are obvious contributors to cardiovascular Inuit youth highlights the role of coping behaviors
and metabolic diseases, psychosocial distress associated in buffering stress-related health outcomes (O’Neil,
with culture change may also be a powerful factor 1986), while several studies in the Samoa Project
(McGarvey and Schendel, 1986; Steffen et al., 2006). have documented physiological responses to the psy-
In addition, mismatch between prenatal nutritional chological and behavioral changes accompanying
environments and those encountered later in life may rapid social and economic transition (McGarvey and
be an important, though relatively unexplored, mechan- Schendel, 1986; Baker et al., 1986; Pearson et al.,
ism leading to the development of chronic disease 1993). Recent research with an Amazonian horticul-
(see Chapter 30 of this volume). turalist population in the early stages of transition
While broad-scale epidemiological surveys indicate suggests that greater participation in the market econ-
that rates of cancer are increasing dramatically through- omy is significantly linked to anger, fear, and sadness
out the developing world, scant data are available directly (Godoy et al., 2005c).
linking this increase to cultural and economic transi- The effects of psychological distress may also
tions. As with cardiovascular and metabolic diseases, manifest through the emergence of excessive alcohol
changes in diet and activity levels are thought to be major consumption and substance abuse. While these
contributors: excessive bodyweight has been recognized behaviors may initially serve as coping mechanisms
by the World Cancer Research Fund as an important risk in response to the experience of acculturative stress,
factor for many malignancies (World Cancer Research the consequences for individual health and commu-
Fund and American Institute for Cancer Research, 2007; nity well-being can be devastating (Berry, 1970; Neff,
Renehan et al., 2008). However, the link between obesity 1993; Dressler et al., 2004). Sporadic episodes of binge
and certain cancers may vary dramatically between sexes drinking are common among communities undergo-
and populations of different geographic origin. ing rapid social and economic transitions, and may be
In addition, the adoption of risky behaviors such as most problematic (Graves, 1967; Singer et al., 1992).
smoking and alcohol abuse have also been hypothesized Cigarette smoking has been documented in many
to contribute. For example, high rates of lung cancer transitioning populations, but precise estimates of
among indigenous Siberian populations have been duration and frequency of smoking are not known.
linked to smoking, while increased rates of reproductive The abuse – rather than controlled social or ritual
carcinomas have been attributed to high rates of sexually use – of marijuana, stimulants, cocaine, depressants,
transmitted diseases and high-risk sexual behavior in tranquilizers, and hallucinogens has also become
Arctic communities (Freitag et al., 1991). China, which more common among many indigenous communities
has the largest global production and consumption of (Shephard and Rode, 1996; Curtis et al., 2005). Alco-
tobacco, experiences over 1 million smoking-related hol and substance abuse have also been implicated in
deaths each year, most the result of lung cancer (Zhang escalating rates of accidents and violent crimes
and Cai, 2003; Jiang et al., 2008). among modernizing populations (Curtis et al., 2005).
Mental health and substance abuse Infectious and parasitic diseases

Several studies have documented increased rates of Infectious disease persists as a major contributor to mor-
depression and suicide, as well as increased levels of bidity and mortality around the world. While historical
physiological indicators of stress, in populations in improvements in standard of living have reduced rates of
transition (Graves and Graves, 1979; Brown, 1981; infectious disease (McKeown, 1976), contemporary asso-
Dressler, 1991; Shephard and Rode, 1996). Epidemics ciations with cultural and economic transitions are
of adolescent suicide among circumpolar popula- mixed. Economic development may facilitate prevention
tions, in Samoa, and in Micronesia have fueled and treatment by providing access to health-care
resources, yet it may also contribute to disease transmis- biological, and health data it compiled (Baker et al.,
sion and severity through degradation of the local ecol- 1986). The project took advantage of the recent emer-
ogy (Walsh et al., 1993; Brinkman, 1994; Santos et al. gence of a “modernization gradient” across the islands
1997). Rapid urbanization may contribute to increases to reveal a general pattern of increasing obesity, hyper-
in population density, erosion of basic infrastructure, tension, adverse lipid profiles, as well as adverse stress
deforestation, and changing subsistence and agricultural hormone profiles in individuals residing in more West-
patterns with direct implications for pathogen exposure ernized areas. Several studies have continued to track
(Armelagos et al., 1996; Garruto et al., 1999). For these trends over time (McGarvey, et al., 1993;
example, in Guyana the conversion of cattle-grazing Keighley et al., 2007), and to explore culture change
fields to a more economically viable cash crop, rice, pro- as a source of adolescent stress (McDade et al., 2000;
vided an ideal breeding ground for mosquitoes. Conse- McDade, 2002).
quently, malaria rates soared (Desowitz, 1976; Brown Similar findings emerged from the Tokelau Island
and Whitaker, 1994). The case of the Aché of Paraguay Study, in which a cohort of central Pacific islanders were
underscores the profound impact of infectious disease on surveyed before migration to New Zealand in 1967 and
immunologically naı̈ve Amerindian populations: two- then followed post-migration for over two decades. The
thirds of the adult population developed tuberculosis health consequences of migration included a shift
within just 20 years of sustained contact with outsiders toward a more carbohydrate- and sugar-laden diet, a
(Hurtado et al., 2003). greater likelihood of developing gout, adverse lipid pro-
Although macroparasites have received less attention files, an increase in the prevalence of type II diabetes,
than other infectious diseases, they may play a major role and a modest increase in blood pressure (Stanhope and
in malnutrition, growth stunting, and comorbidity with Prior, 1980; Prior et al., 1987; Salmond et al., 1989).
other infections (Lawrence et al., 1980). In cases where A similar study in the Solomon Islands revealed more
urbanization is associated with higher parasite loads, modest post-migration changes in blood pressure and
increased infection is often attributed to crowding, poor body composition (Page et al., 1974; Friedlander, 1987).
sanitation, and proximity to animals and fecal material In Papua New Guinea, the relative isolation of the
(Confalonieri et al., 1991; Fitton, 2000). Type of water highlands has provided a baseline for comparison with
source may also be a significant predictor of parasite the more rapidly transitioning settlements in coastal
exposure: in the Philippines, neighborhoods which relied areas, and numerous studies have demonstrated links
on rain water rather than irrigation canals had a higher between economic integration and elevated blood pres-
prevalence of the water-borne parasite schistosomiasis sure, body mass index (BMI), and reduced activity levels
(Payne et al., 2006). In other populations, increased (Jenkins, 1989; Schall, 1995; Yamauchi, et al., 2001;
market integration and education have been linked to a Ulijaszek, 2007). Other studies based in Papua New
reduction of intensity in intestinal parasites, a pattern Guinea have cautioned against the assumption that
observed among the Tsimane’ of the Bolivian Amazon isolated highland populations represent idealized states
(Tanner, 2005). of good health and harmony with the natural environ-
ment: many of these populations have long histories of
contact with outsiders, and rates of undernutrition and
Regional foci
infectious disease are high (Dennett and Connell, 1988).
While research into the health impact of cultural and
economic transitions has been conducted globally, the Arctic
Pacific Islands, Latin America, and the Arctic have Circumpolar populations provide case studies in
served as particularly important testing grounds for mechanisms of adaptation to extreme cold, but arctic
exploring the physiological and psychological correl- research has also served as a major foundation for
ates of lifestyle change. Many of the projects in these exploring the ramifications of acculturation on psy-
areas represent the legacy of human adaptability chological and physical health. The Inuit of northern
research initiated by the International Biological Pro- Canada, for example, are frequently cited as a classic
gramme and the Man and the Biosphere Programme example of how acculturation can provoke mental
(Little et al., 1997). distress and undermine health through risk behaviors
such as smoking and alcoholism (Berry, 1970; Lynge,
Pacific Islands 1976; O’Neil, 1986; Shephard and Rode, 1996). In
Rapid economic development in the Samoan islands addition to increased rates of infectious diseases
occurring post-World War II provided a compelling introduced through contact with outsiders, circumpo-
backdrop for a comprehensive assessment of the lar peoples have experienced soaring rates of chronic
impact of lifestyle changes on health. The Samoan diseases such as hypertension, diabetes, and cancer
Studies Project – initiated in 1975 – is distinguished due to changes in diet and physical activity (Shephard
by the breadth of economic, demographic, cultural, and Rode, 1996). More recent research has integrated
a political–economic perspective to explore the influ- Defining “change”

ence of the collapse of the former Soviet Union on the
Deriving a meaningful operational definition of
health of indigenous populations (Leonard et al.,
“change” is a major challenge associated with research
2002; Sorensen et al., 2005; Snodgrass et al., 2006).
into the health consequences of cultural and economic
transitions. The vast majority of studies to date (well
Latin America
over three-quarters of those reviewed for this chapter)
Early research in Latin America focused largely on adap-
employ group-level, ecological comparisons of individ-
tation to high altitude, but attention soon shifted to
uals sharing a common biological and cultural history,
patterns of social relations and economic stratification
but currently living in divergent cultural and/or eco-
that shaped resource access, with implications for
nomic conditions. Comparisons across urban and
adaptive processes and health (Leatherman et al., 1986;
rural populations are particularly common.
Leatherman, 1998). For example, these investigations
For obvious logistical reasons, cross-sectional
revealed that factors linked to poverty – undernutrition,
designs are frequent, and were used in almost 90% of
infectious disease – played a stronger role than high
the studies reviewed for this chapter. In these studies,
altitude hypoxia in contributing to growth stunting
“change” is captured by making cross-sectional com-
(Leatherman et al., 1995; Leonard, 1989; Stinson,
parisons across two or more environments, where it is
1996). Research in Amazonia has considered a wide
assumed that the baseline environment will in the
breadth of topics, including changing patterns of infec-
future become similar to the environment used for com-
tious and parasitic diseases, blood pressure, diversity of
parison. Change is thus anticipated, but not directly
dietary strategies within shifting social and ecological
measured, within individuals. Only prospective studies
contexts, and socioeconomic factors affecting adult
can measure changes in cultural and economic environ-
nutritional status and work capacity (Reed et al., 1970;
ments within individuals across time. This approach
Dufour, 1983; Fleming-Moran et al., 1991; Fitton and
has been applied most productively to studies of
Crews, 1995; Dufour et al., 1997). Ongoing research in
migrants, where dramatic environmental changes can
lowland Bolivia is collecting repeat observations from a
be captured in relatively short lengths of time. Prospect-
population at the early stages of market integration in an
ive studies of in situ change are less common, but are
attempt to explicitly distinguish the effects of market,
important resources for assessing causal linkages
cultural, and ecological factors on health (Foster et al.,
between cultural and economic transitions and health
2005; Godoy et al., 2005c; McDade et al., 2005).
(Little and Johnson, 1987; Adair and Popkin, 1988;
Godoy et al., 2005a, 2005b).
Africa
Despite a high level of anthropological and public
health interest in Africa, relatively few studies have CULTURAL AND ECONOMIC TRANSITIONS,
explicitly investigated the health effects of cultural ADAPTATION, AND HEALTH: PATHWAYS
and economic transitions. Exceptions include import-
ant comparative research on blood pressure, investiga- There are several pathways through which cultural and
tions into changing patterns of fertility, and the economic transitions impact health (Figure 34.1). These
development of demographic models of shifting popu- processes are not mutually exclusive, and they inter-
lation dynamics (Scotch, 1963; Howell, 1979; Caldwell relate in complex and variable ways across different
and Caldwell, 1987; Hyatt and Milne, 1993). The
Turkana project has explored changing subsistence
and settlement patterns among Turkana pastoralists Changes in economic, social, political,
and/or cultural systems and contexts
in northern Kenya, and has revealed better health
among nomads with reference to child growth and
maternal nutritional status (Leslie et al., 1993; Little
et al., 1993; Shell-Duncan and Obiero, 2000). The recent
and rapid emergence of maternal obesity represents a Behavior Psychosocial
Environment/
new public health problem in urbanizing Africa, where natural resources stress
child stunting and wasting remain prevalent (Garrett Health care Demographics
and Ruel, 2005; Villamor et al., 2006). Despite the enor-
mous importance of these studies in underscoring the
complexity of the “nutrition transition” in Africa, most
data have been collected at the population level and
therefore cannot explore the within-household dynam- Mental and physical health
ics that may contribute to the simultaneous existence of 34.1. Primary pathways through which cultural and economic
malnutrition and overweight. transitions affect human health.
geographic, ecological, and historical contexts to shape prevalence of disordered eating behaviors, including
health through the mechanisms of adaptation outlined self-induced vomiting to lose weight, followed pro-
above. longed television viewing among adolescent girls in Fiji
(Becker, 2004). Becker notes that “the impact of
televisions appears especially profound, given the
Behavior
longstanding cultural traditions that previously had
Cultural and economic transitions initiate behavioral appeared protective against dieting, purging, and body
changes that may have dramatic implications for pat- dissatisfaction” (Becker et al., 2002, p. 511).
terns of diet and physical activity. A number of studies
have documented shifts in energy balance resulting
Health care
from reductions in physical activity and increased con-
sumption of calorie-dense foods as populations move For many populations, early stages of acculturation
from a labor-intensive, subsistence-based diet to a par- and market integration provide for the first time reli-
tial or complete reliance on commercially prepared able access to primary health care, vaccines and anti-
foods. In places like the Samoan Islands, these behav- biotics effective against a wide range of infectious
ioral changes have fueled the rapid emergence of epi- diseases, and new explanatory models for the preven-
demics of obesity and chronic degenerative diseases tion of disease grounded in germ theory (Akin et al.,
(McGarvey et al., 1993; Keighley et al., 2007). On the 1985; Gage, 2005). The implications for child health
other hand, for marginally nourished populations, the and survival may be particularly dramatic. For
availability of commercial foods – and the means to example, among Venezuelan lowlanders, economic
acquire them – has been associated with better nutri- changes provided households tied to the market with
tional status by improving dietary diversity and the greater access to medical services, and cash from wage
quantity of macronutrients (DeWalt, 1983). labor allowed them to purchase health care (Holmes,
Breast-feeding is a critical determinant of infant 1985). A by-product of emerging markets is the credit
health in low-income settings, and contextual factors system, which can smooth shocks by providing the
that discourage breast-feeding may therefore have dra- means to borrow money to pay for medicines and
matic implications for infant morbidity and mortality health services during times of need (Amin, 1997;
(McDade and Worthman, 1998). The availability of Godoy, 2001). Access to a well-functioning credit
infant formula may discourage breast-feeding, particu- system may also buffer vulnerable individuals from
larly when there are competing demands for a mother’s nutritional shortfalls, and prevent the further deterior-
time and energy (Nerlove, 1974), and when formula is ation of health from fluctuating food consumption that
perceived to represent a more advanced, technological, impairs ability to work, whether at a subsistence level
or “modern” option (Manderson, 1982). or for cash wages (Rose, 1995; Morduch, 1995).
In addition to changes in patterns of diet and phys- In contrast, access to Western biomedical models
ical activity, health may be affected by the emergence of and treatments may actually impair health, as in the
risk behaviors such as smoking or excessive alcohol con- case of the global distribution and promotion of infant
sumption. Alcoholism was pronounced among Native formula as a substitute for breast milk (Post and Baer,
Americans undergoing forced assimilation in the United 1978). Women in rural Kenya who deliver their babies
States (Graves, 1976), emerged as an adolescent in hospitals are twice as likely to feed their infants
response to colonial stress in the Arctic (O’Neil, 1986), formula (Cosminsky, 1985). In rural Mexico, women
and has soared in communities that are becoming enga- who seek care in a local hospital introduce supplemen-
ged in the regional market economy in lowland South tal foods to their infants earlier than women not near
America (Godoy et al., 2006). While social and economic the hospital since medicines used in hospitals are
transitions have been associated with increased alcohol believed to enter breast milk and make breast-feeding
use across a variety of populations, perhaps nowhere dangerous (Millard and Graham, 1985). In other set-
have the effects of rapid change on substance abuse been tings, formula may be given to mothers in hospitals or
more pronounced than in the former Soviet Union. The prescribed by physicians, thereby associating formula
fall of the Soviet government led to calamitous economic with modern medicine (Manderson, 1982; Simpson,
collapse, with wide-ranging ramifications for health and 1985). The rapid spread of formula can be attributed
well-being. This “failed modernization” and the resulting to an aggressive global marketing campaign mounted
health crisis has contributed to a declining life expect- by formula manufacturers, and it was not until grow-
ancy, largely due to increased mortality from lung cancer ing concerns regarding the contribution of formula use
and alcohol-related cardiovascular failure in men to rising rates of infant mortality that the campaign
(McKee, 2005; Sorensen et al., 2005). was stopped.
Associations with risky health behaviors may also Another level of complexity is added when tensions
be more indirect. For example, an increase in the arise between mothers and public health policy makers
regarding recommendations for breast-feeding prac- of Akwesasne Mohawk youth, increased blood lead
tices in the context of epidemic HIV, especially in levels predicted a substantial delay in the timing of
Africa. For HIV-positive mothers, breast-feeding con- menarche (Denham et al., 2005). Studies of the organic
fers a 15–20% risk of mother-to-child-transmission pollutants polychlorinated biphenyls (PCBs), have
(Atashili et al., 2008). However, this risk must be revealed reduced birthweight in infants born to PCB-
balanced against the concerns of malnutrition and exposed mothers (Schell et al., 2006), and a negative
mortality attributed to an increased susceptibility to association between adolescent PCB levels and meas-
infectious disease contracted from water-based formu- ures of long-term memory (Newman et al., 2006). The
las. Careful evaluation of the pros and cons led the potential for intergenerational transmission of these
World Health Organization to recommend exclusive pollutants may be especially profound, as these lipo-
breast-feeding for 6 months of life even for HIV- philic toxins are concentrated in human fat cells where
positive mothers, as breast-feeding remains a major they can be transferred in utero to the developing fetus
protector of child survival in sub-Saharan Africa and to infants via breast milk (Schell and Knutson,
(Coutsoudis et al., 2008; David et al., 2008). 2002; also see Chapter 33 of this volume).
Closely related to changes in the physical environ-
ment is the possibility that cultural knowledge
Environment and natural resources
regarding the use and management of local natural
Rapid alterations in the local physical environment can resources will be lost as a result of acculturation. Local
have significant implications for health. Although few ecological knowledge serves as a guide for activities
populations rely exclusively on local natural resources central to survival and well-being, including effective
for subsistence, rapid population growth and intensifi- habitat management, subsistence and food procure-
cation of agriculture put pressure on natural resources. ment, and attempts to prevent and cure disease
Among slash and burn horticulturalists, market inte- (Brookfield and Padoch, 1994; Atran and Medin,
gration is associated with more rapid deforestation 1997; Etkin, 2000; Pandey, 2001). Cultural and eco-
and intensification of farm production (Vadez et al., nomic transitions may threaten this knowledge if
2004), while constraints on land use encourage formal schooling and integration into emerging market
nomads to shift from pastoralism to farming (Little economies prioritize alternative sources of informa-
and Leslie, 1999; McCabe, 2003). These changes may tion and provide access to substitute products not
have implications for the sustainability of natural made from local resources (Godoy et al., 1998; Reyes-
resource use, as well as for the quality and quantity of Garcia et al., 2005). Recent research in lowland Bolivia
nutrients extracted from the local environment. has demonstrated the potential cost to health if this
In addition, increases in population density knowledge is lost: adults with better knowledge
resulting from and contributing to agricultural intensi- regarding the availability and potential uses of local
fication facilitate the spread of infectious disease, as ethnobotanical resources have healthier children, as
does more frequent contact with outsiders, particularly indicated by higher measures of nutritional status
in the absence of improvements in sanitation and and lower levels of infection (McDade et al., 2007).
hygiene (Jenkins, 1989). Initial exposure to novel infec-
tious diseases has in some cases had devastating conse-
Demographic processes
quences for indigenous populations, leading to dramatic
rates of mortality, as well as social and economic Classic demographic transition theory states that as
upheaval (McNeill, 1977). Recent research in lowland living conditions improve in preindustrial populations
Bolivia has documented higher concentrations of mortality rates will drop – particularly for infants and
C-reactive protein (an indicator of inflammation) in chil- children – and life expectancy will increase (Caldwell,
dren regularly attending school compared to children 1976). Declining fertility rates will follow, thus com-
not in school, suggesting that the relatively recent intro- pleting the transition from high rates of birth and
duction of formal schooling may promote pathogen death, to low rates of birth and death in industrialized
transmission in this population (McDade et al., 2005). settings. Over the last 200 years, global life expectancy
In urban (and urbanizing) environments, industrial in industrialized populations has more than doubled,
development and rapid increases in population density from about 25 to 65 years for men and 70 years for
may outpace the management of organic waste and women (Oeppen and Vaupel, 2002), and rates of total
other forms of pollution, such as noise, air, mercury, fertility have dropped to about 2 children in industrial-
and lead (Schell and Denham, 2003). Exposure to ized nations since World War II. In comparison, total
environmental pollutants may be particularly severe fertility rates in the developing world are far higher,
for children, who may experience impairments in likely due to the lack of contraceptives and less access
endocrine function, physical growth, and cognitive to education in these populations (Caldwell and Cald-
development as a result. In a community-based study well, 1987). This represents an idealized model of the
complex relationships among socioeconomic and into life on reservations near the forest. State and mis-
demographic changes that may apply to many popula- sionary interventions, changes in diet, and access to
tions in transition, with important implications for Western medicines have resulted in reduced mortality
health. Local processes of demographic change may rates compared to life in the forest at all ages except for
also deviate substantially from this model. the first year of life, when rates of infant mortality are
As standard of living improves adolescent girls and actually higher on the reservation.
boys reach puberty earlier, lowering the age at which During life in the forest, the total fertility rate was
successful reproduction is possible (although social, cul- 8 live births per woman, with an interbirth interval
tural, and/or economic factors may encourage delayed of 37.6 months, and an average age of first birth of
childbearing). Lactational amenorrhea – induced by a 19.5 years (Hill and Hurtado, 1996). On the reserva-
neuroendocrine cascade initiated by frequent nipple tion, women start reproducing nearly 2 years earlier at
stimulation – increases interbirth intervals in noncon- 17.7 years of age, and have more live births (8.5)
tracepting populations (Konner and Worthman, 1980; at interbirth intervals that are 6 months shorter (31.5
Vitzthum, 1994). The availability and use of supplemen- months). This accelerated reproductive schedule may
tal infant foods may interrupt this process and lead to have implications for women’s health, infant, and child
rapid population growth, as well as increases in rates of well-being, as well as population growth for the Aché.
infant morbidity (McDade and Worthman, 1998). Sexu-
ally transmitted diseases and patterns of secondary ster-
Psychosocial stress
ility may also reduce fecundity (Caldwell and Caldwell,
1983; Ellison et al., 1986; Hill and Hurtado, 1996). Changes in neuroendocrine activity are an essential
Cultural transitions may also encourage shifts in part of the “fight-or-flight” response in all vertebrates.
the number of children desired by adults, and in pat- For most species these are critical adaptive responses
terns of parental investment. Greater parental invest- to social and ecological stressors, but the metabolic
ment in offspring education, a smaller desired family consequences may be more profound for humans
size, and a delay in the onset of reproduction, as well as who experience the same hormonal activation in
a reduction in total number of offspring can result in response to purely psychosocial stressors (Sapolsky,
reduced- and below-replacement fertility (Levine, 2004). Stress has been shown to be an important deter-
1994; Leslie et al., 1994; Kaplan et al., 2002). In Kenya, minant of mental and physical health for humans
for example, increased female education was associ- (McEwen and Lasley, 2002; Cohen et al., 2007), and
ated with a substantial decrease in the number of may therefore be a significant mediator of the health
births (Hyatt and Milne, 1993). In such situations, impact of cultural and economic transitions. Psycho-
parents may perceive increased “costs” associated with social stressors initiate the activation of multiple neu-
raising children that motivate shifts in patterns of fer- roendocrine pathways, including the sympathetic
tility and child rearing (Caldwell and Caldwell, 1987). adrenal medullary system (SAM), and the hypothalamic-
Rapid population growth following accelerations in pituitary-adrenocortical (HPA) axis, which in turn
reproductive schedules and/or declines in infant mor- cause changes in cardiovascular, metabolic, and
tality may increase population density, thereby facili- immune system activity (Johnson et al., 1992;
tating the transmission of pathogens and increasing McEwen, 1998). Short-term responses facilitate
rates of infectious diseases (Barrett et al., 1998). Popu- adaptation to a wide range of stressors, but frequent
lation growth may also put strain on local natural or excessive demands contribute to poorer health
resources, and serve as an impetus for outmigration outcomes. The operationalization of stress poses sig-
and urbanization (Armelagos et al., 1991, 2006). nificant challenges to cross-cultural research, since
Demographic data from the Aché – a small indigen- self-report measures of perceived stress or symptoms
ous population of eastern Paraguay – underscore many of emotional distress (e.g., depression, anxiety) com-
of these points. Until relatively recently, the Aché lived monly used in Western countries may not be valid in
in small, mobile bands and subsisted by hunting different linguistic and cultural contexts. Physiological
animals and gathering plants and insects in the forest measures provide relatively objective indicators of
(Hill and Hurtado, 1996). During this period, age-specific stress that are comparable and interpretable across
mortality rates were high compared to contemporary different populations (despite cultural and linguistic
industrial populations, but similar to other foraging differences), and that provide insight into the bio-
populations. Even though rates of infant and child logical pathways that may lead to impaired health
mortality were particularly elevated, approximately (Ice and James, 2007). For this reason a number of
one third of all Aché born lived to the age of 60. First studies have investigated the impact of cultural and
contact with outsiders in the 1970s brought epidemics economic transitions on biomarkers of stress.
of infectious diseases that killed nearly 40% of the The potential impact of rapid social change on
population, and since that time the Aché have settled stress and health has long been recognized, with early
work emphasizing ambiguity and conflict resulting drawn on by individuals in times of need (Kawachi,
from discordance between traditions and expectations 2000). In preindustrialized settings social capital may
set up during childhood socialization, and a rapidly be a particularly important resource for protecting
changing cultural environment encountered in adult- against shocks such as illness or poor foraging/
hood (Scotch and Geiger, 1969; Henry and Cassel, agricultural returns (Godoy et al., 2005a). This has led
1969; Cassel, 1974). Several studies demonstrate sig- to the hypothesis that as markets develop in preindus-
nificant effects of acculturation on the frequency of trialized settings and socioeconomic stratification
self-reported symptoms of physical and emotional emerges, health may suffer due to an erosion of social
distress (Graves and Graves, 1979, 1985; Hanna and capital. Associations are mixed, with market integration
Fitzgerald, 1993). Extensive work with Samoan popu- leading to distrust, conflict, and attenuation of norms of
lations has associated the “modernization” gradient sharing in some populations (Putsche, 2000; Bury,
with increases in blood pressure and catecholamine 2004). In other settings, new market activities work
levels (McGarvey and Baker, 1979; Baker et al., 1986; within existing structures of social capital, and norms
Pearson et al., 1993; McGarvey, 2001). Similarly, of sharing and reciprocity help distribute the benefits of
individual-level measures of stressors associated with market participation and attenuate the negative effects
culture change predict increases in blood pressure, of socioeconomic stratification (LeFerrara, 2003).
catecholamine concentrations, and reductions in
cell-mediated immunocompetence (Dressler et al.,
1987; James et al., 1987; McDade, 2002). A recent
ACCULTURATION AND HEALTH: MODELS
meta-analysis suggests that acculturative distress is a
stronger predictor of increases in blood pressure than
Investigators have employed a number of conceptual
other obvious correlates of lifestyle such as dietary
and analytical models in their efforts to evaluate the
change and physical activity levels (Steffen et al., 2006).
impact of cultural and economic transitions on health.
The vast majority of research investigating associ-
These models serve as guides for hypothesis testing
ations between acculturation and stress has been con-
and the interpretation of results, and reveal assump-
ducted with adults, with a few noteworthy exceptions.
tions regarding how contextual factors relate to health.
In rural Samoa, school attendance has been associated
Four general classes of models have been used to guide
with increases in catecholamine production in young
prior research (Figure 34.2).
children (Sutter, 1980). Recent work has shown that
status inconsistency is associated with psychosocial
stress (as indicated by a biomarker of cell-mediated Additive models: more is better (or worse)
immune function) in Samoan adolescents (McDade,
2002). In a study of exposure to tourists in Nepal, chil- Of fundamental importance is a meaningful represen-
dren living along a trekker’s trail were taller and heavier tation of aspects of the surrounding environment that
with greater BMI than rural children. However, these may have implications for individual well-being. Addi-
children also had significantly higher blood pressure, tive models (Figure 34.2a) assume that exposure to, or
with girls exhibiting greater increases associated with
living along the trail than boys (Pollard et al., 2000). (a) (b)
In addition to affecting stressor exposure, cultural 1 2 3
and economic changes may alter sources of social sup-
Health
Health
port that individuals can draw on to buffer the adverse

health effects of stress. For example, in the Andes, a
strong involvement in wage labor, particularly among
migrants, impeded access to familial or extra-familial
Change → Change →
sources of support (Carey and Thomas, 1987). Simi-
larly, Polynesian men who retained a more traditional (c) (d)
Status marker2 →
group orientation reaped the benefits of better health C

1
while “modernizing,” as opposed to those men who did inconsistency consistency
= ↑ stress = ↓ stress
Health
not retain social contacts (Graves and Graves, 1979).

Recent research in industrialized countries has
consistency inconsistency
underscored the importance of social capital as an 2 = ↓ stress = ↑ stress
attribute of communities that may be protective for
health (Kawachi, 1999; Subramanian et al., 2005). Change → Status marker1 →
Social capital refers to institutions, norms of trust 34.2. Four general types of conceptual models (a–d) used to
and reciprocity, and social networks that facilitate col- evaluate the association between measures of cultural and eco-
lective action for the common good and that can be nomic change and measures of health.
engagement with, nontraditional ways of living is that are more proximate to health outcomes than
associated with health in a roughly linear fashion in a possible with ecological comparisons.
given population, such that a dose–response relation-
ship can be detected between environmental changes
Curvilinear models
and changes in health. The vast majority of these stud-
ies employ ecological comparisons, although a signifi- In general, additive models attempt to represent the
cant number include individual-level measures of association between change and health in a linear fash-
experience as well. ion: cultural and economic transitions lead to rapid
Ecological models employ group-level comparisons changes in the local sociocultural landscape, posing
of individuals sharing a common history, but currently adaptive challenges that may compromise health.
living in divergent geographic locations that differ in A variant of the additive model is an explicit consider-
some meaningful way. In these studies, geographic loca- ation of curvilinear or threshold associations (Figure
tion provides a proxy for exposure to, and engagement 34.2b). These models are similar in that they investi-
in, novel social, cultural, and/or economic systems. This gate the impact of a single dimension of culture change
approach has been critical in underscoring the import- on health, but they differ in that they do not assume a
ance of acculturation to health in diverse populations linear, dose–response relationship. Within a single
around the world, and has provided a solid foundation population, early stages of acculturation may have
for future research (Patrick et al., 1983; Jenner et al., negative effects on health, with later stages having
1987; Wessen et al., 1992; Ulijaszek et al., 2005). positive effects (or vice versa). Alternatively, the asso-
Ecological studies are easy to implement, but they ciation between acculturation and health may reach
are limited in that causation is impossible to ascertain the point of diminishing returns, resulting in a
with group-level comparisons, and confounding is pos- J-shaped or threshold pattern.
sible as group differences in health may be due to For example, among Filipino immigrants to
factors other than acculturation. In addition, assump- Hawai’i, intermediate levels of “culture contact” were
tions about the nature of the difference in experience associated with elevated stress hormone levels, while
between groups need to be evaluated, and substantial more favorable stress hormone profiles were found in
heterogeneity within the comparison groups may be immigrants with low and high levels of contact
obscured. (Brown, 1982). Recent research in Brazil reveals a
For example, a number of studies use urban resi- curvilinear relationship between body composition
dence as an indicator of acculturation, but in the and socioeconomic status that differs between men
Philippines, type of neighborhood within an urban area and women: People living in the favela – an impover-
is a major determinant of access to basic infrastructure, ished squatter neighborhood – were the smallest and
health care services, educational opportunities, and leanest, with adiposity increasing and then leveling off
socioeconomic resources (McDade and Adair, 2001; for men with higher levels of socioeconomic resources.
Dahly and Adair, 2007). Rural settlement types are Adiposity also increased with socioeconomic status for
comparably diverse, with some rural areas looking women in the middle class, but then dropped for
more like urban areas on multiple measures of environ- upper-class women, who were lean compared to
ment. In this context, a simple urban–rural dichotomy women in the middle class (Dos Santos et al., 2001).
fails to capture significant variation in experience, and Findings like these hint at the complexity of cul-
would be a poor representation of reality for analyses of tural and economic change, and curvilinear associ-
the impact of urbanization on health. ations with health may be more common than often
Household- or individual-level measures avoid assumed based on research with additive models. Syn-
some of these shortcomings by creating scales that chronically, a linear relationship between accultur-
quantify behaviors, attitudes, and/or experiences rele- ation and health may be evident if the range of
vant to cultural or economic change that can then be cultural variation is truncated. If Figure 34.2b repre-
used as predictors of health. For example, in Samoa, sents the association between acculturation and health
a “Western Profile” index – summing information on in a given population at a given point in time, this
English language ability, travel, relatives overseas, edu- relationship would look like a negative linear relation-
cation, and parental occupation – has been positively ship if analyses were limited to the lowest third of the
associated with urinary catecholamine excretion in acculturation distribution. Recent research in the
men (James et al., 1987). Similarly, in central Mexico, islands of Samoa underscores this point (Ezeamama
higher blood pressures have been reported for adults et al., 2006). In the more economically developed area
engaging in behavioral and material aspects of a of American Samoa, individual-level measures of
“modern” lifestyle (Dressler et al., 1987). Individual- socioeconomic status were inversely related to risk
level assessments recognize the diversity of experience factors for cardiovascular disease, a pattern similar to
within communities, and provide measures of experience that found in most Western nations. But in nearby
Samoa, where economic development has progressed have divergent effects on different health outcomes.
more slowly, socioeconomic resources were positively For example, as noted above, Westernization in the
associated with cardiovascular risk. islands of Samoa has been associated with a general
Diachronically, a different pattern of relationship pattern of increased burdens of morbidity in adults as
between change and health may emerge. If the x axis in indicated by multiple measures of cardiovascular and
Figure 34.2b represents cultural change over time, an metabolic disease risk (Baker et al., 1986). This rela-
analysis of the association between acculturation and tionship can be represented by line #2 in Figure 34.2c.
health in the earliest stages of acculturation (indicated However, these transitions are also associated with
by #1) would reveal a negative association. The same declines in mortality – infant mortality in particular –
analysis conducted at a later point in time (indicated which are in turn associated with increases in life
by #3) would reveal a positive association. Three expectancy, an undisputable indicator of positive
decades of data collection in the Samoan islands has health. These improvements in health can be repre-
been able to document a shift in the association sented by line #1 in Figure 34.2c, and underscore the
between socioeconomic status and cardiovascular dis- point that it cannot be assumed that the implications
ease risk, underscoring the value of longitudinal of cultural and economic transitions for health will be
research. Unfortunately, few studies have the breadth uniform across health indicators.
or time depth to consider the full range of variation in
cultural and economic factors that predict health in a
Inconsistency models
population, and this fact may be a major reason for
inconsistency in results drawn from studies conducted Inconsistency models diverge from other approaches
in different regions, and at different points in time. in that they simultaneously explore multiple dimen-
sions of change in an attempt to capture the tensions,
conflicts, and ambiguities that arise within individuals
Heterogeneity models
living in the context of cultural and economic transi-
In their simplest form, additive and curvilinear models tions. These models do not assume that acculturation
assume that cultural and economic transitions have is related to health in an additive fashion; instead, it is
uniform affects on the health of all individuals in a the social and/or psychological dissonance associated
population. Clearly, this need not be the case, and ana- with rapid change that may be causal. Inconsistency
lyses vary in the degree to which they explicitly evaluate models rely primarily on psychosocial pathways
the degree of heterogeneity in responses to change. linking experience and health, and have therefore been
Historically, the emergence of agriculture has been applied most frequently to physiological outcomes
a fundamental transition for human populations with related to stress.
dramatic implications for health (Cohen, 1989). The Models of status inconsistency recognize that an
intensification of agriculture, and related trends individual’s social status is derived from multiple
toward population growth, central organization, and sources, and that these status markers are used to
labor specialization promote the unequal distribution advertise a certain style of life or social worth (Dressler,
of resources, including resources related to health. For 1988). Changes in the sociocultural landscape foster
example, paleopathological evidence from Chile circa the emergence of new, locally meaningful markers of
1000 BP indicates that the intensification of agricul- social status. To the extent that these markers are in
ture was associated with a general decline in health agreement within individuals, a coherent social iden-
(#2 in Figure 34.2c), but this decline was not equally tity is projected. However, disagreement – or status
distributed. Shaman men – a privileged class – showed inconsistency – may invalidate an individual’s claim
little evidence of poor health (#1 in Figure 34.2c) and to a certain social standing, thereby resulting in stress
were much better off than men in general, who in turn (Figure 34.2d). Models of status inconsistency repre-
were in better health than women in this population sent more dynamic measures of individual experience
(Allison, 1984). This stratification in health is not evi- vis-à-vis culture change than additive models that may
dent in analyses from earlier historical periods when be particularly relevant to the experience of stress.
the society was more egalitarian, and emerges only In the context of globalization, Western material
with the social and economic transitions associated goods and lifestyles tend to be associated with high
with agricultural intensification. It is important to status around the world, while developing economies
inspect for within-population heterogeneity in associ- cannot provide enough high-paying jobs to support the
ations between change and health since averaging demand for increased levels of consumption. This
across subgroups may lead to the mistaken conclusion sets the stage for “lifestyle incongruity,” or inconsist-
that change is not associated with health. ency between emerging symbolic signs of prestige
Acculturation may lead to stratification in health (e.g., material style of life, travel, etc.) and occupa-
across social groups within a population, but it may also tional/educational class. Independent of potentially
confounding variables, adults who are incongruent on foundation on which to build more sophisticated
these two dimensions of social status have been found models that attempt to capture this variation. There is
to have elevated blood pressure in Samoa, St. Lucia, tremendous potential to develop new conceptual and
Mexico, and Brazil (Dressler, 1982, 1990; Dressler and analytic models that link context, behavior, and health
Bindon, 1997; Dressler et al., 1987a, 1987b). at the individual level, across time. By thinking critic-
Other formulations of status inconsistency have ally and creatively about how to define and measure
been developed for specific ethnographic settings. For shifting social, cultural, and economic contexts, and by
men in American Samoa, having a high status job but linking these measures to physiology and health, we
relatively low educational status has been associated greatly enrich our understanding of human biology
with elevated blood pressure (McGarvey and Schendel, and processes of adaptation.
1986). Increased blood pressure among young men has
also been attributed to increased financial demands
from extended family (Bitton et al., 2006), while for DISCUSSION POINTS
Samoan women, “living beyond one’s means” has been
associated with elevated blood pressure (Chin-Hong 1. Is globalization good or bad for health? Why is a
and McGarvey, 1996). For Samoan migrants in Califor- definitive answer to this question elusive?
nia, economic status and leadership in the local com- 2. What are the primary mechanisms of human adap-
munity have been identified as two important tation, and how do they provide insight into the
dimensions of social status, with inconsistency across impact of cultural/economic transitions on human
these dimensions associated with increased blood pres- health?
sure (Janes, 1990). For Samoan adolescents, discord- 3. What approaches have been applied to model the
ance between a traditional marker of social status impact of cultural/economic transitions on human
(having a matai chief in the household) and a new biology and health? Which models best capture
marker of social status (familiarity with Western life- which types of issues?
styles) has been associated with increased Epstein– 4. What are the gaps in current knowledge? What
Barr virus (EBV) antibody titers, indicating suppressed future research is needed to address these gaps?
cell-mediated immune function (McDade, 2002).
Inconsistency models are significant in that they
attempt to capture complex sociocultural processes in
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Index
Locators in bold refer to major content

Locators in italic refer to figures/tables
Locators for headings which also have subheadings refer to general aspects of that topic only.
AAAG (American Association of adaptation 17, 21, 25–26; schizophrenia/schizotypal

Anthropological Genetics) 41 see also altidudinal adaptation, disorder 552
AAPA (American Association of developmental adaptation, thrifty adaptive radiation 14;
Physical Anthropologists) 32, genotypes, thrifty phenotypes see also evolutionary theory
144, 266 acclimation 19 additive genetic variance 4
abdominal fat 102, 430, 432, 518, 520; acclimatization 19 additive models of cultural transition
see also adipose tissue, metabolic accommodation 20 591, 592
syndrome, obesity cooperation as 22, 383–384 ADHD (attention-deficit hyperactivity
ABO blood groups see blood groups and cortisol 414 disorder) 496
Aboriginals, Australian 497 cost-benefits 25 adipose tissue/adiposity 23, 519,
genoclines 222–223 cultural/technological 20, 582–584; 519–520; see also metabolic
markers of variation 222 see also cultural transitions syndrome, obesity, size/
microevolutionary processes 233 definition 170 morphology
protein hormones 129 discussion points 26 abdominal fat 102, 430, 432, 518, 520
size/morphology 164, 167 domains 171 brain development/function 431
abridged life tables 76 ecological variation 338 endocrinology 135
acclimation 19, 170, 174–175; embodied capital 440–441, 452 fecundity 327
see also altidudinal adaptation endocrinology, behavioral 277 global distributions 166
accommodation 20, 398; epigenetics 24–25 infant 325, 520
see also adaptation fetal 324, 341–342 inflammatory response 523
acculturative stress model 585; functional 19 insulin resistance 499
see also cultural transitions, stress genetic 20–21, 170, 176, 184–185, 491 juveniles/adolescents 400
accuracy, definition 96 habituation 19 natural selection 521
ACE (angiotensin-converting enzyme) history of discipline 34, 37–38 pregnancy/lactation 339–340
184–185 immune system 462–463 prenatal nutrition, role 523–524
Aché people 135 individuals vs. populations 20 rebound 400
adolescence 387–388 information processing as 408 aDNA (ancient DNA) research 146–147
consumption/productivity 443 modeling 10 adolescence see juveniles/adolescents
demographic transition 590 molecular 253 ADP (air displacement
life history theory 441, 441–442 nutritional 37 plethysmography) 118–119
marriage 389 and pollution 566–567 adrenarche 131, 358–359, 410
senescence 360 polygenic inheritance 58–59 adrenocorticotropic hormone
survivorship 79 processes 18–19 (ACTH) 414
testosterone levels, male 364 reproductive biology 327–328, aerobic capacity, altitudinal
achondroplasia 63, 68–69, 69–70 362–363, 364 adaptations 171, 175–177
acne 496 research directions 23 affection, biology of 287, 411;
acromion process measurements size/morphology 166 see also attachment,
106, 107 skin coloration 201 endocrinology, pair bonds
ACTH (adrenocorticotropic to stress 17–18, 36, 417, 582 affluence, afflictions of 491, 493;
hormone) 414 adaptationist paradigm, evolutionary see also metabolic syndrome,
activational effects 280 medicine 459–460 obesity
active tissue mass 122 anorexia nervosa 554 aflatoxins in food 399
activity see physical activity depression/mania 553, 554 Africa 252, 587; see also out-of-Africa
acute disease, causation 503 evolutionary psychiatry 551, 560 hypothesis
acute mountain sickness (AMS) 172 mania/hypomania 553–554 African Ancestry Project 147
603
604 Index
African replacement model 250 oxygen transport 172–174, 180 brain energetics 429
African sleeping sickness 467 pulmonary ventilation during differential parental investment 316
Afro-Caribbean peoples 271 exercise 181 DNA markers 253
Age of Exploration 29 pulmonary volume 175, 176, 181, 182 endocrinology 135, 278
age of maximum reproductive reproductive performance 177–180 immune system 465, 466, 467, 468
potential (MRP) 529 research directions 185–186 inbreeding avoidance 312
age-specific fertility rates (ASFR) resting ventilation 180 leptin structure/function 135
80, 381 ventilatory control/chemosensitivity longevity/senescence 533–535, 538,
age-specific gene action 529–530 180–181 540–541, 543, 545
age-structured populations 76 altricial offspring 537, 538, 542, major histocompatibility complex 315
aggregate approach, pollution, 543, 544 male reproductive function 572
environmental 567 altruism 11, 12, 22, 278, 555; mate choice 353
aggression, endocrinology of 281, 283, see also co-operation, group pair bonds/parental care 281–282, 413
353–354, 461 selection sex differences in behavior 280
aging 31, 54, 195, 359, 528; alveolar ventilation (VA) 172 sleep 430
see also late-life stage, longevity/ Alzheimer’s disease 233, 503, 511, 512 social factors and development 358
senescence Amazon, cultural transitions 587 t gene locus 11
agricultural societies 444–445, amenorrhea 136, 325–327 time management 136
445–446, 449, 497; America, human migration/gene ankylosing spondylitis (AS) 230
see also foraging societies, flow 252 Annals of Human Biology 41
Homininae, horticultural societies, American Association of Anthropological Anopheles spp. 474–477
thrifty genotypes, traditional Genetics (AAAG) 41 anorexia nervosa 326, 399, 554, 555,
human populations American Association of Physical 559; see also eating disorders
cultural transitions 591, 593 Anthropologists (AAPA) 32, 144, 266 anterior cingulate cortex 429
horticultural societies 444–445, 449 American Indians 497 anterior superior iliac spine
and life span 540 American Journal of Human Biology 41 measurements 107
AIDS see HIV/AIDS American Journal of Physical anthrax 469
air displacement plethysmography Anthropology (AJPA) 32 anthropological demography 88;
(ADP) 118–119 amino acids, gene expression 57 see also demography
air pollution 568, 570, 572, 574–575, AMS (acute mountain sickness) 172 anthropological genetics 39;
574–575; see also pollution amygdala 426 see also genetics
AJPA (American Journal of Physical amyotrophic lateral sclerosis 41 Anthropological Genetics (Crawford
Anthropology) 32 anabolic steroids 352 and Workman) 224–225
Al Naskapi 216–217 anatomically modern Homo sapiens anthropology 29, 32, 566–567;
albinism 193 (AMHS) 245–250 see also physical anthropology
albumins 216–217 ancestry 227; see also race/typology anthropometers 105–106
alcohol burn 115 ancient Egypt/Mesopotamia 446; Anthropometric Standardization
alcohol use/abuse 493, 496, 497, 558, see also traditional human Reference Manual (Lohman et al.) 96
588; see also substance abuse populations anthropometry 92; see also body
allelic interaction 50 ancient DNA (aDNA) research 146–147 composition studies
Allen’s Rule 36, 157, 166, 167, 222 Andean Biocultural Studies project 38 abdominal circumference 102
allergies 460, 464, 539 Andean peoples 177 acceptable error limits 106
allocation principle 9 altidudinal adaptation 170 anthropometers 105–106
allopatric speciation 13 birthweight 178 applications other than child
allostatic load 414 fertility/fecundity 177–178 growth 110
altidudinal adaptation 17, 18, 23, 41, juvenile/adolescent growth 401 body composition studies 117–118
170–171 markers of variation 224 buttock/hip circumference 102
acclimatization 174–175 maternal oxygen transport 179 calibration 102
arterial oxygen saturation 181–182 native endurance performance 177 climatic influences on body weight/
blood gases/pulmonary gas psychosocial stress 591 proportions 159
exchange 182–183 pulmonary volumes 129, 175, 176, 182 data handling 97–98
cardiovascular system 183 androgens 131–132; see also males, diameters 104
discussion points 186 steroid hormones, testosterone discussion points 110–111
environmental hypoxia 171–172 andropause 352, 359–360 infant measuring tables 102
genetics 184–185 anemia 179, 218 infantometers 102
hemoglobin 183–184 Angelman syndrome 61 instruments/techniques 93–96, 98, 99
infancy/early childhood growth angiotensin-converting enzyme (ACE) measurement units 93
176, 399 184–185 measuring procedures 98–99
juvenile/adolescent growth 401 animal studies; see also nonhuman neonatometers 101–102
muscle structure/metabolism 184 primate studies nutritional status assessment 167
native work capacity 175–177 alcohol use 558 reliability 96–97
Index 605
skinfold callipers 37–104 attention-deficit hyperactivity disorder biceps brachii measurements 107
skinfolds 103 (ADHD) 496 bi-iliac diameter 105
stadiometers 100–101 attraction, mate 352 biocultural approaches, human biology
stature 99–100 Australia, markers of variation 224; 35–36; see also anthropology,
subscapular skinfold 103, 104 see also Aboriginals culture
supine/recumbent length 101, 102 Australopithecines 426; biocultural evolution 535,
surface landmarks 106–110 see also Homininae 542–543, 544
tape measures 102–103 autistic spectrum disorders 557–558 biodiversity, and emerging diseases 477
technical error of measurement 96, autoimmune diseases 461, 463, 464, bioelectrical impedence analysis (BIA)
106, 106 467, 495, 540 116, 120
technological advances 110 automated data collection, bioethics 144–145; see also ethics
terminology 92–93 anthropometry 110 Biological Anthropology and Ethics
training 99 auxology 32, 94; see also growth (Turner) 144
triceps skinfold 103 avian flu 479 biological species concept (BSC) 12
weight measurements 99 AVP (arginine-vasopressin) biomagnification 568
antibiotic medication 470–471, 494 see vasopressin biomarkers of disease 492;
antibody-mediated immunity 463 Aymara peoples 170 see also markers of variation
anti-inflammatory effects, statins 505 Aztec peoples 446 biomedical anthropology 41
antimicrobial effects, garlic 505–506 biomedical models of health 588
antioxidants 493; see also free radicles B cells 462–463 biostatistics, use of 32
The Antiquities of the Jews baby fat 325, 520 bipedalism 389
(Josephus) 268 Baker, Paul T. 35–36 biphenol A 25
anxiety 282–283, 329, 461, 496, 559 balancing selection 7, 69–70 bipolar disorder 553–554
APOE*4gene 536 Bangladeshi women, ovarian bird flu 479
apoptosis 507, 508–509, 529–530, function 325 birth 131, 133, 407
532–533 Barnicot, Nigel A. 34, 37 birthweight
appearance-based mate choice basal metabolic rate (BMR) 122–123, altidudinal adaptation 178, 179
297–298 340, 360–361, 383, 520 and disease 24, 341
apple-shaped bodies 499 basophils 461 life span approach 40–41
apprentice hypothesis 387 Bateman’s principle 352 and race/typology 273
archetypes 560 BCM (body cell mass) 117, 118, 123 reproductive hormone levels
Arctic peoples 586–587 BDD (body dysmorphic disorder) 110 324–325
arginine-vasopressin see vasopressin BDNF (brain derived neurotrophic bivariate scatter plots 98
arm length measurements 108–109 factor) 432 Blackfeet Indians, markers of
arms race, evolutionary 310, 317, 408, behavior/behavioral variation 224
409, 469 ecology/evolutionary ecology 22 blank slate (tabula rasa) theory 551
aromatic hydrocarbons 574–575 evolution 278–279 blending theory of inheritance 48;
arousal levels 431; see also fight-or- flexibility 345 see also genetics
flight response, stress genetics 267, 270 blood–brain barrier 426, 427
artistic temperament, and mental impacts on health, cultural blood gases 182–183
disorder 552, 561 transitions 588 blood groups 238–239
arterial oxygen saturation 181–182 isolation 13 and disease associations 227–228
artificial formula feeding 588–589 neuroendocrine mechanisms Duffy system 232
AS (ankylosing spondylitis) 230 277–278; see also endocrinology, genetics 51
asexual reproduction 309–311 behavioral incompatibility selection 228–229
ASFR (age-specific fertility rate) 80, 381 The Bell Curve (Herrnstein and and malaria 477
Ashkenazi Jews 218 Murray) 273 markers 214, 215, 220–223, 224,
Asian populations, body mass index 164 Belmont Principles 146 225–226
assisted reproductive technology 316 Belmont Report 144, 147 Mendelian genetics 49–50
assortive mating 64–65 benign environments 539–540; MN 63, 66, 67–68
asthma 464, 493, 495, 496, 539 see also stress polymorphism 37
astrocyte-neuron-lactate shuttle Bergmann’s rule 36, 157, 166, 167, 222 race/typology 232, 233
428, 430 Berkeley growth study 95 soluble antigens 215–216
astrocytes 426, 429 The Blood Group Antigen Facts Book
asymmetry, fluctuating (FA) 110, 313, b-globin, DNA markers 255–256 (Reid and Lomas-Francis) 216
324–325; see also symmetry blood pressure, high see hypertension
atherosclerosis see cardiovascular BIA (bioelectrical impedence analysis) Blumenbach, Johann Friedrich 267
disease 116, 120 BMC (bone mineral content) 117, 119
attachment 302–303, 345, 384, 411, bi-acromial diameter 104–105 BMI see body mass index
417, 555–556; see also affection, Biblical theory of human BMR (basal metabolic rate) 122–123,
pair bonds biogeography 268 340, 360–361, 383, 520
606 Index
Boas, Franz 30–31 information processing 408, 434 cancer 493, 496; see also breast cancer,
Bod Pod® 116, 118–119 measuring procedures 425 skin cancer
body cell mass (BCM) 117, 118, 123 and metabolic syndrome 520, and calorie restriction 534
body composition studies 33, 116; 521–522, 522, 522–523, 524–525 causation 503, 506–510
see also anthropometry nonhuman primate studies 534 cervical 495, 503, 512
additional methods 120–121 and pair bonds 413 colon 200
anthropometry 117–118 recent human evolution 492 cultural transitions 585
bioelectrical impedence analysis 120 sleep 429–430 hormone-dependent 330, 332
compartmental models 117 specific brain regions 428–429 and infection 495
densitometry 118–119 stress response mechanisms 414 liver 503, 512
dual energy X-ray absorptiometry 119 substrate specificity 430 longevity/senescence 536–537
and energy metabolism 121–122 and vitamin D 200 lung cancer 498
hydrometry 119–120 Brazil, cultural transitions 592 ovarian 200
log-log regression 122–123 BRCA gene 509 and pollution 574–575
nutritional adaptation 37 breast cancer 200, 332, 511 prevention 493
weight adjustments 122 causation 503, 507–509, 508–509, 512 stomach 228
whole body potassium counting 118 discordance hypothesis 494 vaccines 495
body dysmorphic disorder (BDD) 110 genetics 509 vaginal 570
body fat see adipose tissue/adiposity growth/development 495 candidate genes 253, 255
body mass index (BMI) 116, 117, hormone levels 330 carbohydrate metabolism 430, 499, 499
158, 492 breast-feeding 40, 136, 342–343; carbonic anhydrase, markers of
effects of climate/nutrition 164–166, see also childcare, weaning variation 218
167, 168 behavioral impacts of change on cardiovascular disease (CVD) 41, 233,
fecundity 327 health 588 492, 493, 496, 511
figures/tables 159, 163, 165, 166 biomedical models of health 588–589 adiposity rebound 400
hypertension 497 brain development 431 causation 503, 504–506
insulin resistance 498 discordance hypothesis 494 gene–environment interactions
lactation 344 discussion points 346 518–519
body weight 122–123; see also surface and disease ecology 345 and infection 495, 504, 512
law, three quarter power function female behavior 287 life span approach 40–41
Bolivia 587 immune system 463, 521 thrifty phenotypes 24
bone milk composition 343–345 cardiovascular system 183, 282
growth/maintenance 200, 201, 204 and parental investment theory 296 caries, dental 496, 497–498
mineral content 117, 119 policy implications 345–346 carrier agents, hormones 127–128, 130
typing 232 reproductive suppression 328 carriers of disease, definition 468
borderline personality disorder 556 and skin coloration 204 Cartesian dualism 425
bottlenecks, developmental wet nursing 449 case studies, mental disorders 552,
520–521, 524 breast size, and fecundity 328–329 553, 555
bottlenecks, population 68, 529, breeding see cooperative breeding, castration studies 280
542–543 reproduction catch-up growth 396, 400
Bougainville study 223, 224 bride capture 444, 445 causal triangle model, chronic disease
Bowlby, John 555 bride service 444, 445 503–504; see also chronic disease
boys see juveniles/adolescents, males bride wealth 445–446; see also marriage causation
brain derived neurotrophic factor BSC (biological species concept) 12 cultural transitions 592
(BDNF) 432 bulimia nervosa 326; see also eating Hill’s criteria 567
brain development/growth 383 disorders pollution, environmental 571
adolescence 432–433 Burkitt’s lymphoma 506 primary/secondary causes 503–504;
childhood 431–432 bushmeat 473, 478 see also chronic disease, infectious
embodied capital 440 buttock circumference causation
infants 431 measurements 102 cell biology
pregnancy/lactation 339–340, 344 Bwa Mawego 405, 417 adhesion 507, 508–509
stress endocrinology 407 cell replicative ability 531–532
young adults 433 CAESAR (Civilian American and cycle arrest 507, 508–509
brain function 425–426, 433–434 European surface anthropometry death (apoptosis) 507, 508–509,
and age 520 resource) 110 529–530, 532–533
astrocyte-neuron-lactate shuttle 428 calcium, and skin coloration 204 longevity/senescence 535–537
discussion points 434 calibration, anthropometry 102 telomeres 532
energy metabolism 407, 426–427, callipers, skinfold 37–104 cellular-mediated immunity 463–464
429, 430–431 calorie restriction 326, 327, 534, 541 Center for the Study of Ethics in the
and embodied capital 440 calorimeters 113–114, 114–115 Professions 144
history of discipline 426 camouflage, and skin coloration 196–197 “central dogma” of biology 56
Index 607
centrosomes/centrioles 55 chronic mountain sickness (CMS) 172 competitor derogation 298

cephalic index 31 chronological aging 195 complement system 462
cerebral spinal fluid (CSF) 128 cigarette smoking 492, 493, 498, complementary feeding of infants 343
cerumen (ear wax) types 219 536–537, 585 complementary genes 314
cervical cancer 495, 503, 512 cirrhosis, liver 496 computerized tomography (CT)
CF (cystic fibrosis) 219–220, 273 Civil Rights movement 266 scanning 116, 121
challenge hypothesis 354 Civilian American and European confidentiality, research ethics 152
chance processes in evolution surface anthropometry resource conflicts of interest 153
see genetic drift (CAESAR) 110 conformity 555
change, defining 587; see also cultural civilizations, ancient see ancient Egypt/ conscious awareness 24.16, 407, 409
transitions, ecological change Mesopotamia, traditional human consent, informed 145–146, 150–153
character displacement 14 populations conservation of energy, law of 113
characteristic equation, Euler–Lotka 83 class differences 30 constant heat summation, law of 113
cheating behavior 22 classical markers of variation constitutional somatology 34
chemosensitivity 180–181 see markers of variation constrained down-regulation
childcare, co-operative 383–384, classifications, racial 30, 220–223, 271 hypothesis 328
385–386, 387–388, 389 climate; see also size/morphology, consumption through life course,
childhood; see also infancy effects of climate and nutrition embodied capital hypothesis
brain development 431–432 and body weight/proportions 442–443
evolution of 381–382, 385–386, 158–161, 162 contaminants, food 396, 397, 399;
409–410 change, and infectious disease 478 see also pollution
growth studies see anthropometry, and ear wax types 219 controlling mates 354
growth extremes, adaptation to 17 Coolidge effect 353
infections 496 Climatic Research Laboratory, co-operation, evolution of 11, 12, 22
and later ovarian function 325 Natick 36 co-operative breeding 384, 408, 443;
learning 386 clonal selection 463 see also reproduction
sensitivity to stress 406 closed calorimeters 114 evolution 383–384, 385–386,
chimpanzees see nonhuman primate clustering populations 268–269 387–388, 389
studies Coale–Demeny model life tables coronary atherosclerosis
Chinese farmers, age-specific 78–79, 80 see cardiovascular disease
fertility rate 381 coalescent theory 5 cortico-thalamic-striatal circuit 433
Chlamydophila pneumoniae 505, 511, 512 coalescent trees 245, 246, 248 corticotrophin-releasing hormone
cholera 227–228, 469, 510 Coale–Trussell model fertility (CRH) 338–339, 341
cholesterol 505, 536 schedules 81–83, 84 cortisol 127, 132, 136, 329;
chromatin 53 cocaine addiction 558 see also stress endocrinology
chromosomes 53–54, 574–575; codons 57 brain development, infant 431
see also genetics, mutations coercion, sexual 300, 301, 354 family environments 397, 416,
X chromosome 252–253, 280 coevolution, infectious disease 469 415–417
chronic disease, evolutionary cognitive behavioral therapy 329 pair bonds/parental care 282, 283, 412
perspective 491, 496, 500; cognitive diversity 270; stress response mechanisms 405,
see also discordance hypothesis see also behavior: genetics 414–415
dental caries 497–498 cognitive impairment, stress response cost-benefits
discussion points 501 mechanisms 414 adaptation 25
hypertension 496–497 Cohen priesthood 536 meiosis 309, 310
insulin resistance 498–500, 499, 500 cold injury hypothesis 198–199 courtship displays 352
lung cancer 498 Cold Spring Harbor Symposium on cousins, marriage between 54, 311–312
objections to evolutionary approach Quantitative Biology 34, 37 craniometric variation 31
491–493 cold stress adaptation 36 creativity, and mental disorder 552, 561
scope/nature 493 colon cancer 200 CRH (corticotrophin-releasing
chronic disease, infectious causation color-blindness 221 hormone) 338–339, 341
502, 511, 512–513 color-matching 194 Crohn’s disease 495
atherosclerosis 503, 504–506, 512 coloration, skin see skin coloration cross-sectional data cleaning 97–98
breast cancer 512 Common Rule 145 cryptic female choice 311, 316
cancer 503, 506–510 comparative genomics 205 cryptic ovulation 389, 410
causal triangle model 503–504 compartmental models of body CSF (cerebral spinal fluid) 128
discussion points 513 composition 117 CT (computerized tomography)
overview 502–504 compatible genes 312–313, 314, 317 scanning 116, 121
pre-eclampsia 511–512 compensation 147 culture/cultural influences
pregnancy sickness 510–511, 512 competition between pathogens 469 adaptation 20, 582–584
primary/secondary causes 503–504 competition for mates 353–354; behavior 278
schizophrenia 511, 512 see also mate choice brain evolution 409
608 Index
culture/cultural influences (cont.) quotation 0.1 demographic transition 450, 540, 581,
definitions 582 speciation in finches 13 589–590; see also cultural
female behavior across menstrual struggle for existence and transitions, epidemiology
cycle 285–286 adaptation 21 demography 74–75, 84, 88–89;
genetics of mate choice 316 Voyage of the Beagle 30 see also fertility, mortality rates
global distributions of human data discussion points 89–90
migration/gene flow 252–253 cleaning 97–98 Euler–Lotka characteristic equation
growth variation due to editing 97 83–85
environmental factors 396 security 152 exponential growth 75
human biology 35–36 sharing 147 fitness sensitivities/elasticities 87–88
and information processing 408 databases life tables 75–78, 78–80
longevity/senescence 542–543, 544 human mortality 78 and pollution, environmental 566
mate choice evolution 302–303 IMGT/HLA 229 population projection matrix
pair bonds/parental care 284 Dawkins, Richard 529 models 86–87
psychotherapy paradigm 560 DDT (dichlorodiphenyltrichloroethan) reproductive value 85–86
race/typology 266–267, 273 401 dendrites/dendritic spines 428, 461
skin coloration 204–205 defense mechanisms 460, 460 dendrograms 225, 226
cultural transitions 581, 582, definitions densitometry 118–119
586–587, 594 acclimatization 170 dental caries 496, 497–498
additive models 591, 592 acculturation 581 Department of Health and Human
behavioral impacts on health 588 adaptation 25, 170 Services (DHHS), US 145
change, defining/measuring 587 aging/senescence 528 Department of Health, Education and
child growth studies 584 anthropometry 92–93, 96–97 Welfare (DHEW), US 145
culture and adaptation 582–584 biocultural evolution 535 depression/mania 496
curvilinear models 591, 592–593 carriers of disease 468 adaptationist perspective 461
definitions/terminology 581 change 587 attachment theory 556
degenerative diseases 584–585 chronic disease 502 case study 554
demographic transition 589–590 cultural and economic transitions 581 cultural transitions 585
discussion points 594 culture 582 evolutionary psychiatry 553–554,
and economic transitions 584, developmental adaptation 170 553–554, 561
587, 588 developmental responses 170 and fatty acids 494
environmental impacts of endemic diseases 469 and loss 560
change 589 epidemics/epidemiology 469 psychotherapy paradigm 560
health care impacts of change genes 52–53 DES (diethylstilbestrol) 570
588–589 genetic adaptation 170 desert physiology study 33
heterogeneity models 591, 593 growth 379 design compromise, evolutionary
history of discipline 582 heritability 4 medicine 460–461
inconsistency models 591, 593–594 human biology 42 despotic males 446–447, 544
infectious/parasitic disease 585–586 incubation period 468 deterministic models 74
mental health/substance abuse 585 indigenous 170 development, social 409–410;
models 591–592 latency periods 468 see also growth
psychosocial stress 590–591 life history theory 528 developmental acclimation 19
regional focus 586–587 maximum reproductive developmental acclimatization 19
research directions 594 potential 529 developmental adaptation 19, 21, 23,
curvilinear models 591, 592–593 native 170 26; see also adaptation, altidudinal
CVD see cardiovascular disease natural selection 7 adaptation
CYP17 gene 330 parental investment theory 529 definition 170
cystic fibrosis (CF) 219–220, 273 pollution 567 epigenetics 24–25
cytokines 464, 522, 523 polymorphism 3 fetal 341
reproductive success 7 and mate choice 303
dairy foodstuffs 219 reservoirs of disease 468 pulmonary volumes 175, 176, 181, 182
dams 477 species 12 size/morphology 167
DARC (Duffy antigen receptor for zoonotic infections 468 stage of development 18
cytokines) 233 deforestation, and emerging thrifty genotypes 23–24
Darkness in El Dorado (Tierney) 145 diseases 477 developmental age 31
Darwin, Charles 9–10 degenerative diseases 20, 41, 584–585; developmental bottlenecks 520–521, 524
evolution of cooperation 22 see also chronic diseases developmental inertia 583;
evolutionary theory 15, 65 delusions 551, 553; see also imprinting
genetics 48, 50 see also schizophrenia/ developmental landmarks 390
longevity/senescence 528 schizotypal disorder developmental responses,
natural selection 68 demes 269 definition 170
Index 609
DHA (docosahexaenoic acid) 344 cultural transitions 594 dominant eigenvalues 86

DHEAS (dehydroepiandrosterone) demography 89–90 dominant genes 51, 63
131, 136, 405, 433 DNA markers 257 Dominican peoples, stress
DHEW (Department of Health, embodied capital 452 endocrinology 397, 416, 415–417
Education and Welfare), US 145 endocrinology 137–138, 287–288 dopamine 412, 413
DHHS (Department of Health and energy metabolism 123–124 dosage suppression 56
Human Services), US 145 ethics 148 dose–response relationships, organic
diabetes 41, 127, 233, 493, 496; evolutionary medicine 479 pollutants 573
see also insulin resistance, evolutionary psychiatry 561–562 doubly labeled water (DLW) 115
metabolic syndrome evolutionary theory 15 dreaming 429
adiposity rebound 400 genetics 71–72, 317 Drosophila spp. 14, 533–534, 540
autoimmune diseases 495 growth 392–393, 402 drug abuse 460–461, 496, 558, 585;
evolutionary medicine 461 history of human biology 42–43 see also substance abuse
gene–environment interactions longevity/senescence 545–546 DSM (Diagnostic and Statistical
518–519 male reproductive physiology Manual) 551
and pollution 573–574 364–365 dual energy X-ray absorptiometry
risk factors 493 markers of variation 234 (DXA) 117, 119
thrifty genotypes 23–24 mate choice 303–304, 317 dual photon absorptiometry 116
thrifty phenotypes 24 metabolic syndrome 525 dualism, Cartesian 425
Diagnostic and Statistical Manual ovarian function 332 Duffy blood group system 232, 233
(DSM) 551 pollution, environmental 575 Dunker isolates 67
diameters, measurement 104 pregnancy/lactation 346 DXA (dual energy X-ray
diarrhea 510 race/typology 274 absorptiometry) 117, 119
diet see digestive system, nutrition size/morphology, effects of climate/
diethylstilbestrol (DES) 570 nutrition 168 ear pinna measurements 109
differential parental investment 309, skin coloration 205–206 eating disorders 326, 399, 554, 555,
316; see also parental stress endocrinology 417 559, 588
investment theory disease; see also chronic disease, ecogeographic rules 222
diffusion limitation 173 immune-system, infectious disease ecological change, human-induced
digestive system; see also nutrition autoimmune 461, 463, 464, 467, 477, 478–479
and blood group 228 495, 540 ecology
gut morphology 538, 542 and blood groups 227–228 cultural transition models 592
Homininae evolution 520 degenerative 20, 41, 584–585 history of human biology 37–38
lactase 219, 491 endemic 469 and immunity 465–466, 466–467,
digit length ratio 325 and environmental hypoxia 172 467–468; see also evolutionary
dihydrotestosterone 131 and HLA systems 229–230, 233 medicine, immune system
dioxins see PAHs (polycyclic aromatic and lactation 345 of reproduction 40
hydrocarbons) markers of variation 233–234 of variation 338, 345
direct calorimetry 114–115 and mate choice 352 economic factors; see also cultural
directional asymmetry 110 prevention 450–451 transitions, embodied capital
directional selection 7, 8, 63, 68–69 and race/typology 273 and growth variation 396
discordance hypothesis 460, 491, 493, resistance to 474 and race/typology 272–273
500; see also thrifty genotypes and stress 413–414 economy of locomotion 177
breast cancer 507 disposable somas 528, 530–531 ECF/ECS (extra-cellular fluids/solids)
chronic disease 496, 502–503 disruptive/diversifying selection 8 117
culture and adaptation 583 diversity see markers of variation, EDB (“evo-devo”) 14
degenerative diseases 585 race/typology, variation educational level, and mate
evolutionary psychiatry 558–559, 561 division of labor 444, 451; attraction 352
growth/development 495 see also embodied capital, education-based capital 450, 451–452,
infection 494–495 extra-somatic wealth 451–452
and insulin resistance 499, 500 divorce 284, 301, 397, 416, 415–417; EEAT2 428, 431
nutrition 493–494 see also fathers (absent) effective size of populations 5, 63
physical exercize 494 DLW (doubly labeled water) 115 Egyptians, ancient 446
psychosocial factors 495–496, 591 DNA (deoxybribonucleic acid) 53 eigenvalues 86
reproduction 494 analysis, history of 38–39 eigenvectors 86
discussion points isolation methodology 58 El Niño Southern Oscillation effect 478
adaptation 26 markers see markers of variation elasticities, fitness 87–88
altidudinal adaptation 186 structure 51 elephants, alcohol use 558
anthropometry 110–111 docosahexaenoic acid (DHA) 344 embodied capital 386, 439
brain function and energetics 434 dominance, and competition for adaptation 452
chronic disease 501, 513 mates 353 adaptive complex 440–441
610 Index
embodied capital (cont.) thyroid hormones 134–135 Eskimo peoples 18, 497
brain as 440 time management 136 estradiol/estrogen 323–324
consumption/productivity through endurance performance 177 animal studies 278
life course 442–443 energy metabolism 113; see also body birth 131
discussion points 452 composition studies, nutrition body fat/fecundity 327
extra-somatic wealth 439, 443–444 and body composition/size 121–122 and breast cancer 507–508
foraging societies/nonhuman body fat/fecundity 327 childhood influences 325
primates 441, 441–442 body weight adjustments 122 energy metabolism 325–327
labor markets, skills-based 450–452 brain function 407, 426–427, 429, evolutionary endocrinology 127,
and life history theory 439–440 430–431 128, 131, 132
and life span 543 calorimetry, indirect/direct 114–115 fetal developmental influences
modern world 450 and development 358 324–325
premodern period 448–450 discussion points 123–124 genetic variation 329–331
sedentism/horticulture 444–445 doubly labelled water 115 hormone level correlates 331
tribal pastoralism 445–446 and embodied capital 440 hormone level norms 331–332
variation in male quality/marriage endocrinology 130, 134 hourglass figure 328–329
market 447–448 and fertility 40 menopause 127
empathy 407 heart rate/activity monitoring parental care 411–412
emphysema 496 115–116 and physical activity levels 327
encephalization 339–340, 534–535, history of discipline 113–114 population differences 322–323
542; see also brain development/ immune system 466, 521 and senescence in men 360
growth and infection 398 ethics 144–145, 151
ENCODE Project Consortium 53, 56 and lactation 344 bioethics 144–145
endemic diseases, definition 469 and metabolic syndrome 520, compensation 147
endocrine disruptors 355 521–522, 522, 522–523, 524–525 data sharing 147
endocrinology, behavioral 287; and ovarian function 323–324, discussion points 148
see also gender differences, 325–327 group consent 146–147
hormone levels, reproduction, plasticity, phenotypic 524–525 implementing ethical standards 148
stress endocrinology pregnancy 340–341 information resources 150, 151, 153
discussion points 287–288 reproductive suppression 327–328 informed consent 145–146, 150–153
endocrine mechanisms 279 sleep 429–430 and pollution, environmental 575
evolution of behavior 278–279 and sperm production 355 and research 150–153
female behavior across menstrual testosterone costs 360–361, risks/benefits, research 147, 152–153
cycle 284 361–362, 363 ethnicity see race/typology
pair bonds/parental care 281–283 environment ethological paradigm, evolutionary
sex differences in human behavior and genetics see gene–environment psychiatry 554–555, 560
281, 280–281 interactions euchromatin 53
testosterone levels in males 283–285 human-induced changes 477, eugenics 273; see also racism
theoretical frameworks 277–278 478–479 eukaryotes, post-transcriptional
endocrinology, evolutionary 127, 137 impacts of change on health 589; processing 50, 57
cortisol/stress 136 see also cultural transitions, Euler–Lotka characteristic equation
and development 357–359, 359 pollution 83–85
discussion points 137–138 stressful see stress eumelanin 59, 192–195
energy management 130 enzymes 130, 217, 218, 225–226 Europe and the People Without History
female reproductive function eosinophils 461 (Wolf) 269
132–133, 571–572 ephelides (freckles) 193–194 European populations, body mass
ghrelin/hunger 135–136 epidemics 469, 496 index 164
growth/organization 130–132 epidemiology 41, 362, 469, 474, 492; The Evolution of Man (Haeckel) 1
hormone form/function/assessment see also demography, mortality evolutionary demography 75
128–130 rates evolutionary developmental biology
hormone receptors 130 epigenetics see gene expression (EDB “evo-devo”) 14
insulin/energy sequestration 134 episodic memory 427 evolutionary medicine 459–461, 460,
leptin/fat 135 Epstein–Barr virus 506, 508–509, 511 479; see also chronic disease,
male reproductive function 133–134, equations immune system, infectious disease
572–573 Euler–Lotka 83–85 evolutionary psychiatry 551, 560–561
measuring procedures 127–128 fitness sensitivities/elasticities 87–88 adaptationist paradigm 551, 560
plasticity, phenotypic 137 Greville 76 anorexia nervosa 554
pollution, environmental 571 late-life stage 531 attachment theory 555–556
protein hormones 129–130 renewal 83 case study 552, 553, 554, 555
senescence 136–137 erection 356, 359 depression/mania 553–554, 556, 561
steroid hormones 128–129 erythropoietin 183 discussion points 561–562
Index 611
ethological paradigm 554–555, 560 sedentism/horticulture 444–445 fetuses/fetal; see also pregnancy
innate-module paradigm 556–558, social stratification/nation states/ development, and ovarian function
560–561 despots 446–447 324–325
mismatch paradigm 558–559, 561 tribal pastoralism 445–446 imprinting/programming 61, 324,
psychotherapy paradigm 559–560, variation in male quality/marriage 340, 568–571, 583
561 market 447–448 mortality, altidudinal adaptation 178
schizophrenia/schizotypal disorder extrinsic mortality factors 9 nutrition, role in metabolic
551–553, 555, 559, 561 eye color, inheritance 59 syndrome 523–524
evolutionary sources of variation origins hypothesis of adult disease 41
65–67 facial symmetry see symmetry and pollution, environmental
evolutionary stable strategies 10 false alarms 556 568–571
evolutionary theory 3; false belief tests 557 protection hypothesis 510–511, 512
see also adaptation, endocrinology, families; see also kin fever as defense mechanism 460
genetic drift, growth, Homininae, demographic transition 450, 540, FFAs see fatty acids
natural selection 581, 589–590; see also cultural FFM see free fat body mass
baby fat 520 transitions, epidemiology fidelity, sexual 353, 356
behavior 278–279 environments, stress endocrinology fight-or-flight response 556, 590;
brain growth/evolution 407 397, 416, 415–417 see also stress
childhood 409–410 evolution 409–410; filarial infections 467
components of fitness 9–10 see also embodied capital, finches, speciation 13
consequences of constrained mate extra-somatic wealth fire 542
choice 316–317 stress endocrinology 413–414 Fisher, Sir Ronald A. 59, 71
contemporary developments 15 studies, schizophrenia/schizotypal Fisherian traits 312
cooperation 11, 12, 22 disorder 552; see also twin studies fitness
cultural brain evolution 409 famine 519; see also nutrition behavioral evolutionary ecology 22
discussion points 15 fat mass (FM) 119; see also free fat components of 9–10
family evolution 409–410 body mass and demography 74
levels of selection 10–12 fat tissue see adipose tissue/adiposity sensitivities/elasticities 87–88
longevity/senescence 528–529, fathers, absent 301; see also divorce fixation, genetic 5
529–531, 535–537, 543–544 fatty acids 343, 344, 345, 494 flagging outliers 97–98
mate choice 295–296, 302–303 and life span 540 flagging variables 98
metabolic syndrome 522, 522–523 and metabolic syndrome 522, fluctuating asymmetry (FA) 110, 313,
micro to macroevolution 14–15 522, 523 324–325
modeling adaptation 10 fear responses 556, 590; see also stress FM (fat mass) 119; see also free fat
modes of selection 7–9 feces 128 body mass
neutral theory of molecular fecundity see fertility, reproduction fMRI studies 287, 412, 427
evolution 5–7 feedback loops, endocrine 279 folate/folic acid 197–198
origin of variation 3 females follicle stimulating hormone (FSH)
recent human evolution 491–492 adolescence in girls 390–391, 432 128, 129, 130, 131, 132
shifting balance theory 69, 71 behavior across menstrual cycle 284 male endocrinology/development 357
skin pigmentation 195, 198–204 demographic dominance 74 and senescence 137, 360
sociality, evolution of 406 in labor force 451 spermatogenesis/erectile function
speciation 12–14 reproductive endocrinology 132–133 355, 359
synthesis 3, 14 reproductive effort 351 food see breast-feeding, digestive
variation within populations 3–4, reproductive function and pollution system, nutrition
65–67 571–572 foraging societies 383, 384, 441;
excitement, stress endocrinology X chromosome 252–253, 280 see also Homininae, thrifty
415, 416 femur epicondyle measurements genotypes, traditional human
exercise see physical activity 107, 108 populations
expensive tissue hypothesis 426 fertility 39–41; see also reproduction adolescence 387–388
exponential growth 75 adaptive variations 362–363 chronic disease 497
external auditory meatus altidudinal adaptation 177–178 consumption/productivity 442–443
measurements 107 and body fat 327 embodied capital 441, 441–442
extinction 71 and demography 80–81 forensic evidence 232
extra-cellular fluids/solids hourglass figure 328–329 foresight 24.16, 407, 409
(ECF/ECS) 117 and mate choice 353 formula feeding 588–589
extrapair copulation 11 model fertility schedules 81–83 fossil record 14
extra-somatic wealth 439 and phytoestrogen consumption 331 founder-effect speciation 13, 67–68, 529
and adaptation 452 Princeton Indices 81 four compartment model of body
labor markets, skills-based 450–452 proximate determinants 83 composition 117
premodern period 448–450 and stress 329 four-field approach to race/typology 30
612 Index
frailty and inflammation 540 and pollution, environmental 569 mitosis 55

Frankfurt Agreement 94 post-transcriptional processing 57 modern synthesis 62, 65
Frankfurt plane measurements 107, 108 proteins 57 molecular 52
freckles 193–194 regulation of 56 non-Mendelian see gene expression
free fat body mass (FFM) 116 transcription 56, 57 online resources 72
bioelectrical impedence analysis 120 transgenerational 25 particulate theory of inheritance
body weight adjustments 122 translation 57 48–49
dual energy X-ray absorptiometry 119 variability 51 polygenic inheritance 58–59
four compartment model 117 gene flow 66–67, 70–71, 250–253, 474 polymerase chain reaction
hydrometry 119–120 gene trees 5 technique 58
log-log regression 122–123 geneological clusters, race/typology replication 54–55
three compartment model 117 268–269 sequencing methods 58
two compartment model 117 geneological trees 268 shifting balance theory 69, 71
free fatty acids see fatty acids genes 52–53 Genetics and The Races of Man
free living situation, energy genetic adaptation 20–21, 170, 176, (Boyd) 221
metabolism 114 184–185, 491; see also adaptation, The Genetics of Human Populations
free radicles 192, 198, 361, 461, 532; altidudinal adaptation (Cavalli-Sforza and Bodmer) 226
see also antioxidants genetic correlation 4 Genghis Kahn 544
frequency distributions 97 genetic diversity see markers of genoclines 222–223
frequency-dependent selection 8–9 variation, race/typology, variation Genographic Project 233
Freud, S. 560, 561 genetic drift 4–5, 55, 63, 67–68; genogroups 227
fruit and vegetables 493, 494, 497, 540 see also neutral theory of molecular genome-wide association (GWA) 185
FSH see follicle stimulating hormone evolution genomics, skin coloration 205
functional adaptation 19; and gene flow 70–71 genotoxicity, air pollution 574–575
see also adaptation, genetic HIV/AIDS 474 genotypes, thrifty see thrifty genotypes
adaptation longevity/senescence 529 geography
functional imaging studies 287, 412, 427 and selection 70 Biblical theory of human
genetic load 64 biogeography 268
G6PD (glucose-6-phosphate genetic markers see markers of human migration/gene flow 250–253
dehydrogenase) deficiency 218, variation and race/typology 267, 268, 270–271
231–232 genetic models 10 size/morphology, effects of climate/
GABA (gamma-butyric acid) 428, 431 genetic quality (good gene hypothesis) nutrition 163–164
Galen (Greek anatomist) 92 9, 11, 312–315 gestation see pregnancy
Galton, Sir Francis 59 “Genetic Structure of Human ghrelin 135–136
game theory 10 Populations” (Rosenberg et al.) 270 gingivitis 496
gametes 55 genetic variation see markers of girls see females, juveniles/adolescents
garlic 505–506 variation, race/typology, variation glabella measurements 107, 108
gastric ulcer 228, 503, 512 genetics 48, 71; global distributions see geography
gastrocnemius measurements 108 see also Hardy–Weinberg global warming 566; see also ecological
Gc (group specific component) 217 equilibrium, mate choice genetics, change, pollution, environmental
gender differences 29; see also females, population genetics, selection globalization 581; see also cultural
males atherosclerosis 504 transitions
climatic influences on body weight/ behavior 267, 270 glucose, role in brain function 426;
proportions 158, 159–161, 163 chromosome architecture 53–54 see also nutrition
endocrinology, behavioral 281, chronic disease 493 glucose-6-phosphate dehydrogenase
280–281 discussion points 71–72 (G6PD) deficiency 218, 231–232
longevity/senescence 544 DNA isolation methodology 58 glutamate cycling 426, 427
skin coloration 204 DNA/RNA 53 anterior cingulate cortex 429
telomere shortening 532 evolutionary sources of variation astrocyte-neuron-lactate shuttle 428
gene chips 242 65–67 hippocampus 428–429
gene–environment interaction 59–60, heredity and environment 59–60 plasticity, phenotypic 432, 433
60–61 history of human biology 37, 38–39 glutamate dehydrogenase gene
atherosclerosis 504–505 HIV/AIDS 474 (GLUD) 428
chronic disease 502, 503 human modes of inheritance 49, glutamate exotoxicity 431
mental disorders 551, 552 50–52 gluteal fold measurements 108
metabolic syndrome 518–519 immune system 463, 464–465 glycemic index 500
ovarian function 331 longevity/senescence 535–537 glycogen stores, brain 427, 429–430
and plasticity, phenotypic 524 malaria 476–477 Gm (immunoglobulin) 217, 220
gene expression, phenotypic 24–25, meiosis 55–56 gold standard methods
56, 61 Mendelian 49–50 anthropometry 117
longevity/senescence 536–537 microevolution 65, 70–71 calorimetry 115
Index 613
gonadotropin-releasing hormone Hadza people 128, 387–388, 441, hemolytic disease of the newborn
(GnRH) 131–132, 357–358 441–442, 497 (HDN) 229
gonadotropins see follicle-stimulating hairlessness in humans 195 hepatis B virus 41
hormone, luteinizing hormone hallucinations 551, 553; heritability; see also genetics
good gene hypothesis 9, 11, 312–315 see also schizophrenia/schizotypal definition 4
Gould, Stephen Jay 12 disorder mate choice 301–302
gradual evolution/gradualism 14 Hamilton’s rule 11 heroin addiction 558
grandparents 408, 409–410, 543–544 haplotypes 230, 254 Hess’s law of constant heat
Graves’s disease 127, 134 haptoglobins 217, 233 summation 113
gray matter 432 Hardy–Weinberg (H-W) equilibrium heterochromatin 53
great depression 32 4, 7, 50, 62–63 heterochrony 385
greenhouse gases 478; effective size of populations 63 heterogeneity models of cultural
see also ecological change, microevolution of allele frequency transition 591, 593
pollution, environmental change 65 heteroplasmy 52
Greville equation 76 microevolutionary process heterozygous advantage 7
group behavior, ethological interactions 70–71 hexosaminidase A (HEXA) deficiency
paradigm 555 random mating 63 218–219
group consent, ethics 146–147 random mating departures 63–65 HGDP (human genome diversity
group selection 12, 22, 469, 529 sickle cell hemoglobin/malarial project) 39, 233, 269
group specific component (Gc) 217 resistance 230 HGP (human genome project) 39,
group splitting catalysts 552–553 test 70 52–53, 243, 536
growth 32–33, 379–380; harems 445, 447; see also reproductive HIF-1 (hypoxia inducible factor)
see also anthropometry, childhood, strategies system 184, 185–186
infancy, juveniles/adolescents, life Harpenden anthropometer 106 high altitude hypoxia see altidudinal
history theory, size/morphology Harpenden growth study 95 adaptation
anthropometry 96–97 Harpenden infant measuring table 102 Hill’s criteria of causation 567
Boas, Franz 31 Harpenden infantometer 102 Himalayan peoples
childcare, co-operative 383–384, Harpenden neonatometer 101–102 altidudinal adaptation 170
385–386, 387–388, 389 Harpenden skinfold calliper 37–104 fertility/fecundity 177–178
discussion points 392–393, 402 Harpenden stadiometer 101 native endurance performance 177
and cultural transitions 584 Harpenden supine measuring table 102 pulmonary volumes 175
discordance hypothesis 495 Harrison, Geoffrey A. 37 hip circumference/girth
and endocrinology 130–132, Harvard growth study 95 measurements 102
357–359, 359 HB (Human Biology) Journal 31–32, 41 hippocampus 136, 414, 426, 427,
environmental hypoxia 171 HBA (Human Biology Association) 41 428–429
history of human biology 40–41 HDN (hemolytic disease of the Hispanic race/culture 266, 271
life history theory 384–385 newborn) 229 historical civilizations see ancient
nutritional adaptation 37 head form/cephalic index 31 Egypt/Mesopotamia, traditional
pelvic growth in females 388–389 health 41 human populations
pollution, environmental 571 and birth weight 341 historical perspectives 29
reproduction 380–382 and skin coloration 204–205 adaptation/ecology/international
sexual development 389–390 span 528 programs 37–38
span 528 stress endocrinology 417 biomedical anthropology/health/
UK 95 health care services, impacts of change epidemiology 41
US 95 on health 588–589 Boas, Franz 30–31
variation due to environmental hearing loss, high frequency 496 brain function and energetics 426
factors 396, 397, 401–402 heart disease see cardiovascular disease cultural transitions 582
weaning/early childhood 381–382 heart rate monitoring 115–116 definition 42
growth faltering 397, 398, 399 heat shock proteins 462 discussion points 42–43
stress response mechanisms heat stress adaptation 36 DNA analysis/molecular genetics
399, 414 height measurement 99–100 38–39
trade-offs with immunity 466–467 Helicobacter pylori 228, 469, 510–511, 512 energy metabolism 113–114
growth hormone (GH) 130, 132 Helmholtz, Herman 113 extra-somatic wealth 439, 443–444
guidelines, research ethics 150–153 hemoglobins human biology societies/journals
gum disease 496 concentration 183–184 41–42
gut morphology 538, 542 DNA markers 255–256 infectious disease, evolutionary
GWA (genome-wide association) 185 and malaria 477 perspective 468
markers of variation 215, 216 literacy/numeracy 439
habitat fragmentation 477; oxygen affinity 183 post-mid-twentieth century 36–37
see also ecological change oxygen diffusion curve 173, 174 post-war/mid-twentieth century,
habituation 19 polymorphism 7 US/UK 33–36
614 Index
historical perspectives (cont.) hormone proliferation hypothesis, hypothyroidism 134

pre-WWII/population biology 31–33 breast cancer 507–508 hypoxia , 171–172; see also altidudinal
race/typology 29–30, 271–272 hormone receptors 130 adaptation
reproduction/growth studies 39–41 horticultural societies 444–445, 449; acclimatization to 174–175
WWII 33 see also agricultural societies, brain 429
HIV/AIDS 41, 233 traditional human populations growth variation due to
and breastfeeding 589 host-pathogen interactions 310, 313, environmental factors 396, 397
immune system function 398 317; see also infectious disease infancy/early childhood growth 399
infectious disease 472–474 hourglass figure 328–329 juvenile/adolescent growth 401
juvenile/adolescent growth 401 Hox gene 14 hypoxia inducible factor (HIF-1)
and poverty 398–399 HPA see hypothalamus-pituitary- system 184, 185–186
Hiwi peoples 441, 441–442 adrenal axis
HLA (human leukocyte antigen) HPV (human papillomavirus) 504, 507, IAHB (International Association of
systems 65, 215, 216, 220, 508–509, 511 Human Biologists) 41
229–230, 233 human adaptability project 146, 224 IBP see International Biological
Holtain (Tanner–Whitehouse) skinfold Human Biology Association (HBA) 41 Program
calliper 104 Human Biology (HB) Journal 31–32, 41 Iceland, human migration/gene flow 252
homeostasis 17–18; see also stress human biology societies/journals ICSU (International Council of
Homininae 203, 249–250, 380; 41–42 Scientific Unions) 37–38
see also agricultural societies, human genome diversity project IGF (insulin-like growth factor) 130, 132
foraging societies, horticultural (HGDP) 39, 233, 269 iliac crest measurements 106, 107, 108
societies, thrifty genotypes, human genome project (HGP) 39, imagination 407, 409
traditional human populations 52–53, 243, 536 IMGT/HLA Database 229
adolescence, reason for evolution 392 human leukocyte antigen (HLA) 65, imitation 408
Australopithecines 426 215, 216, 220, 229–230, 233 immediate pigment darkening
baby fat 520 human mortality database 78 (IPD) 194
brain function and energetics 426 human papillomavirus (HPV) 504, 507, immortal genomes 530–531
brain growth/evolution 407 508–509, 511 immune system 461;
childhood evolution 385 human remains 146–147 see also autoimmune diseases,
developmental landmarks 390 humeral epicondyle measurements evolutionary medicine, infectious
diet 538 107, 108 disease
digestion 520 hunger 135–136 adaptive immunity 462–463
famine 519 hunter-gatherers see foraging societies, antibody-mediated immunity 463
indigenous populations 170, 581 Homininae, traditional human breastmilk antibodies 343, 345
industrial societies 364 populations cellular-mediated immunity 463–464
infectious disease, evolutionary Huntington’s disease 51 comparative aspects 464–465
perspective 469 Hutterite community 65, 81, 381 discussion points 479
juvenile/infant dependence 407 Huxley, Julian 267 ecological/evolutionary immunity
modern human origins 245–250 H-W equilibrium see Hardy–Weinberg 465–466
muscle/fat ratios 499 equilibrium energy metabolism 521
Neanderthal man 203, 249–250 hydrometry 119–120 evolutionary medicine 461
recent human evolution 491–492 hygiene hypothesis 495 immunity as evolved reaction
homosexuality 297 hypertension 41, 492, 496 norm 466
horizontal gene transfer 50 adiposity rebound 400 innate immunity 461–462
hormonal priming 131 chronic disease, evolutionary juvenile/adolescent growth 401
Hormonally Active Agents in the perspective 496–497 mate choice 467–468
Environment (US Research psychosocial stress 591 and schizophrenia/schizotypal
Council) 575 and race/typology 273 disorder 554
hormone levels 128, 322–323, thrifty phenotypes 24 and skin coloration 197
323–324; see also endocrinology, hyperventilation 174 and stress 413–414
ovarian function, testosterone hypoglycemia 429 trade-offs 466–467
correlates 331 hypogonadism/hypogonadotropism and undernutrition 398, 399
environment-gene interactions 331 467 and vitamin D 200
fetal developmental influences hypomania see depression/mania immunoglobulins 217, 256
324–325 hypothalamus 134, 135 immunological hypothesis, blood
norms 331–332 hypothalamus-pituitary-adrenal (HPA) groups 228
population differences 322–323, axis 279, 357, 359, 414 immunosuppression 351, 361–362,
323–324 impacts of change on health 590 508–509
steroids 128–129, 352 neuroendocrinology of affection 411 Imperial units 93
hormone mimics 570, 571–572; pair bonds/parental care 282, 412 imprinting, fetal 61, 324, 340, 568–571,
see also pollution stress response mechanisms 414–415 583
Index 615
in vivo neutron activation analysis mate choice 310 International Council of Scientific
(IVAA) 121 pregnancy sickness 510–511 Unions (ICSU) 37–38
inbreeding 64, 311–312 and sedentism/agricultural international programs, human
Inca peoples 446, 447 societies 581 biology 37–38
incest 312; see also inbreeding and sexual reproduction 351 International Studies of Circumpolar
income/education- based capital 450, sexually transmitted 352 Peoples 38
451–452, 451–452 and skin coloration 197 intersexual selection see mate choice
incompatibility selection, blood group and stress 413–414 intrasexual competition 353
markers 228–229 testosterone level variations 363–364 intrasexual selection 310
incomplete penetrance, genetics 51 tuberculosis 471–472 intraspecific studies see animal studies,
inconsistency models, cultural and undernutrition 398, 399 nonhuman primate studies
transitions 591, 593–594 virulence/antibiotic resistance intrauterine environment 341;
incubation period, definition 468 469–471 see also fetuses, pregnancy
Indians, American 497 inference see theory of mind intrinsic brain activity 427
indigenous, definition 170; infertility, male 198 intrinsic rates of increase 83
see also traditional human inflammation 464, 467, 523, 539, 540, 543 intrinsic senescence 9
populations influenza 479 introgression, genome 13
indirect calorimetry 115 information processing 408, 434; Inuit peoples 164, 167, 586–587
individual differences see variation see also brain function Inupiat Eskimos, markers of
individual selection 7 information resources, demographic variation 224
industrial pollution see pollution 74–75; see also websites investing reproductive strategy 302
industrial societies, testosterone levels informed consent 145–146, 150–153 iodine 135
in males 364 inguinal crease measurements 108 IPD (immediate pigment darkening) 194
infancy 397, 401–402; inheritance; see also genetics IRB (Institutional Review Board)
see also childhood human modes of 49, 50–52 144, 145
altitude 399 non-Mendelian 61 iron binding proteins 462
brain development 431 particulate theory of 48–49 iron deficiency 398
contaminants, food 399 polygenic 58–59 isolated populations 12–13, 251, 269
discussion points 402 innate behavior 440 isotopes of oxygen 115
formula feeding 588–589 innate immunity 461–462 IVAA (in vivo neutron activation
infection and undernutrition 398, 399 innate-module paradigm, evolutionary analysis) 121
poverty 398–399 psychiatry 556–558, 560–561
stress, psychological 399 Institutional Review Board (IRB) journals, human biology 41–42
infant measuring tables, Harpenden 102 144, 145 Jung, C. G. 560
infanticide 11, 354, 410 insulin 127 junk DNA 6, 50, 254
infantometers, Harpenden 102 insulin resistance 492, 498–500, 518, juveniles/adolescents 397, 400,
infectious disease 460, 468–469; 520; see also diabetes, metabolic 401–402; see also puberty
see also evolutionary medicine, syndrome altitude 401
immune system as brain protection strategy 522–523 as apprenticeship 387
accommodation 20 endocrinology 134 in boys 391–392, 432
acute disease 503 figures/tables 499, 500 brain development 431–432, 432–433
atherosclerosis 495, 504 life history theory 521–522, 522 diet 400–401
and cancer 495, 506–510 risk factors 493, 498 discussion points 402
and chronic disease 493, 503–504; insulin-like growth factor (IGF) 130, 132 evolutionary theory 379, 385,
see also chronic disease, infectious insulinotropic foodstuffs 500 386–387, 392
causation intelligence, and mate attraction 352 in girls 390–391, 432
coevolution 469 interdemic (group) selection 12, 22, infection 401
and cultural transitions 585–586 469, 529 life history theory 384
discordance hypothesis 494–495 interferon 462 natural selection for 387–388
discussion points 479 intergenerational inertia 583; pollution, environmental 401
emerging diseases 477–479 see also transgenerational factors sexual selection 388
energy metabolism 521 International Association of Human stress endocrinology 407
epidemics 496 Biologists (IAHB) 41
growth variation due to 396, 397 International Biological Program (IBP) Kalahari bushmen 497
hemoglobins 217 96, 582, 38 Kalahari Research Group 38
HIV/AIDS 472–474 cultural transitions 586 karyotype 49, 50
host-pathogen interactions 310, and ethics 147, 148 keratinocytes 193, 201
313, 317 human adaptability project 146, 224 ketones 427, 430, 431
impacts of change on health 589 International Children’s Centre kibbutz, Israeli 312
juvenile/adolescent growth 401 Coordinated Longitudinal Growth kin/kinship 279, 386; see also families,
malaria 474–477 Studies 95 twin studies
616 Index
kin/kinship (cont.) life expectancy 492 evolution 440–441, 528–529, 543–544

altruism, ethological paradigm 555 life history theory 40–41, 88, 316; fitness sensitivities/elasticities 87
evolution 409–410; see also longevity/senescence, and growth/development 495
see also embodied capital, reproductive strategies humans 535
extra-somatic wealth childhood 409–410 inflammation/frailty 540
recognition 356, 406 chronic disease 503 life history traits, human
selection 11, 278, 470 in context of pregnancy/lactation 537–538, 544
!Kung hunter gatherers 81, 84 see breast feeding, pregnancy life span/reproduction 538–539
adolescence, natural selection for definition 528 male reproductive physiology
387–388 and demography 74 359–360
age-specific fertility rate 381 ecological/evolutionary immunity modern synthesis 531
life history theory 441, 441–442 465–466 niches, human 541, 544
marriage 389 and embodied capital hypothesis plasticity, phenotypic 538, 541–542
survivorship 79 439–440 telomeres 54, 532
Kuru 41 energy metabolism 425 longitudinal data cleaning 97–98
kinship 279, 386 foraging societies/nonhuman longitudinal studies, anthropometry 95
primates 441, 441–442 loss, and depression 560
labor markets, skills-based 450–452 growth, evolution of 384–385 loss of function (LOF) mutation 57
lactase digestion 491 human traits 538 Lotka equation 83–85
lactase deficiency markers 219 immunity as evolved reaction norm 466 love, biology of 287, 411;
lactate 184, 427, 428, 430, 431 insulin resistance 521–522, 522 see also attachment,
lactation see breast-feeding and mate choice 302 endocrinology, pair bonds
lactoferrin 462 longevity/senescence 528–529, 535, low back pain 496
lactose intolerance 496 537–538, 544 lung cancer 498
Lamarck, Jean-Baptiste 49 reproductive ecology, male 362–363 luteinizing hormone (LH) 128, 129,
Lamarkian inheritance 61 lifelong demographic heterogeneity 533 130, 131, 132
Lange calliper 104 life span 538–539; see also longevity/ male endocrinology/development 357
language 392, 407–408, 409–410, 556 senescence and senescence 137, 360
Lasker, Gabriel W. 35 lifestyles, Western 493, 592; Lyme disease 478
late-life stage 531, 540; see also aging, see also cultural transitions, lymphocytes 462–463
longevity/senescence discordance hypothesis
latency periods, definition 468 life tables 75–78 MaB (Man and the Biosphere Program)
Latin America, cultural transitions 587 model 78–80 38, 586
latitude, and skin coloration 195 light skin coloration, evolution of macro to microevolution 14–15
law of conservation of energy 113 198–204 macrophages 461
law of constant heat summation 113 linkage disequilibrium 4, 249 Madagascar 87
LCPUFA (long-chain polyunsaturated Linnaeus, C. 265, 267 magical thinking 551;
fatty acids) 343, 344 literacy, history of 439 see also schizophrenia/schizotypal
lead pollution 399, 568 liver cancer 503, 512 disorder
endocrinology 571 LOF (loss of function) mutation 57 magnetic resonance imaging (MRI)
environmental impacts of change on log-log regression, body composition/ 116, 121
health 589 size 122–123 major histocompatibility complex
prenatal growth/fetal long-chain polyunsaturated fatty acids (MHC) 216, 309, 314–315, 316,
programming 570 (LCPUFA) 343, 344 317, 463
sperm counts/spermatogenesis 573 longevity/senescence 528, 540–541, Makiritare peoples 224
learning, childhood 386 544–545; see also aging, late-life malaria 469, 470, 583
legumes stage, menopause cultural transitions 586
blood group antigens 215 age-specific gene action/pleiotropy DNA markers 255–256
Mendelian genetics 48–50 529–530 evolutionary perspective 474–477
length measurement, animal studies 533–535, 538, and genetic selection 69
supine/recumbent 101 540–541, 543, 545 history of human biology 37
leprosy 398 apoptosis 532–533 immune system function 398
leptin 127, 130, 131, 135 benign environments 539–540 and poverty 398–399
Leslie matrix 86, 87, 89 cell biology/genetics 535–537 resistance 230–231, 231–232, 233
leukemia 461, 495 cell replicative ability 531–532 males 351, 357
Lewontin, R. C. 266, 270 cultural influences 542–543, 544 competition for mates 281, 353–354
Lexis diagrams 76 definitions/terminology 528–535 controlling mates/coercion 354
Leydig cells 359, 363 discussion points 545–546 discussion points 364–365
LH see luteinizing hormone disposable somas/immortal genomes endocrinology/development
libido, male 134, 355–356 530–531 357–359, 359
life events 414 endocrinology 136–137 erection 356
Index 617
infertility, and folate levels 198 malarial resistance, other markers good/compatible genes 312–315
libido 355–356 231–232 inbreeding/inbreeding depression
life history theory 362–363 methodological advances/polymerase 311–312
male reproductive effort 351–352 chain reaction 240–241 sexual selection/reproduction 309–311
mate choice 352–353 modern human origins 245–250 mate poaching 298
mate seeking/attraction 352 natural selection 226–227, 253–256 mate seeking vs. parenting 136
paternal behavior 356–357 phenylalanine hydroxlase maternal depletion syndrome 328;
paternal care in multimale groups deficiency 219 see also oocyte depletion
406–407 population relationships/history 233 mathematical models, altruism 22
quality/marriagiability 447–448; population studies/ mating, random 63–65
see also despotic males microevolutionary processes MATLAB software 89
reproductive ecology 364 223–226 matrix models, population projection
reproductive effort 351–352 practical applications 232 86–87
reproductive endocrinology 133–134 PTC tasting 220 maximum reproductive potential
reproductive function, and pollution recent human evolution 492 (MRP) 529
572–573 serum proteins 216 Mayan peoples 445, 497
senescence 359–360 sickle cell hemoglobin/malarial MCIR (melanocortin 1 receptor) gene
sperm 354–355 resistance 230–231 locus 195, 202–203
spermatogenesis/erectile function 359 soluble antigens 215–216 measles, and immune system
testosterone level variations 363–364 transferrin 218 function 398
testosterone negative costs 351, 352, types 241–243 The Measurement of Human Growth
360–362 market integration 581 (Cameron) 96
Y chromosomes 247–248, 248, marriage 64, 386, 389, 391, 447–448; measures of central tendency 97
252–253, 280 see also mate choice, monogamy, measuring procedures, anthropometric
malformations, prenatal 569 reproductive strategies 98–99
malleoli measurements 107, 108 Mars climate orbiter 93 medial malleolus measurements
mammalian genetics 52 Martin anthropometer 105 107, 108
Man and the Biosphere Program (MaB) Masai people 497 Medical College Admission Test
38, 586 mass media influences on health 588 (MCAT) 329
mania see depression/mania Massachusetts Quartermaster Corps medicine see chronic disease,
Manual of Physical Anthropology Climatic Research Laboratory 36 evolutionary medicine, immune
(Comas) 29 mastoid process measurements system, infectious disease
maps, synthetic 225 107, 108 meiosis 55–56, 309, 310
markers of variation 214–215, mate choice 295, 299, 303, 352–353; melanin 59, 192–195
238–240, 256; see also blood see also marriage, monogamy, melanoma 193, 194, 196; see also skin
groups, variation reproductive strategies cancer
albumins 216–217 attachment theory 302–303 memory 282, 427
apportionment of human variation discussion points 303–304 menarche
256–257 ecological/evolutionary immunity developmental landmarks 390
carbonic anhydrase 218 467–468 fetal developmental influences 324
cerumen (ear wax) types 219 evolution of cultural differences pelvic growth in females 388–389
choice of 244 302–303 pollution, environmental 571–572
cystic fibrosis 219–220 evolutionary theory 295–296 sexual selection for 388
discussion points 234, 257 individual differences between men Mendel, George 48–49
disease associations 233–234 299–301 Mendelian genetics 49–50, 59
enzymes 217, 218 individual differences between menopause 41, 137, 352
genetic diversity assessment 244–245 women 301–302 and breast cancer 508
global distributions of human male reproductive physiology 352 endocrinology 133
migration/gene flow 250–253 monogamy/long-term mating estrogens 127
glucose-6-phosphate dehydrogenase 297–298 fetal developmental influences 324
deficiency 218 parental investment theory 296–297 life history traits 544
group specific component 217 promiscuity/short-term mating and wealth/resources 539
haptoglobins 217 298–299 menstrual cycle 132–133, 323–324;
hemoglobins 215, 216 sex ratios 302 see also ovarian function
hexosaminidase A deficiency sexual strategies theory 297 and energy metabolism 325–327
218–219 mate choice genetics 309, 310, 317 female behavior across 284
HLA systems 65, 215, 216, 220, consequences of free mate choice population differences in hormone
229–230, 233 316–317 levels 322–323
human genome regions 243 differential parental investment mental disorders, and cultural
immunoglobulins 217 309, 316 transitions 585;
lactase deficiency 219 discussion points 317 see also evolutionary psychiatry
618 Index
Mesopotamia 446 mirror neurons 557–558 and pollution, environmental 574

messenger RNA 56 mismatch hypothesis see discordance pre/postnatal 178
metabolic regulation 134–135 hypothesis mosaic evolution 14
metabolic syndrome 20, 134, 161; mitochondria, genetics 51–52, 243 mouse mammary tumor virus (MMTV)
see also adipose tissue, diabetes, mitochondrial Eve 5, 39, 245, 246, 248; 508–509, 511
insulin resistance, metabolic see also out of Africa hypothesis MRI (magnetic resonance imaging)
syndrome, thrifty genotypes mitosis 53, 55 116, 121
as brain protection strategy 522–523 MMTV (mouse mammary tumor virus) MRP (maximum reproductive
developmental bottlenecks 508–509, 511 potential) 529
520–521, 524 MN blood group 63, 66, 67–68 Müllerian inhibiting hormone (MIH)
discussion points 525 MNLS (minimum necessary life 131, 280, 357
as life history strategy 521–522, 522 span) 537 Muller’s ratchet 310
longevity/senescence 536–537 model fertility schedules 81–83 multidisciplinary research 38
plasticity, phenotypic 524–525 model life tables 78–80 multifactorial inheritance see polygenic
prenatal nutrition, role 523–524 modern human origins 245–250 inheritance
thrifty phenotypes 24, 519, 520, 583 modern synthesis 62, 65 multigenerational factors 25, 408,
metastasis, cancer cells 507 modernization/modern world 581; 409–410, 417, 538, 583
methylation 24–25, 56, 61; see also gene see also cultural transitions, multilevel selection 22
expression discordance hypothesis multimodel distributions 247
metric system of measurement 93 embodied capital 450 multiple sclerosis 461, 495
Mexican Indian peoples 165 gradients 586 multiregional continuity model
Mexico, cultural transitions 592 lifestyles 493, 592 245–250
MHC (major histocompatibility psychosocial stress 591 muscle structure/metabolism 184
complex) 216, 309, 314–315, 316, modes of selection 7–9 muscle/fat ratios 499
317, 463 molecular adaptation 253 musical ability 61
mice, t gene locus 11; see also animal molecular clocks 6 mutation 65–66
studies molecular evolution, neutral theory air pollution 574–575
microcephalin gene locus 249 of 5–7 evolution of light skin coloration 199
microevolutionary processes molecular genetics genetics of mate choice 310
allele frequency change 65 definition 52 longevity/senescence 529–530
Australian Aboriginals 233 DNA isolation methodology 58 loss of function 57
interacting 70–71 genes 52–53 as origin of variation 3
markers of variation 222, history of human biology 38–39 and selection, 70
223–226, 227 polymerase chain reaction and sexual reproduction 317
micro to macroevolution 14–15 technique 58 variance 8
race/typology 269 sequencing: Sanger method 58 Mycobacterium spp. 471–472, 503
shifting balance theory 69, 71 sequencing: shotgun 58 myopia 496
microsatellite DNA regions 242–243, monogamy 297–298; see also marriage,
247–248, 249, 251 mate choice, reproductive NAGPRA (Native American Graves and
mid-point of arm measurements strategies Repatriation Act) 147
108–109 individual differences between men Natick Climatic Research Laboratory 36
mid-axillary line measurements 108 299–301 nation states/despots, extra-somatic
mid-inguinal point measurements 108 individual differences between wealth 446–447
migration women 301–302 National Center for Biotechnology
cultural transitions 592 mate choice 295–296 Information (NCBI) website 214
gene flow 66–67 and sex ratios 302 National Commission for the
global distributions 250–253 monogeism 29 Protection of Human Subjects of
and schizophrenia/schizotypal mood states Biomedical and Behavioral
disorder 559 adaptationist perspective 461 Research 144
and skin coloration 204 innate-module paradigm 556–557 National Research Act 144
studies 31, 33 morality 409 National Science Foundation (NSF) 147
MIH (Müllerian inhibiting hormone) morphological environmental effects Native American Graves and
131, 280, 357 see size/morphology Repatriation Act (NAGPRA) 147
military personnel 33 morphological symmetry see symmetry native, definition 170;
milk mortality rates; see also epidemiology see also traditional human
artificial formula 588–589 and disease prevention 450–451 populations
composition 343–345; human mortality database 78 natural fertility 81; see also fertility,
see also breastfeeding inbreeding/inbreeding depression reproduction
minimum necessary life span 311–312 Natural History, General and Particular
(MNLS) 537 males 360 (Buffon) 267
Minnesota semi-starvation study 33 and mate choice 302, 303 natural killer cells 461
Index 619
natural resources, environmental neural plasticity 428; see also glutamate paternal care in multimale
impacts of change on health 589 cycling groups 406
natural selection 68; see also evolution, neural tube defects (NTDs) 197–198 population growth 75
sexual selection, variation neuroendocrine responses pregnancy/lactation 338–339,
and adaptation 21, 462–463 see endocrinology, stress 342–343
adiposity 521 endocrinology sexual development 389–390
adolescence 379, 387–388 neuronal-lactate shuttle 428, 430 sperm competition 353
altidudinal adaptation 170, 185 neurons, energy storage 429 testosterone levels in males 364
balancing selection 69–70 neuroplasticity see plasticity, time management 136
and culture 583 phenotypic total fertility rate 380–381
definition 7 neurotransmitters 428 non-Mendelian inheritance 61
and demography 89 dopamine 412, 413 norms, hormone levels 331–332
directional selection 63, 68–69 and drug abuse 558 norms of reaction 4
and DNA markers 253–256 GABA 428, 431 Norway 78
evolution of light skin coloration 199 neutral DNA markers 238, 251, 254; NRR (net reproduction ratio) 80, 84
genetic drift 70 see also markers of variation NSF (National Science Foundation) 147
genetic markers 226–227 neutral theory of molecular evolution NTDs (neural tube defects) 197–198
group selection 12, 22, 469, 529 3, 5–7; see also genetic drift nuclear genome 243; see also human
growth 379 New World 39, 203–204, 225–226 genome project
HIV/AIDS 474 niches, human 541, 544 nucleotide diversity 245
infectious disease 462–463, 469, 474 Nipah virus 478–479 Nucleotide Sequence Database 147
levels of 10–12, 22 NMDA (N-methyl-d-aspartate) numeracy, history of 439
longevity/senescence 529–530, receptors 428 Nuremberg Code 144, 145
543–544, 545 noise pollution 568, 570 nutrition 167; see also breast feeding,
metabolic syndrome 524–525 Nomina Anatomica 92 digestive system, energy
modes of selection 7–9 noncoding regions 6, 50, 254 metabolism, size/morphology,
and mutation 70 nonhuman primate studies; stress
and pollution, environmental see also animal studies, embodied adaptation 37
566–567 capital hypothesis and atherosclerosis 504–505
pregnancy sickness 510 adolescence, natural selection for brain function and energetics 426
pregnancy/lactation 338–339 387–388 contaminants, food 396, 397, 399;
schizophrenia/schizotypal disorder age-specific fertility rate 381 see also pollution
552; see also adaptationist alcohol use 558 and development 358
paradigm altruism 22 discordance hypothesis 493–494
skin coloration 195–198 attachment theory 555 foraging societies/nonhuman
and skin coloration 205 behavioral evolutionary ecology 22 primates 442
social selection 409 blood groups 227 and growth variation 396, 397,
stabilizing selection 8 brain growth 383 400–401
thrifty genotype hypothesis 520 consumption/productivity through and immune system 464, 466
Y chromosome studies 248 life course 442–443 and infection 398, 399
nature nurture issue developmental landmarks 390 longevity/senescence 536–537,
see gene–environment interaction DNA markers 253, 254, 257 542–543
nausea 460, 510–511, 512 embodied capital 441, 441–442 metabolic syndrome 523–524
Nazi ideology 265, 273; see also racism genetic variation 272 and ovarian function 325
NCBI (National Center for growth 379–380, 380–382 plasticity, phenotypic 538
Biotechnology Information) HIV/AIDS 473 prenatal 523–524
website 214 immune system, evolutionary and prostate cancer 362
Neanderthal man 203, 249–250; perspective 465, 468 testosterone level variations 363
see also Homininae intraspecific variation, nutritional status assessment
Neel, James 146 endocrinology 135 standards, anthropometric 167
neodarwinian theory 3, 14, 62 infant care 383
neonatometers, Harpenden 101–102 kin recognition 356 obesity 23, 41, 161, 492, 496;
neotony 385 leptin structure/function 135 see also adipose tissue, insulin
Nepal 591 longevity/senescence 137, 359, resistance, metabolic syndrome,
nested family social structures 534–535, 537 nutrition
409–410, 445; see also families, mate choice 352 and body mass index 166
kin/kinship milk composition 343 degenerative diseases 585
net maternity rate 84 mirror neurons 557–558 developmental bottlenecks 520
net reproduction ratio (NRR) 80, 84 neural plasticity 428 effects of climate/nutrition 167
neural correlates of love 287; pair bonds 410 and fecundity 327, 328–329
see also endocrinology, behavioral pair bonds/parental care 281 and hypertension 497
620 Index
obesity (cont.) stress see hypoxia pastoral societies 445–446;

and insulin resistance 498 oxygen transport 180 see also agricultural societies
Pima Indian people 23–24 altidudinal adaptation 172–174, 179 patella measurements 107, 109
and pollution, environmental arterial oxygen saturation 181–182 paternal behavior 356–357, 406–407,
573–574 blood gases/direct measures of 412–413, 560
and socioeconomic status 396 pulmonary gas exchange 182–183 pathogen-host interactions 310, 313,
object-relations theory 560 cardiovascular system 183 317; see also infectious disease
occiput measurements 107, 109 hemoglobin concentration 183–184 PBBs (polybrominated biphenyls) 401
odor, human uses of 312, 314–315, 353 hemoglobin-oxygen affinity 183 PCBs (polychlorinated biphenyls) 401
oestrogen see estradiol/estrogen muscle structure/metabolism 184 PCR (polymerase chain reaction)
offsetting impacts of pollution 567 pulmonary ventilation during technique 58, 240–241
Okazaki fragments 54 exercise 181 Pea Pod® 116
Old Order Amish 64 pulmonary volumes 175, 176, 181, 182 pear-shaped bodies 499
Old Order Dunkers 67 resting ventilation 180 Pearl, Raymond 31–32
olecranon measurements 107, 109 ventilatory control/chemosensitivity peas, Mendelian genetics 48–50
omega 3/6 fatty acids see fatty acids 180–181 pelvic growth in females 388–389
one gene one enzyme hypothesis 52 oxytocin (OT) 127, 279 penicillin 470
one-sex deterministic models 74 interventions based on 287 penis 295
online resources see websites neuroendocrinology of affection 411 peptic ulcer 228, 503, 512
oocyte depletion 537, 544 pair bonds/parental care 281–282, period central death rates 76
open calorimeters 114 411–412, 413 peripatric speciation 13, 67–68, 529
opportunistic reproductive strategy 302 paternal care 412–413 peripheral vascular disease 496
optimism/pessimism 556–557 persistent organic pollutants see POPs
optimization 10 Pacific Islands 252, 581 personality disorder 556
organizational effects, sex differences PAH (phenylalanine hydroxlase) pessimism/optimism 556–557
in behavior 280 deficiency 219 pH, body 494
origins of replication 4.43 PAHs (polycyclic aromatic phenotype matching 356
osteoporosis 494, 496 hydrocarbons) 574–575 phenotypes, thrifty 24, 519, 520, 583;
OT see oxytocin pair bonds, human 279 see also gene expression
Our Stolen Future (Colborn, endocrinology 281–283, 413 phenotypic inertia 582
Dumanoski and Myers) 575 paternal care in multimale groups phenotypic variation 4
out of Africa hypothesis 39, 245–250; 406–407 phenylalanine hydroxlase (PAH)
see also mitochondrial Eve and social development 410 deficiency 219
outliers, data 97–98 pairwise mismatch distributions 247 phenylketonuria (PKU) 61
ovarian cancer 200 Paleo-Indians 146–147 phenylthiocarbamide (PTC) 220, 221
ovarian function; see also fertility, pangenesis 49 Philippines, cultural transitions 592
hormone levels, menstrual cycle, PAP (pulmonary artery pressure) 183 phototype classification 194
reproduction Papua New Guinea 586 phthalates 568, 573
body fat/fecundity 327 parapatric populations 13 phylogenetic species concept (PSC) 12
childhood influences 325 parasitism see infection/infectious phylogenetic trees 225, 226
discussion points 332 disease physical activity
energy metabolism 323–324, 325–327 parent–offspring conflict 12, 133, 310 altidudinal adaptation 172, 175–177
environment–gene interactions 331 in pregnancy 338, 339, 340, 341–342 discordance hypothesis 494
fetal developmental influences parental care and environmental hypoxia 172
324–325 endocrinology, behavioral 281–283 and estradiol 327
genetic variation 329–331 neuroendocrine responses to social and hypertension 497
hourglass figure 328–329 environment 411–412 mate seeking/attraction 352
oocyte depletion 537, 544 vs. mate seeking 136 monitoring 115–116
reproductive suppression 323–324, parental investment theory 296–297 and ovarian function 325–327
327–328 altricial offspring 538 pulmonary ventilation during 181
stress/fecundity 329 definition 529 and sperm production 355
suppression 323–324, 327–328 differential 309, 316 testosterone level variations 363
synchronised ovulation 354 and mate choice 300, 302 physical anthropology 29, 32, 221
overzealous response hypothesis 510 nonhuman primate studies 534 cultural transitions 582
ovulation, cryptic 389, 410 senescence - historical models 529 post-war/mid twentieth century 33–36
Oxford Child Health Survey 95 Parkinsonian dementia 41 and race/typology 265, 269
oxygen particulate theory of inheritance physiological age 31
isotopes 115 48–49; see also genetics phytochemicals 493, 494
radicles 192, 198, 361, 461, 532; particulates, pollution 568 phytoestrogens 331
see also antioxidants parturition 131, 133, 407; see also birth pigmentation, skin 195
saturation, arterial 181–182 weight Pima Indian peoples 23–24, 518
Index 621
pinna of ear measurements 109 and sperm production 355 effective size of populations 63
PKU (phenylketonuria) 61 variation in succeptibility 575 markers of variation 226–227
placenta 178, 463 polybrominated biphenyls (PBBs) 401 microevolution of allele frequency
plague 474 polychlorinated biphenyls (PCBs) change 65
Plasmodium spp. 474–477, 506 399, 569 microevolutionary process
plasticity, phenotypic 15, 128, 338; and diabetes/obesity 573–574 interactions 70–71
see also catch-up growth endocrinology 571–572 and race/typology 269
and adaptation 18, 23 environmental impacts of change on random mating 63
adipose storage 520 health 589 random mating departures
adolescence 432 genetic variation in succeptibility 575 63–65
brain function 425, 426–427, 428, juvenile/adolescent growth 401 population/s
430, 433 sperm counts/spermatogenesis biology 31–33
childhood 432 572–573 bottlenecks 68, 529, 542–543
and culture 583, 584 polycyclic aromatic hydrocarbons global 20; see also demographic
diet 538 (PAHs) 574–575 transition
and environmental stress 582 polygeism 29 hormone level differences 322–323,
hormones 128, 130, 137 polygenic inheritance 58–59 323–324
immune system 466, 467 polygenic variation 4 increases, historical 448
and information processing 408 polygyny 295; see also despotic males markers of variation 223–226
longevity/senescence 538, 541–542 competition for mates 353 mutation parameter/rate 244
metabolic syndrome 524–525 harem 445, 447 projection 75, 86–87
prenatal 61, 340, 523–524, individual differences between men and race/typology 233, 269–270
568–571, 583 299–300 selection see group selection
racial 30, 31 mate choice 302 Porphyromonas gingivalis 511–512
stress endocrinology 406 premodern period 448 postnatal
synaptic connections/plasticity 428 resource defense 447 behavior in females 287
play, rough-and-tumble 281 sedentism/horticulture 444 depression 553
pleiotropy 4, 59, 529–530 testosterone 284 mortality 178
plow/plough, invention 447 variation in male quality/marriage postzygotic barriers 12
pneumonia 398 market 447–448 potassium 116, 117, 118
Polish women 324, 326–327, 326 polymerase chain reaction (PCR) poverty, and growth 396, 398–399
political construct, race/typology as technique 58, 240–241 Prader–Willi syndrome 61
271–272, 272–273 polymorphism; see also single nucleotide precision, definition 96
political despots, and extra-somatic polymorphisms, variation predation, and life span 540
wealth 446–447 blood groups 227–228, 228–229 predictive adaptive response
political–economic factors, cultural definition 3 hypothesis 324;
transitions 582 DNA markers 244 see also imprinting, fetal
pollution, environmental 20, 569, hemoglobin 7 pre-eclampsia 511–512
575, 589 HLA systems 229–230 pregnancy 133, 338, 340–342;
air pollution 568, 570, 572, 574–575, immune system genes 464–465 see also breastfeeding, fertility,
574–575 and malaria 476–477 reproduction
anthropological study 566–567 markers of variation 226 adolescent 388
diabetes/obesity 573–574 and neutral theory of molecular assisted reproductive
discussion points 575 evolution 6 technology 316
endocrinology 571 restriction fragment length 225, breast cancer 507–508
environmental impacts of change on 241–242, 243, 245, 246, 257 discussion points 346
health 589 variation within groups 270 fat storage/brain growth 339–340
female reproductive function 571–572 Polynesia 591 female behavior 286–287
genotoxicity 574–575 polyploidy 13 gestation length 537
growth variation due to polytypy 270 and life span 539
environmental factors 396, 397 ponderal index 324 policy implications 345–346
hormone-like effects 25 POPs (persistent organic pollutants) preterm delivery 341
juvenile/adolescent growth 401 567–568 primate reproductive strategy
male reproductive function 572–573 and diabetes/obesity 573–574 338–339, 342–343
nature of industrial pollutants endocrinology 571–572 reproductive suppression 328
567–568 prenatal growth/fetal programming sickness 460, 510–511, 512
prenatal growth/fetal programming 570 and skin coloration 204
568–571 sperm counts/spermatogenesis prenatal period see fetuses
prereproductive mortality 574 572–573 preprogrammed behavior 440
research methodology 567 population genetics 62–63; prestige see status/prestige
research problems/limitations 566 see also genetics, selection prezygotic barriers 12
622 Index
primary causes, chronic disease psychotic symptoms 551; random mating 63–65
503–504; see also chronic disease, see also schizophrenia/schizotypal random genetic changes see genetic drift
infectious causation disorder random walks 5
primates see nonhuman primates PTC (phenylthiocarbamide) 220, 221 range, data 97
Princeton Indices, fertility 81 PTEN gene 509 rape 300, 301, 354
principle of allocation 9 puberty 131–132, 133, 280, 358–359; rapid replacement model
principle of autonomy 145 see also juveniles/adolescents see mitochondrial Eve
principle of independent assortment brain function/energetics 432 rates of change 584; see also cultural
48, 49–50 delayed 414 transitions
principle of segregation 49–50 fetal developmental influences 324 reaction norms, immunity as 466
probable mutation effect 199 life history theory 384 reactive oxygen species 192, 198, 361,
productivity pollution, environmental 571 461, 532; see also antioxidants
embodied capital hypothesis 442–443 public display, female behavior 285 reading/writing 558
labor markets, skills-based 450–452 Pueblo Indians 40 recessive genes 51
progesterone 133, 323–324 pulmonary artery pressure (PAP) 183 reciprocal altruism 11, 278
aggression 281 pulmonary gas exchange, direct recombination 50, 55–56
birth 131 measures 182–183 recumbent length measurement 101
breast cancer 507–508 pulmonary ventilation (VE) 172, 181 red blood cell markers, identifying 215
childhood influences 325 pulmonary volumes 175, 176, 181, 182 Red Queen hypothesis 310, 469
energy metabolism 325–327 purebred humans 269 referrals, ethics 147
fetal developmental influences purifying selection 7, 201, 204, 205 reflectance spectrophotometry 194
324–325 pyroxidine deficiency, and infection 398 reinforcement, reproductive isolation 14
hourglass figure 328–329 relational life tables 79–80
parental care 411–412 quantitative inheritance 58–59 relationships, stress endocrinology 417;
population differences in hormone quantitative trait loci (QTL) analysis 59 see also families, psychosocial
levels 322–323 Quechua people 167, 170, 181, factors, stress
programming, fetal 61, 324, 340, 184–185, 224 relative sitting height see RSH
568–571, 583 quinquennia 76 reliability, anthropometry 96–97
prolactin 133, 279 religious isolates 67
pair bonds/parental care 281–282, rabies 469 REM sleep 429
283, 411–412 race/typology 227, 265–266, 271, 273; renewal equation 83
and paternal behavior 357 see also skin coloration repetitive hyperinsulinemia
plasticity, phenotypic 137 blood groups 220–223, 232 499–500, 500
proliferation, cell 507, 508–509 classifications 30 replication, genetics 54–55
promiscuity/short-term mating clustering populations 268–269 reproduction; see also fertility,
298–299 continuous biological variation 267 hormone levels, ovarian function,
individual differences between men cultural distinctions 266–267 pregnancy
299–301 cultural transitions 582 altidudinal adaptation 172, 174
individual differences between discussion points 274 birth weight 178, 179
women 301–302 DNA markers 244–245, 256 discordance hypothesis 494
mate choice 295–296 genetic variation 226–227, 272 growth, evolution of 380–382
and sex ratios 302 geography 270–271 history of human biology 39–40
propensity state antedating language in history of 29–30, 271–272 life history theory 362–363
communication (PSALIC) 553 human genome diversity project 39 and life span 539
prostate cancer 200, 351, 362, 461 pollution, environmental 567 male 364
proteasome 537 population genetics 269 maternal oxygen transport 179
proteins population relationships/history 233 placenta 178
deficiency, and infection 398 populations as constructions 269–270 pre/postnatal mortality 178
gene expression, phenotypic 57 recent human evolution 491–492 and skin coloration 204
hormones 129–130 social/political/economic testosterone level variations 363–364
serum markers of variation 216, 217 constructions 272–273 reproductive isolating barriers
proximate determinants 89 variation within groups 270 (RIBs) 12, 13
disease 502, 503 The Races of Europe (Coon) 30, 267 reproductive isolation (RI) 12–13,
fertility 83 racism 265, 272, 273; see also Nazi 251, 269
PSALIC (propensity state antedating ideology reproductive strategies 352;
language in communication) 553 radial styloid measurements 107, 109 see also mate choice, monogamy,
PSC (phylogenetic species concept) 12 radioactivity 498 promiscuity/short-term mating
psychoactive drugs 460–461 radius measurements 107, 108 demographic transition 450
psychosocial factors see social radix 77 despotic males 446–447
perspectives, stress radon 498 and extra-somatic wealth 446
psychotherapy 559–560, 561 ragged distributions 247 genetics of mate choice 310
Index 623
modern world 450 sample size 97 sexual conflict 10, 11

premodern period 448–450 sampling error 5 sexual development, humans/
primate 338–339 San Juan Pueblo Indians 40 chimpanzees 389–390;
short/long-term trade-offs 340 Sanger method, sequencing 58 see also juveniles/adolescents,
trade-offs with immunity 467 sarcasm 409 puberty
variation in male quality/marriage SARS (severe acute respiratory sexual dimorphism, skin coloration 204
market 447–448 syndrome) 478 sexual reproduction, evolution of
reproductive success 7, 324–325; scale of being 29 309–311, 317, 351; see also fertility,
see also fertility scapula measurements 107, 109 reproduction
reproductive suppression 323–324, schistosomiasis 465, 467, 586 sexual selection 9–10
327–328 schizophrenia/schizotypal disorder 511 adolescence 379, 387, 388, 392
reproductive value 85–86 case study 552, 553 behavioral evolutionary ecology 22
research 150–153 causation 503 brain growth/evolution 407
research methodology, environmental evolutionary psychiatry 551–553, 561 good/compatible genes 312–315
pollution 566, 567 and group behavior 555 mate choice 302, 310–311, 317
reservoirs of disease, definition 468 infectious causation 511, 512 monogamy/long-term mating 298
resistance to disease 474; migration 559 parental investment theory 296
see also evolutionary medicine, mismatch paradigm 559 promiscuity/short-term mating
immune system, infectious disease seasonality in growth 400 298–299
resource-based mate choice 297–298 secondary causes, chronic disease skin coloration 204
resource defense polygyny 445, 447 503–504; see also chronic disease, sexual strategies theory (SST) 297;
resting metabolic rate (RMR) 122–123, infectious causation see also reproductive strategies
340, 360–361, 383, 520 secular trend in growth 31, 161–164, SHBG (sex hormone binding
resting ventilation 180 396–397 globulin) 128, 130
restriction fragment length sedentism 444–445, 581; shifting balance theory 69, 71
polymorphisms (RFLPs) 225, see also agricultural societies short tandem repeat loci (STRs)
241–242, 243, 245, 246, 257 segregationism 273 242, 243
rhesus (Rh) blood groups 229; seizures, infant 431 short-term mating see promiscuity/
see also blood groups selection see natural selection, sexual short-term mating
rheumatoid arthritis 461 selection shotgun sequencing 58
RI (reproductive isolation) 12–13, selectively neutral mutations 3, 5–7; SI units 93
251, 269 see also genetic drift sickle-cell hemoglobin 7, 41, 496
RIBs (reproductive isolating barriers) self-awareness 407, 409 blood group markers in classification
12, 13 self-esteem, and mate choice 300 of race 221
rickets 200, 201, 204 selfish genes 529 blood polymorphism 37
risk factors, chronic disease 493 semen displacement 295 cystic fibrosis markers 220
risks/benefits, research 147, 152–153 semi-conservative base pairs 54 history of human biology 37
risk-taking, and testosterone 461 semispecies 13; see also speciation malaria 230–231, 255, 476–477
RMR (resting metabolic rate) 122–123, semi-starvation study 33; pleiotropy 59
340, 360–361, 383, 520 see also calorie restriction recent human evolution 491
RNA 53, 56 senescent span 528; see also aging, late- signaling, depression/mania 553
Rochester Desert unit 33 life stage, longevity/senescence Silent Spring (Carson) 575
rodents, t gene locus 11; see also animal sensitive information, data security 152 simple sequence repeat loci
studies sensitivities, fitness 87–88 (SSRs) 242
rough-and-tumble play 281 sensitivity to stress 406, 416 single nucleotide polymorphisms
RSH (relative sitting height) 159, 163 sequencing, gene 52–53, 58 (SNPs) 242, 244, 254
and body mass index (BMI) 158, 161, serial founder effect model 251 size/morphology, effects of climate and
164–166 serum 25(OH) D 200 nutrition 157–158, 159, 166–167,
effects of climate/nutrition serum proteins 216–217, 225–226 167–168; see also body mass index,
167, 168 severe acute respirator syndrome growth
runaway sexual selection 10 (SARS) 478 body weight/proportions 158–161, 162
sex allocation theory 316 discussion points 168
saliva 128, 415 sex chromosomes 247–248, 248, global distributions 163–164
Salmonella typhi 469 252–253, 280 sampling/methodology 158
saltatory growth 40 sex differences in human behavior secular trend in body weight/
SAM (sympathetic adrenal medullary see gender differences proportion 161–164
system) 414, 590 sex hormone binding globulin (SHBG) skewness, data 97
Samoan Studies Project 165, 586 128, 130 skills-based labor markets 450–452
cultural transitions 591, 593 sex ratios, and mate choice 302 skin cancer 193, 203, 205, 511
psychosocial stress 591 sex-specific gene flow 252–253 causation 504, 507
status inconsistency models 594 sexual coercion 300, 301, 354 melanoma 193, 194, 196
624 Index
skin coloration 192, 205; see also race/ South Pacific Islands 518 accommodation 20
typology Soviet Union, alcohol abuse 588 adaptation 25
and cancer 504, 507 speciation 12–14 benign environments 539–540
in classification of race 222 species, definition 12 cultural transitions 582
discussion points 205–206 species selection 12, 22, 469, 529 and cultural/technological
evolution of light color 198–204 sperm/ spermatogenesis 134, adaptation 20
evolution of skin pigmentation 195 354–355, 359 fecundity 329
and health in modern humans competition 10, 353 genetic adaptation 21
204–205 counts 353, 355 growth variation due to 166, 396,
melanin 192–195 and pollution, environmental 397, 399
natural selection 195–198, 199 572–573 and habituation 19
sexual dimorphism 204 spina bifida 198 heat/cold stress 36
skinfold callipers 37–104 spinal muscular atrophy (SMA) 57 homeostasis 17–18
skinfold measurements 97, 103, 104 sports participation 325–327, 352; hypobaric hypoxia 171
skull vertex measurements 107, 109 see also physical activity mate choice 302–303
skydiving 363 SSHB (Society for the Study of Human military personnel 33
SLC24A5 gene locus 203 Biology) 41 pregnancy 341, 345
sleep 429–430 SSRs (simple sequence repeat loci) 242 schizophrenia/schizotypal
SMA (spinal muscular atrophy) 57 SST (sexual strategies theory) 297; disorder 552
smallpox 227–228, 474 see also reproductive strategies testosterone level variations 363
smoke detector metaphor 556 stabilizing selection 8 stress endocrinology 136, 405, 406,
smoking 492, 493, 498, 536–537, 585 stable equivalent population 84 417, 590–591; see also cortisol,
SNPs (single nucleotide stable population models 75, 83 endocrinology
polymorphisms) 242, 244, 254 stadiometers 100–101 brain growth/evolution 407, 409
social perspectives 411, 414; staff training, anthropometry 99 child sensitivity to 406, 416
see also stress standard deviation checks 97–98 discussion points 417
anxiety 559 standard deviation of differences family environments 397, 416,
capital 591 (SD) 96, 97 415–417
cognitive research 560 standard error of measurement family evolution 409–410
constructs, race/typology as 272–273 (Smeas) 96 fight-or-flight response 556, 590
Darwinism 273 standards information processing 408
deficit models of mental disorders 558 anthropometric 167 juvenile/infant dependence 407
degenerative disease 585 ethical 148 kinship 408
development 358 starvation, Minnesota study 33; neuroendocrinology of affection 411
discordance hypothesis 495–496 see also calorie restriction oxytocin 282
family evolution 409–410 statins 505 pair bonds 413
growth variation due to stationary populations 83 parental care 411–412
environmental factors 396 statistical clustering of populations 269 paternal care 406–407, 412–413
human biology 35–36 statistics, use of 32 social environmental responses 411
impacts of change on health 590–591 stature measurement 99–100 social mind/family 413–414
memory 282 status/prestige social selection 409
mind 413–414 cultural transitions 591, 593–594 sociality, evolution of 406
neuroendocrine responses 411 extra-somatic wealth 446–447 stress response mechanisms 136,
scenario building 407, 409 mate choice 300, 303 414–415, 590–591
selection 409 psychosocial stress 591 strokes 496; see also cardiovascular
stratification, and extra-somatic stepfathers 301 disease
wealth 446–447 sternum measurements 107, 109 structural reduction hypothesis 199
status/prestige 591 steroid hormones 128–129, 352; Structure computer program 270
threat detection, innate-module see also endocrinology, hormone struggle for existence 21;
paradigm 556 levels, ovarian function, see also natural selection
sociality, evolution of 406, 407–408 testosterone subscapular skinfold measurements
societies/journals, human biology 41–42 stigma, and ethics 147 103, 104
Society for the Study of Human stochastic models 74 subspecies 267
Biology (SSHB) 41 stomach 228, 503, 512 substance abuse 460–461, 496, 558,
socioeconomic status 396, 451 STRs (short tandem repeat loci) 242, 243 585; see also alcohol use/abuse,
sodium intake, and hypertension 497 strategic pluralism theory 300 drug abuse
soft tissue measurements, stratum corneum 195 sugar consumption 497–498
anthropometry 97, 103, 104 stress, environmental 168; suicide 585
solar lentigenes (freckles) 193–194 see also cultural transitions, social Sultan of Morocco 351
Solomon Islands 146, 223, 224, perspectives sun reactive type classification 194
497, 586 acclimatization 19 sunburn 194, 196
Index 625
supine length measurement 101 differential parental investment 316 TOM see theory of mind
supine measuring tables, Harpenden 102 evolution of behavior 278 tooth decay 496, 497–498
surface area/mass ratio 157, 158, evolutionary medicine 461 total body electrical conductivity
159, 161, 163; see also size/ hormonal priming 131 (TOBEC) 121
morphology immune system 467, 468 total body potassium (TBK) 116,
surface landmarks, anthropometry interventions based on 287, 361 117, 118
106–110 libido 355–356 total body water (TBW) 117,
surface law 121–122 mate choice 136, 300–301 119–120
survivorship 67, 68, 77, 79 negative costs 351, 352, total fertility rate (TFR) 80, 380–381
sweat glands 195 360–362 Toxoplasma gondii 511
sweet peas, Mendelian genetics 48–50 other metabolic functions 137 toxoplasmosis 467
symmetry/asymmetry 110, 285 pair bonds/parental care 136, trade-offs
fluctuating asymmetry 110, 313, 283–285, 413 disposable somas/immortal genomes
324–325 paternal behavior 357, 412 530–531
and mate choice 300, 301, 303, 468 replacement therapy 361 immunity 466–467
sympathetic adrenal medullary system senescence 137, 360 prenatal growth/fetal
(SAM) 414, 590 sex differences in human programming 569
sympatric speciation 13 behavior 280 traditional human populations 41, 170,
synapses sperm production 355, 359 581; see also agricultural societies,
plasticity 428 stress endocrinology 405 foraging societies, Homininae,
pruning 432 variation 363–364 horticultural societies, thrifty
synaptophysin 428 TFR (total fertility rate) 80, 380–381 genotypes
synchronised ovulation 354 thalassemia 231–232, 233 acculturative stress model 585
synthetic maps 225 theory of mind (TOM) 407–408, 417 altidudinal adaptation 172,
innate-module paradigm 557–558 175–177
T cells 462–463, 463–464 social selection 409 ancient Egypt/Mesopotamia 446
t gene locus 11 thermogenesis in pregnancy 340 chronic disease, evolutionary
Tanner, James M. 32, 37 threat detection, innate-module perspective 500
Tanner–Whitehouse skinfold paradigm 556 dental caries 497–498
calliper 104 three-compartment model of body despotic males 446–447
tanning response 194–195 composition 117 endurance performance 177
tape measures 102–103 three-dimensional photonic images extra-somatic wealth 446–447,
Tay–Sachs disease 218, 220, 492 (3DPS) 121 448–450
TBK (total body potassium) 116, three-quarter power function 122 fire 542
117, 118 thrifty genotypes 23–24, 519, growth/development 495
TBW (total body water) 117, 119–120 518–520; see also metabolic life span 538–539
technical error of measurement (TEM) syndrome nutrition 493–494
96, 106, 106 insulin/energy sequestration 134 physical exercize 494
technology metabolic syndrome 524–525 psychosocial factors 495–496
adaptation 20 pregnancy 340 population increases 448
advances, anthropometry 110 prenatal nutrition, role 524 senescence 545
television, impact on health 588 thrifty phenotypes 24, 519, 520, 583 tribal pastoralism 445–446
telomerase 507, 508–509 thyroid function 220, 426 variation in male quality/marriage
telomeres 54, 532 thyroid hormone 127, 130, 131, 132, market 447–448
TEM (technical error of measurement) 134–135 training, anthropometry staff 99
96, 106, 106 Tibetan plateau 177, 178, 179, 200; traits, human evolutionary 406
temperature and body mass 157–158; see also altidudinal adaptation brain growth/evolution 407
see also size/morphology, time management 136 cryptic ovulation 410
thermogenesis time to the most recent common juvenile/infant dependence 407
tempo of growth 31 ancestor (TMRCA) 245 kinship 408
Terminologia Anatomica 93 Tinbergen, Niko 405 transcranial magnetic stimulation
terminology see definitions tissue typing 232 (TMS) 557
testosterone 127, 128, 131; Title 45 Public Welfare, Code of Federal transcription, genes 56, 57;
see also androgens, males, steroid Regulations, Part 46) 145(45 CFR see also gene expression
hormones Part 150 transferrin 218, 462
adaptive mechanisms 364 TMS (transcranial magnetic transformational grid, growth/
aggression 281, 353–354 stimulation) 557 reproduction 380
animal studies 278 Toba people 136 transgenerational factors 25, 408,
brain function 432, 433 tobacco smoking 492, 493, 498, 409–410, 417, 538, 583
competition for mates 353 536–537, 585 transitions see cultural transitions,
development 357–358 Tokelau Islands Study 586 demographic transition
626 Index
translation, genes 57; see also gene UVR (ultraviolet radiation) 192, 195, Viagra 356
expression 197–198, 199–202; see also skin Vibrio cholerae 510
transsexuals 281 coloration Viking Fund Summer Seminars in
trapezius measurements 109 Physical Anthropology 34
trauma VA (alveolar ventilation) 172 violence, endocrinology of 281, 283,
brain development, infant 431 vaccines 470, 494, 495, 512 353–354, 461
family environments 397, 416, vaginal cancer 570 virulence, infectious disease
415–417 validity, definition 96 469–471, 494
treatment, disease 494; Van Luschen scale 194 viruses, and cancer 507;
see also antibiotic medication variance see also infectious disease
trees, geneological/phylogenetic 225, data 97 visceral fat see abdominal fat
226, 268, 269 genetic 5 vitamins 493; see also antioxidants
coalescent tree 245, 246, 248 mutational 8 A 398, 399
Tregs (induced regulatory variation 266; see also evolutionary B group 197–198, 344
T cells) 464 theory, gender differences, gene D 132, 199–202, 204, 205
triangle model, chronic disease expression, markers of variation, vole species, pair bonds 413
503–504; see also chronic disease natural selection, plasticity, Voyage of the Beagle (Darwin) 30
tribal pastoralism 445–446; polymorphism, race/typology, Vytorin 505
see also agricultural societies size/morphology
triceps measurements 109 and adaptation 21 wager, life span 539
triceps skinfold measurements 103 apportionment of 256–257 waist-to-hip ratio (WHR) 328–329
Tristan da Cunha 68, 70 continuous biological Wales, markers of variation 224
trochanter measurements 107, 109 variation 267 warfare 444, 445, 446–447
trust, oxytocin levels 282 and culture 583 Washburn, Sherwood L. 33–34
trypanosomiasis 398 describing see anthropometry Watson and Crick 54
tuberculosis 219, 471–472, 503 ecological 338, 345 Watson strand 57
cultural transitions 586 evolutionary sources 3–4, 65–67 weak Garden of Eden model 247
cystic fibrosis markers 220 fecundity 362–363 wealth/resources
poverty 398–399 gene flow 66–67 and life span 539
Turkana project 587 genetic 48, 51, 272, 329–331 and menopause 539
Tuskegee Syphilis Study 145 within groups 270 weaning 381–382, 432, 542–543;
twin studies 60, 552 insulin/energy sequestration 134 see also breast feeding,
twinning, parental investment 535 intraspecific, leptin structure/ child care
two compartment model of body function 135 websites
composition 117 leptin structure/function 135 ethics 150, 151, 153
typhoid fever 469 longevity/senescence 545 genetics 72
typology see race/typology male quality/marriage market IMGT/HLA Database 229
447–448; malaria 474
UK (United Kingdom) 33–36, 95 male reproductive endocrinology 134 National Center for Biotechnology
ulcerative colitis 495 mate choice 299–301, 301–302 Information 214
ulcers, gastric/duodenal 228, 503, 512 Mendelian genetics 50 pollution 567, 568
ulna styloid measurements 107, 109 mutation 8, 65–66 weighing scales 99
ultimate determinants of disease 502 origin of 3 weight; see also body mass index,
ultraviolet radiation (UVR) 192, 195, ovarian function 329–331 obesity
197–198, 199–202; see also skin phenotypic 4 normal, and hypertension 497
coloration within populations 3–4 measurement 99
umbilicus measurements 109 and sexual reproduction 317 Weiner, Joseph S. 34–35, 37
UNESCO (United Nations, succeptibility to pollution 575 Weismann, F. L. A. 528
Educational, Scientific and testosterone levels in males Wenner-Gren Foundation for
Cultural Organization) 38 363–364 Anthropological Research
unimodel mismatch distributions 247 thyroid hormones 135 36, 38
United Kingdom 33–36, 95 vasopressin 279, 281–282, 282–283 Westermarck effect 312
United States 33–36, 95 neuroendocrinology of affection 411 Western lifestyles 493, 581
units of measurement, pair bonds 413 hormone level norms 331–332;
anthropometry 93 parental care 411–412, 412–413 see also discordance hypothesis,
urbanization 559, 586; see also cultural VE (pulmonary ventilation) 172, 181 metabolic syndrome, thrifty
transitions, pollution vegan diets 401 genotypes
urine, hormone form/function/ vegetarian diets 401 Western Profile index 592
assessment 128 ventilatory control, altidudinal wet nursing 449
US (United States) 33–36, 95 adaptation 180–181 whales, longevity/senescence
usufruct 444 vertex of skull measurements 107, 109 536, 538
Index 627
whole body potassium counting 116, World War II 33 Yanomami peoples 145, 146, 224,
117, 118 Wright, Sewall 71 497, 536
WHR (waist-to-hip ratio) 328–329 writing 558 Yearbook of Physical Anthropology 34
Wilson, E. O. 529 yusho disease 570
women see females X chromosome 252–253, 280
work capacity see physical activity Xavante peoples 224 Zaire 326
work efficiency (WE) 177 Zetia 505
World Ethnographic Sample 390 Y chromosome 247–248, 248, zinc deficiency, and infection 398
World Health Organization 146, 252–253, 280 Zocor 505
161, 164 Y chromosome Adam 248 zoonotic infections, definition 468

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HUMAN EVOLUTIONARY BIOLOGY

Wide-ranging and inclusive, this text provides an invaluable review of an expansive

Michael P. Muehlenbein is an assistant professor of anthropology at Indiana

Cambridge University Press

# Cambridge University Press 2010

This publication is in copyright. Subject to statutory exception

First published 2010

Printed in the United Kingdom at the University Press, Cambridge

Library of Congress Cataloguing in Publication data

ISBN 978-0-521-87948-4 Hardback

Cambridge University Press has no responsibility for the persistence

List of contributors page vii 11 Human Adaptation to High Altitude 170

12 Skin Coloration 192

1 Evolutionary Theory 3 13 Classic Markers of Human Variation 214

2 The Study of Human Adaptation 17 14 DNA Markers of Human Variation 238

4 Genetics in Human Biology 48 16 The Evolution and Endocrinology

6 History, Methods, and General

Part II Phenotypic and Genotypic Variation 155

24 Evolutionary Biology of Hormonal Responses 30 Beyond Feast–Famine: Brain Evolution,

26 Embodied Capital and Extra-somatic Wealth 32 Evolutionary Psychiatry: Mental

33 Industrial Pollutants and

28 Complex Chronic Diseases

Barry Bogin Paul W. Ewald

S. Boyd Eaton James Holland Jones

Guillaume Evanno Laura L. Jones

Hillard S. Kaplan Royal Children’s Hospital

Theory and Methods

“The natural phenomena of the evolutionary history of

INTRODUCTION systems of organs, to entire organisms. For example, the

genetic adaptation. In this context, functional adapta- ACCLIMATIZATION

ACCOMMODATION AND ADAPTATION is an important mechanism that facilitates human

CULTURAL AND TECHNOLOGICAL GENETIC ADAPTATION AND ADAPTABILITY

when it is unique to the individual or population and

INTRODUCTION biology will be traced through the contributions of

was editor in the 1930s. It is probably the case that

the 15th Cold Spring Harbor Symposium on Quantitative

human biology of Tanzanian Hadza hunter-gatherers

AFTER THE MIDDLE OF THE TWENTIETH

After 1950, new directions were taken in climatic morph-

1. Why is “race” an inappropriate concept to apply to

notion of inheritance known as Pangenesis, that

thus does not contribute to genetic variation nearly as

However, if dominant they will appear more often in

Enhancer sequences Promoter Poly-A addition site

5′ Cap Leader Trailer Poly-A tail

understanding of molecular genetics. For example, 5′ 3′

DNA and RNA A T

The complex molecule that comprises the genetic G C

MITOSIS Prophase Metaphase Two daughter cells

Centromeres divide and sister

4.7. Mitosis. From Futuyma (1998), p. 32.

Mechanisms of transcription frame is specified by an initiation codon (AUG). The

Several chapters in this volume deal with phenotypic

TABLE 4.2. Hypothetical frequencies for applying

forms, positive assortative mating (or homogamy), MICROEVOLUTIONARY PROCESSES

Time + Variation + Natural Selection → Evolutionary adaptation

Modern Synthetic Theory:

Time + Variation + Population + Selection → Evolution

(includes (includes (leads to (as genetic

Measure n MeanSD n MeanSD n MeanSD