Unit-IV

Mutations
 Introduction
• A heritable change in the sequence of nucleotide of DNA brings sudden
change in morphological characteristics of an organism is called Mutation.
• Organism with mutation is called mutant while the organism without
mutation is wild type.
• The majority of mutations are harmful because they alter some aspect of
cellular activity in a negative way.
• For example, perhaps a mutation causes an enzyme to fold incorrectly,
shutting down an important metabolic pathway in a cell.
• However, as points out, on rare occasions, a mutation can be beneficial and
give the organism a novel property, such as an increased potential of causing
disease.
 Types of Mutations
1) Spontaneous mutations
2) Induced mutations- mutagens-Physical and Chemical
Based on change in genotype and phenotype
3) Point mutations- Transition, Transversion
Based on Transcriptional property
Silence
Mis-sense
Non-sense
4) Frame shift mutations
5) Chromosomal abberations- deletions, inversions, tandem duplications,
insertions
 Mutations can be Spontaneous and Induced
• Spontaneous mutations are heritable, random changes to the base
sequence in the DNA that result from natural phenomena.

• These changes could result from errors made and not corrected by DNA
polymerase during replication or from physical or chemical agents in the
environment.

• It has been estimated that one such mutation can occur for every 106 to
1010 divisions in a bacterial population.

• A mutant cell arising from a spontaneous mutation usually is masked by the

much larger population of normal cells.

• However, should the environment favor the mutant, it will multiply and
emerge as the predominant form.
• For example, for many decades doctors used penicillin to treat gonorrhea,
which is caused by Neisseria gonorrhoeae.

• Then, in 1976, a penicillin-resistant strain of N. gonorrhoeae emerged.

• Many investigators suggested that the penicillin-resistant strain had

existed in the N. gonorrhoeae population for centuries, but only with
heavy penicillin use in the 1970s could the penicillin-resistant strain arise
and surpass the penicillin susceptible forms.
 Induced mutations

• Induced mutations are developed by external Physical and Chemical

agents called Mutagens.

• Types of Mutagens

• Physical Agents: It includes high energy radiations such as gamma rays, X-

rays and alpha particles and increase in temperature.

• Chemical Agents: They are of various types such as nitrous acid, alkylating
agents, acridines, and base analogues.

• Biological Agents: It includes viruses, bacteria, and transposons.

 Physical mutagens
• Ultraviolet (UV) light is a physical mutagen whose energy causes adjacent
thymine (or cytosine) bases in the DNA to covalently link together forming
dimers.

• If such type of dimers appear in a protein-coding gene, the RNA

polymerase can not place the correct bases (A–A) in mRNA molecules
where the dimers are situated.

• In addition, ionizing radiations, such as gamma rays and X-rays, can cause
physical breaks in the double-strand DNA. Loss of cellular function usually
results.
(A) When cells are irradiated with ultraviolet (UV) light either naturally or through
experiment, the radiations might affect the cell’s DNA. (B) UV light can cause adjacent
thymine molecules to covalently pair (red lines) within the DNA strand to form a
thymine dimer.
 Chemical mutagens
• Many chemicals are mutagenic; that is, they can cause mutations.

• Nitrous acid is an example of a chemical mutagen that converts DNA’s

adenine bases to hypoxanthine bases.

• Adenine generally base pair with thymine, but the existence

of hypoxanthine creates a base pairing with cytosine while replication.

• After, if replication happens from the gene with the cytosine mutation, the
mRNA will have a guanine base insted of an adenine base.
• Mutations also are induced by base analogs, which bear a close chemical
similarity to a normal nucleotide.
• For example, acyclovir is a base analog that can substitute for guanine
during virus replication.
• However, incorporation of acyclovir blocks further viral replication
because the analog lacks the deoxyribose sugar needed for the addition
of the next nucleotide. As a result, new virus particles cannot be
produced.
• Acyclovir, therefore, is an effective treatment to limit infections caused by
the herpes simplex 1 and 2 viruses (cold sores and genital
herpes), varicella-zoster virus (shingles and chickenpox), and Epstein-Barr
virus (mononucleosis).
Based on change in genotype and phenotype,
mutation are of two types

• Point mutations

• Frame shift mutations

 Point mutations
• It occurs as a result of replacement of one nucleotide by other in specific
nucleotide sequence of gene. Point mutation brings little phenotypic
change as compared to frameshift mutation.

Point mutation are two types based on the base pair substitution

• Transition: It is the point mutation occur by substitution of one purine by

another purine or one pyrimidine by another pyrimidine.

• Transversion: It is the point mutation occur by substitution of purine by

pyrimidine and vice versa.
Based on transcriptional property point mutation are of three

types.

i) Silent mutation

ii) Missense mutation

iii) Non-sense mutation

Silent mutations:
It is also known as neutral mutation.
• It is the mutation in which mutated codon codes same amino acids as the
original codon. Since the aminoacid is same as original one, it does not effects
the structure and composition of protein.
• Silent mutation causes phenotype of bacteria remain similar to that of wild
type.
Missense mutation:
• In this mutation mutated codon codes different amino acid (other than
original). Since new aminoacid coded by mutated codon is altered, the protein
formed from it is also altered. Such protein can be less active or completely
inactive.
• If altered aminoacids lie on active site of protein then such protein become
completely non-functional.
• The missense mutation causes phenotypic change in organism.
Non sense mutations:
• Mutation in which altered codon is stop codon or chain
terminating codon, such mutation is called non-sense
mutation.
• Non sense mutation causes incomplete synthesis. Such
incomplete protein is always non-functional.
• Non-sense mutation bring greatest change in phenotype of
an organism.
 Frame shift mutations
• It occurs as a result of addition or deletion of nucleotide in the sequence
of DNA. Addition or deletion of nucleotide causes shift of the reading
frame of mRNA.

• In a mRNA each codon is represented by three bases without punctuation

and insertion or deletion of a nucleotide changes the entire frame. So
frame shift mutation bring greater phenotypic change than point
mutation.

• Insertion or deletion of one or two base pair of nucleotide causes shift in

frame. However, insertion or deletion of three base pair adds or remove
a whole codon, this results in addition of removal of single amino acid
from polypeptide chain.
 Chromosomal aberrations
• Chromosomal abberations or abnormalities are changes to the structure
or number of chromosomes
• They are also called as chromosomal mutations.
• These typically affect more than one gene.
• There are a very common cause of early spontaneous miscarriage.
• These abnormalities in chromosome in number or structure may result in
birth defects, mental retardation and increased risk for infertility
Two types:
• Structural chromosomal aberration
Deletion, Inversion, Insertion, Duplication
• Numerical chromosomal aberration- Polyploidy, Aneuploidy
 Structural chromosomal aberration
• Structural chromosome abnormalities occur when part of a chromosome
is missing, a part of a chromosome is extra, or a part has switched places
with another part leading to too much or too little genetic material.

It may be of following types

• Deletion

• Inversion

• Insertion

• Tandem Duplication
 Structural chromosomal abberations

Deletion:
• It is a loss of a portion of a chromosome.
• It may be caused by heat, radiation, viruses, chemicals, errors in
recombination.
• It is a situation than can be called as partial monosomy (for the portion of
chromosome that is deleted).
• Most segmental deletions are deleterious.
• Large deletions are mostly lethal.
• Smaller deletions may allow survival.
• ─E. coli: deletions of up to 1% have been observed in living cells.
• ─D. melanogaster : deletions of up to 0.1% observed.
Terminal deletion: A single break near the end of a chromosome would be
expected to result in a terminal deficiency

Intercalary deletion: if the deletion occur in between regions of the

chromosome it is a intercalary deletion

Structural chromosomal aberration Deletions in humans

• Cri-du-chat syndrome ─Micro deletion of chromosome 5

• Di-George syndrome ─Micro deletion of chromosome 22

• Schizophrenia & Obsessive Compulsive Disorder ─Micro deletion of

chromosome 22 associated
Inversions

• Inversions originate when parts of chromosome become detached, turn

through 180°, and are reinserted in such a way that the genes are in
reversed order.

• Some inversions presumably result from entanglements of the threads

during the meiotic prophase and from the chromosome breaks that occur
at that time.

• Paracentric inversions are those inversions where inverted segments do

not include centromeres. On the other hand, in a pericentric inversion,
inverted segment includes centromere.
Insertions

• In this type of chromosomal abnormality a portion of a chromosome has

been inserted in an unusual position within the same or another
chromosome. If there is no gain or loss of chromosome material, the
person will be healthy. However, if there is gain or loss of chromosomal
material, the person may have health problems.
Duplications
• In chromosomal duplication, part of the chromosome is duplicated or has
two copies. The result is additional chromosomal material. This extra
chromosomal material can lead to gene malfunctioning, which may cause
learning disabilities, developmental delays and health problems.