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Mitochondrial inheritance: Diverse patterns and mechanisms with an

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 PROOF COVER SHEET
Journal acronym: TMYC
Author(s): Amanda J. Wilson and Jianping Xu
Article title: Mitochondrial inheritance: diverse patterns and mechanisms with an emphasis on fungi
Article no: 684361
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 Mycology
Vol. 00, No. 00, Xxxx 2012, 1–9

Mitochondrial inheritance: diverse patterns and mechanisms with an emphasis on fungi

Amanda J. Wilson and Jianping Xu*
Department of Biology, McMaster University, 1280 Main Street W., Hamilton, Ontario, L8S 4K1 Canada
(Received 29 December 2011; final version received 19 March 2012)

5 In eukaryotic cells, mitochondria play essential roles by generating the universal energy currency, adenosine triphosphate
(ATP), through oxidative phosphorylation to support cellular activities. Similar to chloroplasts in plants and algae, but unlike
other intracellular organelles, mitochondria contain their own genetic materials. The mitochondrial genes and genomes
are inherited differently and independently from that of nuclear genes and genomes. While uniparental (and maternal)
mitochondrial inheritance is the dominant pattern, there is a surprisingly large diversity of other inheritance modes, especially
10 in fungi. Closely related species, or even different strains of the same species, can have different mitochondrial inheritance
patterns in the fungal world. In this review, we describe the diversity of mitochondrial DNA inheritance patterns with an
emphasis on fungi. Whenever possible, the mitochondrial inheritance patterns observed in fungi are compared with those
in other eukaryotes to draw general conclusions about the mechanisms of mitochondrial inheritance in eukaryotes. The
inheritance patterns derived from both laboratory crosses and natural populations are reviewed. In addition, we discuss the
15 potential roles of hybridization on mitochondrial inheritance.
Keywords: uniparental inheritance; biparental inheritance; heteroplasmy; mtDNA leakage; mtDNA recombination

Introduction Uniparental mitochondrial inheritance: the dominant

The mitochondrion (singular, plural mitochondria) is a pattern in eukaryotes including fungi
key organelle in eukaryotic cells. It generates the univer- One very prevalent pattern of mitochondrial inheritance is
20 sal energy currency, adenosine triphosphate (ATP), from uniparental, which indicates that, in a given cross, virtually
organic compounds through oxidative phosphorylation. all the mtDNA in almost all of the progeny comes entirely 45
Different from the majority of organelles in eukaryotic from only one of the two parents. This pattern is seen nearly
cells, mitochondria (along with chloroplasts in plants and ubiquitously across the animal kingdom and in many plants
algae) contain their own genetic material, which is inher- as well as protozoa and fungi (Birky 1995, 2001; Xu 2005).
25 ited independently of the nuclear genome. Unlike that While uniparental mtDNA inheritance is often used to infer
of the nuclear genes and genomes, the inheritance of those whose progeny inherit mtDNA exclusively from one 50
mitochondrial genes and genomes does not follow the parent, it also includes cases where the progeny inherit
typical Mendelian principles of segregation and inde- mtDNA mostly from one parent with a small proportion
pendent assortment. Indeed, many mitochondrial inheri- (that we call mtDNA leakage) from the other parent. In the
30 tance patterns have been observed, especially in fungi. animal kingdom, uniparental mitochondrial inheritance is
Closely related species, or even different strains of the typically exclusively from the maternal parent, but leakage 55
same species, can have different mitochondrial inheri- has been observed in hybrid crosses between closely related
tance patterns. In this review, we describe the diver- species, which will be discussed in a later section. Since
sity of mitochondrial DNA (mtDNA) inheritance patterns, uniparental mitochondrial inheritance is so widespread,
35 along with the (potential) mechanism(s) for such patterns. biologists have sought to determine what mechanisms (at
As shown below, among the different groups of eukaryotes, the molecular, genetic, cellular, developmental, and evolu- 60
fungi seem to contain the most diverse mtDNA inheritance tionary levels) are responsible for the phenomenon. There
patterns and may represent the best models from which to are many stages at which control mechanisms can be in
understand the mechanisms and evolution of mitochondrial place to ensure that only one parent’s mitochondria is
40 inheritance in general. inherited in the offspring. We separate these mechanisms

*Corresponding author. Email: jpxu@mcmaster.ca

ISSN 2150-1203 print/ISSN 2150-1211 online

© 2012 Mycological Society of China
http://dx.doi.org/10.1080/21501203.2012.684361
http://www.tandfonline.com
 2 A.J. Wilson and J. Xu

65 into three distinct categories and present them below. These fertilization have been hypothesized as the determinants for
categories include mechanisms that operate during the paternal mitochondrial inheritance.
production of gametes, during fertilization or fusion of While the above pre-zygotic mechanisms can help 120
gametes, and after the zygotes are formed. explain the absence of mitochondria in the progeny from
one parent in sexual crosses in plants and animals, they
cannot explain uniparental mitochondrial inheritance in
Mechanisms during gametogenesis single-celled eukaryotes such as the fungi Cryptococcus
70 In sexual crosses in plants and animals, events before neoformans, Ustilago maydis or the alga Chlamydomonas 125
fertilization can dictate the mitochondrial inheritance pat- reinhardtii. In these organisms, there is no or little dif-
tern. The main event before fertilization that can cause ferentiation in size or morphology between gametes from
the uniparental inheritance pattern is the exclusion of different parents. In addition, during the formation of sex-
mitochondria from the gametes in one of the sexes, cre- ual offspring, the isogamous cells often fuse to form a
75 ating gametes that have no possibility of contributing larger zygote, leaving no sperm tail or the cytoplasm from 130
mitochondrial to the progeny. The earliest example of this one parent behind. As a result, to account for uniparental
mechanism was noted by Moses (1961) in the red crayfish mtDNA inheritance in these isogamous species, other pro-
Procambarus clarkii. He showed that there was no mito- cesses must be involved during or after the fusion of the
chondrion in the gametes of male crayfish at the final stages gametes. In the following two sections, we describe the
80 of spermatogenesis. Specifically, microscopic observations diversity of fertilization and post-fertilization mechanisms 135
showed that during those stages, the mitochondria were that contribute to uniparental mtDNA inheritance.
segregated into peripheral cells that were not to become
sperm. This observation was completely unexpected as it
had been assumed that sperm required energy and, there- Fertilization mechanisms
85 fore, mitochondria to find and fertilize eggs. In this species, During fertilization in plants and animals, several mecha-
however, the sperm lack flagella and are kept in a cav- nisms have been found to contribute to uniparental inher-
ity in the female after copulation in which they fertilize itance of mitochondria. In some species, the paternal 140
eggs as they pass through the cavity. This lack of energy mitochondria are lost before the sperm enters into or fuses
requirement to move and find eggs and further the lack with the egg. In others, the paternal cytoplasm is excluded
90 of flagella on the sperm could have contributed to the from the egg upon fertilization.
evolution of mitochondrial exclusion in the sperm of this In the tunicate Ascidia nigra, the mature sperm only
species. Similar to that in crayfish, some members of the contains one mitochondrion, which disappeared just before 145
plant Orchidaceae family (i.e. orchids) have also exhibited the sperm enters the perivitelline space and fertilizes the
a lack of mitochondria in the generative cell (progenitor egg (Ursprung and Schabtach 1965). This observation
95 cell of the haploid pollen grain) as shown by transmission was made in a microscopic study of the fertilization pro-
electron microscopy (Yu and Russell 1992). The exclusion cess that showed the paternal parent did not contribute
of mitochondria in orchid pollen was likely mediated by mitochondrion to the offspring in A. nigra. 150
actin, a component of the cytoskeleton, along with several Another mechanism in which the paternal
biochemical gradients (reviewed in Mogensen 1996). mitochondria are excluded is that the sperm cytoplasm
100 For the majority of plants and animals, the dominant remains outside of the egg upon fertilization. Enucleated
mechanism for uniparental mitochondrial inheritance is cytoplasmic bodies, slightly smaller than sperm cells, have
also related to gametogenesis, during the production of been observed outside of recently fertilized embryos in 155
anisogamous gametes. In these organisms, sperm are typ- cotton (Jensen and Fisher 1967) and these were confirmed
ically small and contain relatively few mitochondria in to be of sperm origin. These same types of cytoplasmic
105 their cytoplasm. In contrast, eggs are large and contain bodies have also been reported in plants such as Populus
many mitochondria. As a result, there would be signif- deltoids (Russell et al. 1990) and tobacco (Huang et al.
icantly biased contributions of mitochondria and cyto- 1993). 160
plasm between the two parental gametes during mating, Although these processes can help explain the mech-
in favour of those from the maternal parent (Birky 1995, anisms by which uniparental mitochondrial inheritance
110 2001; Reboud and Zeyl, 1994; Xu 2005). Unlike those in occurs, much remains unknown about the genetic con-
animals and the angiosperms, the sperm in certain gym- trols of these processes. One reason for the lack of
nosperms such as Biota orientalis (Chinese cedar) are understanding of the genetic determinants for uniparental 165
large and contain similar numbers of mitochondria to that mitochondrial inheritance is because these processes have
in eggs of other species (Chesnoy 1977). Interestingly, only been characterized by microscopic and cytological
115 mitochondria are inherited paternally in these gym- investigations of the mating process between significantly
nosperms. In these organisms, the size and compositional differentiated gametes. These processes also cannot explain
differences along with steps that occur during and after what happens in organisms where sexual progeny is 170
 Mycology 3

generated by the fusion of cells. Similarly, they cannot In the second type of post-fertilization mechanism,
explain uniparental mitochondrial inheritance in species there is selective degradation of mitochondria from one 225
that contain many plastids and/or mitochondria upon fertil- parent. Two selective degradation pathways have been
ization but do not actively exclude cytoplasm or organelles proposed and each has received some experimental sup-
175 from either parent during fertilization. port. The first of these two pathways involves targeted
ubiquitination of the sperm mitochondria, followed by
degradation by the lysosome. Ubiquitination of sperm 230
Post-fertilization mechanisms mitochondria has been observed in mammals such as
If the above-described pre- and during- fertilization mech- bovine, rhesus monkey, mice and humans (Sutovsky et al.
anisms were not involved in uniparental mitochondrial 1999, 2000), but not in other eukaryotes. These researchers
inheritance, mitochondria of both parents would be present showed, by immuno-fluorescence microscopy, that when
180 in the zygote or the embryo after fertilization. To ensure bull mitochondria entered the cow’s eggs, ubiquitin 235
uniparental mitochondrial inheritance in these organisms, was added to the membrane of sperm mitochondria.
post-fertilization mechanisms must be operating. Two Later, when the fertilized egg underwent pre-implantation
types of such mechanisms have been identified. These (4–8 cell stage), the fluorescently dyed sperm mitochondria
mechanisms are described below. disappeared. The authors initially suggested that this was
185 In the first, mitochondria from one parent are due to proteosome-mediated proteolysis. However, none of 240
sequestered away from the portion of the egg that the 17 proteosome-specific antibodies that they used could
eventually develops into the progeny, thus resulting in detect proteosomes in association with the ubiquitinated
the inheritance of mitochondria from the other par- sperm mitochondria (Sutovsky et al. 1999). Later, fur-
ent. Organelle sequestration has been found primarily ther examinations of the destruction of ubiquitinated
190 in plants. For example, Owens and Morris (1991) per- mitochondria were observed through the application of 245
formed a cytological study on Douglas fir, Pseudotsuga a lysomotropic agent (which inhibits the normal func-
menziesii of the Pinaceae family, to examine the mech- tion of maternal lysosomes). The agent was applied to
anisms behind the pattern of mitochondrial inheritance fertilized eggs with tagged lysosomes and observed by
in this group of plants. Unlike some gymnosperms men- electron microscopy. The authors demonstrated that the
195 tioned above, progeny from crosses in this plant family sperm mitochondria were degraded by lysosomes, not by 250
inherit mitochondria from the female parent. Owens and proteosomes, since the lysomotropic agent inhibited the
Morris (1991) showed that at the time of fertilization, removal of sperm mitochondria (Sutovsky et al. 2000).
sperm cells have many mitochondria, as do egg cells. The second degradation mechanism involves methy-
Furthermore, during fertilization, all of the cytoplasm from lation of organelle DNA from one parent that provides
200 the sperm enters the egg. Shortly after gamete fusion, protection from degradations, while the unmethylated 255
the female mitochondria form a dense mass around the and unprotected organelle DNA is degraded. This selec-
egg nucleus as the nucleus moves to one end of the cell. tive methylation and degradation mechanism has been
As the sperm nucleus moves towards the egg nucleus to reported as a component of organelle discrimination in
fuse, the male mitochondria trail behind the male nucleus. algae (Nishiyama et al. 2002, 2004). Although this exam-
205 When the male and female nuclei fuse, the fused nucleus ple is not on mitochondria but on chloroplasts, it is still 260
is surrounded only by female mitochondria. While this an excellent demonstration of a potential mechanism to
mechanism has been described, the underlying genetic mediate uniparental organelle inheritance and its principles
determinant(s) and molecular mechanism remain incom- may be applicable to uniparental mitochondrial inheritance.
pletely understood. In addition, there is also a possibility The first evidence for protective methylation of organelles
210 for leakage in this system and other mechanism(s) are was shown in the green alga Chlamydomonas reinhardtii. 265
likely needed to ensure uniparental mitochondrial inheri- In this species, the two mating types are mt+ and mt-,
tance. Furthermore, cytological evidence for a variant of with mt+ being the parent that transmits chloroplasts to
this process has been shown in Biota orientalis where sexual offspring. During sexual matings, two gametes of
mitochondria are paternally inherited (Chesnoy 1977). opposite mating types fuse, with each parent contributing
215 In this species, there is no mass of female mitochondria similar amounts of organelles to the zygote, but almost 270
around the nucleus after fertilization. Instead, the male all progeny will have only the mt+ chloroplasts. It has
cytoplasm (containing many mitochondria) remains tightly been shown by Nishiyama et al. (2002) that mt+ chloro-
associated with the sperm nucleus which migrates towards plast DNA (cpDNA) is far more methylated than those
the egg nucleus at one end of the zygote. Upon fusion of mt- cells. A methyltransferase, DMT1, was detected to
220 of the nuclei, the egg mitochondria migrate away from target chloroplasts and was expressed at a much higher 275
the fused nucleus and begin to be degraded while the level during gametogenesis of the mt+ cells than that of
sperm mitochondria remain closely associated with the the mt- cells. Additionally, when this methyltranferase was
nucleus. overexpressed in mt- cells, cpDNA from the mt- cells was
 4 A.J. Wilson and J. Xu

transmitted to the next generation. The authors suggested (Yan et al. 2004, 2007a,b), suggesting that other targeted
280 that this methylation protected the mt+ cpDNA from selection/degradation mechanisms must exist to maintain 335
degradation by nucleases after the fusion of the gametes. uniparental mitochondrial inheritance in this organism.
Later, Nishiyama et al. (2004) determined that this pro- These studies also identified that two specific genes,
tective methylation was only partially responsible for sxi1alpha and sxi2a, found in the mating type locus of the
uniparental cpDNA inheritance. They showed that pater- MATα and MATa strains, respectively, interact to control
285 nal and biparental cpDNA inheritance was increased by mitochondrial inheritance. Deletion of either or both 340
∼20% between matings of transgenic mt- Chlamydomonas genes resulted in biparental mitochondrial inheritance,
(with mt+ DMT1) and wild type mt+ when compared to with plenty of evidence for mtDNA recombination in the
wild-type matings. progeny (Yan et al. 2004, 2007a). The importance of these
In the corn smut fungal pathogen Ustilago maydis, two genes to interact with each other and control mtDNA
290 mitochondria are generally inherited uniparentally, from inheritance was further supported by the biparental 345
the a2 strains. By using various knockouts of genes present mtDNA inheritance seen in same-sex mating between
only at the a2 mating type locus, lga2 and rga2, Fedler strains of the MATα mating type (Yan et al. 2007a).
et al. (2009) showed that when the Lga2 protein was not Interestingly, environmental and other genetic factors have
present in the a2 strain, mitochondria were inherited from also been found to impact mitochondrial inheritance in C.
295 both parents, along with the generation of recombinant neoformans. Specifically, UV irradiation and temperature 350
mtDNA molecules. In contrast, if the Rga2 protein was were found to significantly impact mitochondrial inheri-
not present in the a2 strain, mitochondria were inherited tance pattern. At high temperatures and with significant
from the a1 strain. Furthermore, if the rga2 gene was UV exposure, biparental mitochondrial inheritance and
transformed into the a1 strain, mitochondria were trans- mtDNA recombination were found in the progeny (Yan
300 mitted from both parents. These results suggested that et al. 2007b). Furthermore, mating between haploid and 355
the Rga2 protein protected the mitochondria from degra- non-haploid strains showed a different mtDNA inheritance
dation by the Lga2 protein in a2 strains of U. maydis. pattern than the typical haploid×haploid mating, with
However, the authors did not provide an explanation for significant mtDNA contributions from the MATα parent
why mitochondria were inherited from the a1 parent when (Skosireva et al. 2010). These observations suggest the
305 the rga2 gene was not present in the a2 strains. This mech- potential adaptive significance of the different modes of 360
anism may be similar to that of protective methylation as mitochondrial inheritance in C. neoformans. Whether or
the Rga2 protein may directly or indirectly methylate a2 not these factors impact mitochondrial inheritance patterns
mtDNA, while the Lga2 protein interferes with mtDNA sta- in other organisms remains to be examined.
bility, either directly or indirectly, including controlling the
310 expression of a mitochondrial nuclease that degrades any
unprotected mitochondrial DNA (Mahlert et al. 2009). Other modes of mitochondrial inheritance in fungi
In the human pathogenic basidiomycete yeast While uniparental mitochondrial inheritance is the dom- 365
Cryptococcus neoformans, mitochondrial inheritance is inant mode of mitochondrial inheritance in eukaryotes,
uniparental, from the MATa parent regardless of other other patterns of inheritance have also been observed, pre-
315 characteristics exhibited by the progeny itself (Xu et al. dominantly in fungi but also in other eukaryotes. The
2000; Yan and Xu 2003). It was originally hypothesized alternate patterns have been collectively called “biparental
that two cells of opposite mating types in C. neoformans mitochondrial inheritance”, because the progeny inherit 370
would fuse together at the onset of mating and some mitochondria from both mating contributors, creating
mechanism afterwards would selectively degrade the offspring with either or both parental mitochondrial
320 MATα mitochondria. Later cytological observations DNA sequences. However, when discussing biparental
showed that unidirectional migration of nuclei could play mitochondrial inheritance, it is important to note the
a role in the inheritance of mitochondria of C. neoformans. specifics of the progeny cells that were analysed. As shown 375
McClelland et al. (2004) stained two different parental below, this is especially the case in fungi where sam-
strains and observed the MATα nucleus migrate into the ple location of the progeny can play a significant role in
325 MATa parent via a conjugation tube. After migration of the determining the mitochondria that they can inherit.
MATα nucleus into the MATa cell, the signature mating In filamentous Basidiomycete fungi, mating occurs by
products, hyphae, were seen growing only from the MATa the fusion of two haploid homokaryons (i.e. hyphae with 380
side of the pair. As a result, progeny developed from these one or more nuclei of the same genetic makeup in each
hyphae would contain mtDNA from only the MATa parent. cell), creating a heterokaryon (i.e. hyphae with at least
330 However, in later studies, where hyphal growth was elimi- two haploid nuclei of different genotypes in each cell)
nated from crosses (by limiting mating to only a short time (Figure 1). In some rare instances, a diploid monokaryon
before hyphae had the opportunity to develop), uniparental may be generated instead of a heterokaryon. At the ter- 385
mitochondrial inheritance was still the dominant pattern mini of dikaryotic hyphae, the haploid nuclei fuse and
 Mycology 5

Homokaryon 1 Homokaryon 2
population while the donor homokaryon maintains its own
nuclear and mitochondrial genomes. In addition, May and
Taylor (1988) showed that dikaryotic cells at the junc-
tion where mating partners meet contained mtDNA from 420
Mycelial fusion both mating partners, creating heteroplasmic cells. These
results showed that, within a mated hyphal super-colony,
the individual mtDNA types of the mating partners, a mix-
ture of the two and recombinant(s) of the two parental
types all were observed in individual cells depending 425
Nuclear division and migration upon where progeny samples were taken for analyses.
This sample location-dependant mitochondrial inheritance
(Yan and Xu 2005) was also found in several other basid-
iomycetes including Pleurotus ostreatus (Matsumoto and
Fukumasa-Nakai 1996), Agrocybe aegerita (Barroso et al. 430
1997), Agaricus bisporus (Jin and Horgen 1994) and
Figure 1. Simplified schematic representation of mating Agaricus bitorquis (Hintz et al. 1988). Furthermore, a sim-
and sample location-dependent mechanism of uniparental ilar phenomenon has also been observed in fliamentous
mitochondrial inheritance in filamentous fungi. Open and filled ascomycetes Aspergillus nidulans (Coenen et al. 1996),
small circles represent different mitochondria from the two par-
ents. Open and filled irregularly shaped stars represent the nucleus
Neurospora crassa (Mitchell and Mitchell 1952) and 435
of the two parents. After hyphal fusion, the nuclei in the apical Podospora anserina (Belcour and Begel 1977). The sample
cells of the parents divide and migrate (horizontal arrow) to the location-dependent pattern of mitochondrial inheritance is
cells of the mating partner while mitochondria do not migrate. the most commonly reported so far among filamentous
The heterokaryotic hyphae at the two ends of this mating event fungi and is functionally analogous to the sequestration-
(vertical upright arrow) would contain the same nuclear genomes
from both parents but different mitochondrial genomes.
based fertilization mechanism discussed earlier in this 440
review.
form a diploid nucleus, which is then followed by meiosis The sample location-dependant mitochondrial inher-
and the production of basidiospores. In the inkcap mush- itance pattern is found not only in filamentous fungi
room Coprinopsis cinerea ( syn. Coprinus cinereus), the described above, but also in ascomycete yeasts such as
390 mitochondrial inheritance at an individual progeny cell Saccharomyces cerevisiae (Thomas and Wilkie 1968), 445
level is uniparental as each cell typically inherits mtDNA Saccharomyces castellii (Peterson et al. 2002), and
from only a single parent (Baptista-Ferreira et al. 1983). Schizosaccharomyces pombe (Thraikill and Birky 1980).
However, when considering the whole mating colony as an However, there are some differences between filamentous
individual, the mitochondrial inheritance would be consid- fungi and yeasts. For example, in the yeasts exhibiting
395 ered biparental as different cells in the dikaryotic colony sample location-dependant mitochondrial inheritance, mat- 450
contain different mtDNA types but with the same nuclear ing begins with the fusion of two compatible cells and
genotype (Yan and Xu 2005). This pattern occurs because ends with a much larger zygote cell. As a result, the
of the reciprocal migration of haploid nuclei during mat- zygotes are naturally heteroplasmic and recombination
ing, unaccompanied by mitochondria, into the recipient can occur between the parental mitochondrial genomes
400 homokaryon (Figure 1). Since the mitochondria are not (Figure 2). However, the mitochondrial genotype of the 455
migrating, only the resident mitochondria in the individual budding progeny zygotes depends on the proximity of
dikaryotic cells will be inherited, causing uniparental inher- the budding site relative to the junction zone where the
itance to be observed in most cells, especially for those two parental cells fuse. Specifically, when the budding
located at a distance from the mating junction (Figure 1; progeny of zygotes are taken from either pole of the newly
405 Yan and Xu 2005). However, within the whole colony of formed zygote, they exhibit uniparental inheritance of 460
mated dikaryotic cells, both parental mitochondrial types mitochondria from the parent of that end (Figure 2). In con-
can be observed (Baptista-Ferreira et al. 1983). trast, if sampling is done near the junction of the mated
While mosaic mitochondrial genotypes in a uniform zygote, those zygote buds often contain mitochondria
nuclear genotype background is the dominant pattern in from both parents and show heteroplasmic inheritance of
410 mating colonies in C. cinerea and other filamentous basid- mitochondria or have recombinant mitochondrial geno- 465
iomycetes (Yan and Xu 2005), significant variations have types (Figure 2; Strausberg and Pelman 1978; Zinn et al.
been reported among strains and strain pairs. For example, 1987).
May and Taylor (1988) showed that in some compatible The final type of non-uniparental mitochondrial inher-
crosses in C. cinerea only one mating partner’s nucleus itance in fungi is called doubly uniparental or progeny
415 migrated into the other monokaryon, creating a dikaryon sex-dependent mitochondrial inheritance. This was first 470
with only one mtDNA genotype in the dikaryotic hyphal observed in the basidiomycete Microbotryum violaceum
 6 A.J. Wilson and J. Xu

observed in a diverse group of organisms such as the fruit

MATa MATα flies (Kondo et al. 1990), pine trees (Wagner et al. 1991), 500
mice (Gyllensten et al. 1991; Shitara et al. 1998), mussels
(Zouros et al. 1994; Rawson et al. 2006), and periodical
cicadas (Fontaine et al. 2007). Furthermore, leakage has
Mating been inferred from the discovery of recombinant mtDNA
genotypes in surveys of hybrid zones in the great tit (Kvist 505
et al. 2003), spruce trees (Jaramillo-Correa and Bousquet
2005), silk moths (Arunkumar et al. 2006), and the human
fungal pathogen Cryptococcus gattii (Xu et al. 2009).
Below, we briefly describe evidence of mtDNA leakage
MATa MATα and recombination in natural hybrids of the human fungal 510
mtDNA mtDNA pathogen Cryptococcus gattii.
type type
C. gattii is a close relative of C. neoformans. In C.
neoformans, there are two main lineages C. neoformans
Mixture of MATa and var. neoformans (serotype D) and C. neoformans var. gru-
MATα mtDNA type
bii (serotype A). Laboratory crosses involving strains of 515
Figure 2. Simplified schematic representation of mating and MATa and MATα from within serotype D of C. neofor-
sample location-dependent mechanism of mitochondrial inheri- mans have shown uniparental mtDNA inheritance, from the
tance in the model yeast Saccharomyces cerevisiae. Open and MATa parent (Yan and Xu 2003). Furthermore, no leak-
filled small circles represent different mitochondria from the two age of the MATα mtDNA was found in 570 progeny of six
parents. Open and filled irregularly shaped stars represent the hybrid crosses between strains of serotype A and serotype 520
nucleus of the two parents. After cell fusion, the nuclei from the
two parental cells fuse while mitochondrial remain relatively sta- D (Xu et al. 2000) in C. neoformans. Similar to C. neofor-
ble in their positions. Depending on the budding position of the mans, there are two mating types in C. gattii, also called
progeny, their mitochondrial genotypes could differ. MATa and MATα. Four divergent lineages have been dis-
tinguished within C. gattii and these are called VGI, VGII,
( syn. Ustilago violacea) where progeny with the a1 mat- VGIII, and VGIV (Bovers et al. 2008). 525
ing type inherit mitochondria from either parent equally At present, the mtDNA inheritance patterns in both
while progeny of the a2 mating type predominantly intra- and inter- lineage laboratory crosses in C. gattii
475 inherit mitochondria from the a2 parent (Wilch et al. have not been described. However, unambiguous evidence
1992). A similar pattern of inheritance has also been for recombination and hybridization was identified in the
observed in blue mussels and is unique in that the female mitochondrial genomes in natural populations of C. gattii 530
progeny inherit only female parental mitochondria, but (Xu et al. 2009). In this study, sequences of five mtDNA
the male progeny inherit both male and female parental gene fragments were obtained from 50 isolates belonging
480 mitochondria (Zouros et al. 1994). to two of the four lineages in C. gattii, VGI (22 strains) and
VGII (28 strains). While mostly consistent, the five individ-
ual gene genealogies showed slight but significantly differ- 535
Hybridization and mitochondrial inheritance ent relationships among the isolates, indicating evidence
As discussed above, many species, especially those in the for recent hybridization and mitochondrial gene transfer
animal kingdom, have shown uniparental mitochondrial between the two lineages. In addition, the data provided
inheritance in sexual crosses. These results have been clear signatures of recombination among mitochondrial
485 obtained from mating between individuals of the same genes within the VGII lineage (Xu et al. 2009). 540
species. In crosses between individuals from different Several hypotheses were proposed to explain the
species or between divergent populations of the same observed hybridization and recombination in the
species, mitochondrial inheritance patterns could change mitochondrial genomes of these two lineages. These
and be different from the typical uniparental inheritance include the lack of stringent control of uniparental mtDNA
490 pattern (Gyllensten et al. 1985, 1991; Zouros et al. 1994). inheritance in C. gattii as was found in C. neoformans, 545
In cases of hybridization between species or subspecies, the the product of same-sex mating in nature between strains
intraspecific uniparental mitochondrial inheritance pattern of the MATα mating type, and/or the exposure of strains
could be altered due to the breakdown of mechanisms gov- to stresses such as high temperature and UV irradiation
erning uniparental inheritance and result in the presence during mating (Xu et al. 2009). Same-sex mating and
495 of organelle DNA from the parent that usually does not exposure to high temperature and UV irradiation during 550
contribute. The leakage could result in recombination of mating have been shown to promote biparental mtDNA
mitochondrial genomes. Indeed, direct evidence for leak- inheritance and mtDNA recombination in C. neoformans
age of mitochondrial DNA after hybridization has been (Yan et al. 2007a,b). The observed hybridization and
 Mycology 7

recombination in the mitochondrial genomes of natural Conclusions and perspectives

555 populations of C. gattii may represent an adaptive response In this review, we have shown a diversity of mitochondrial
for this organism to adverse environmental conditions. inheritance patterns across the eukaryotic domain but with 610
For example, generating diverse mitochondrial genotypes a special focus on fungi. The comparison between fungi
could help counter-balance environmental fluctuations and other eukaryotes was necessary to gain a more com-
and avoid mutational meltdown of the mitochondrial plete understanding of the underlying mechanisms of the
560 genome due to increased mutations (Xu 2005). Whether diverse patterns. As shown above, a large number of pro-
similar phenomena happen in other fungi remain to be cesses can influence mitochondrial inheritance. For exam- 615
explored. ple, the dominant mitochondrial inheritance pattern in
eukaryotes is uniparental, and mostly from the maternal
Evolutionary mechanisms and implications parent. This seemingly simple mitochondrial inheritance
While uniparental mitochondrial inheritance is the domi- pattern could be controlled by many different mechanisms
565 nant pattern, other patterns have also been observed, espe- and at different developmental stages, from pre-zygotic to 620
cially in fungi. In addition, an increasing number of studies post-zygotic. Our review also showed that the group of
indicated that environmental and biological factors could eukaryotic organisms with the most diverse patterns of
also impact mitochondrial inheritance patterns. Together, mitochondrial inheritance is fungi. Indeed, though still at
these studies are consistent with the adaptive significance its infancy, our understanding of the molecular genetic con-
570 of mitochondrial inheritance patterns. Below, we briefly trols of mitochondrial inheritance is probably best under- 625
discuss evolutionary and adaptive significance of various stood in this group of organisms. The diversity of patterns
mitochondrial inheritance patterns. will allow experiments to be designed to address the fun-
Several hypotheses have been proposed to explain damental genetic mechanisms controlling mitochondrial
mitochondrial inheritance and all have focused on explain- inheritance and identify the adaptive significance of these
575 ing the widespread uniparental inheritance pattern across patterns. Thus, it is highly likely that fungi will play very 630
the eukaryotic domain. One hypothesis suggested that the important roles as models from which to understand the
mixing of cytoplasms and mitochondria from two differ- molecular, cellular, developmental, ecological and evolu-
ent parental cell types would create conflicts and result in a tionary mechanisms which underlie the diverse modes of
low fitness for the progeny zygote (Hurst, 1990; Hurst and mitochondrial inheritance.
580 Hamilton, 1992). As a result, the emergence of a suppres-
sor gene that prevented its own mitochondria from being
transmitted would be advantageous in mating and produc- Acknowledgements 635
ing fitter offspring. The authors further suggested that the Our research on fungal mitochondrial inheritance and evolu-
origin and evolution of uniparental mitochondrial inheri- tion has been supported by the Natural Science and Engineering
585 tance might have played a key role in the evolution of sex Research Council of Canada.
(Hurst and Hamilton 1992; Billiard et al. 2011). However,
there is currently no experimental evidence for cytoplas-
mic conflict. Recent data showed that progeny zygotes with References
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