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Polyandry and sex-specific
gene expression
Judith E. Mank1, Nina Wedell2 and David J. Hosken2
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Review
Cite this article: Mank JE, Wedell N, Hosken
DJ. 2013 Polyandry and sex-specific
gene expression. Phil Trans R Soc B 368:
20120047.
http://dx.doi.org/10.1098/rstb.2012.0047
One contribution of 14 to a Theme Issue
‘The polyandry revolution’.
1
Department of Genetics, Evolution and Environment, University College London, The Darwin Building,
Gower Street, London WC1E 6BT, UK
2
Centre for Ecology and Conservation, University of Exeter, Cornwall Campus, Tremough, Penryn TR10 9EZ, UK
Polyandry is widespread in nature, and has important evolutionary consequences for the evolution of sexual dimorphism and sexual conflict.
Although many of the phenotypic consequences of polyandry have been
elucidated, our understanding of the impacts of polyandry and mating systems on the genome is in its infancy. Polyandry can intensify selection on
sexual characters and generate more intense sexual conflict. This has consequences for sequence evolution, but also for sex-biased gene expression,
which acts as a link between mating systems, sex-specific selection and
the evolution of sexual dimorphism. We discuss this and the remarkable
confluence of sexual-conflict theory and patterns of gene expression, while
also making predictions about transcription patterns, mating systems and
sexual conflict. Gene expression is a key link in the genotype– phenotype
chain, and although in its early stages, understanding the sexual
selection –transcription relationship will provide significant insights into
this critical association.
Subject Areas:
evolution, genomics
Keywords:
sexual conflict, sexual selection,
gene expression evolution, mating system
Author for correspondence:
Judith E. Mank
e-mail: [email protected]
1. The role of mating and mating system in gene expression
Gene expression represents an important step in the genome–phenotype
relationship in both the short- and long-term. Over the short-term, expression
of many genes is a dynamic response to stimuli, and this is the way that the
static and predefined genome of an individual interacts with changing environments and ecologies over the course of a single lifetime [1,2]. Gene expression
also evolves over time [1,3–5], and adaptive changes in gene expression
represent an important route to phenotypic evolution [6 –8].
Mating system largely defines sex-specific selection, which in turn affects
gene expression patterns in males and females in several different ways. Differences in mating system can generate different intensities of sexual selection and
sex-specific selection, which in turn can generate sexual conflict when males
and females experience different fitness optima for shared traits. It is clear
that sexual conflict often plays out at the genetic level through gene expression
differences between males and females [9,10], as described in table 1. Conflict
can also lead to parent-of-origin genomic imprinting [19,22] when antagonism
between the parents over growth and provisioning plays out through the
developing offspring. Mating system and sex-specific selection also play a
major role in the evolution of sexually dimorphic and sexually selected phenotypes, and many sexually dimorphic traits are encoded by different expression
levels of the same genes rather than by different genes in males and females
[12,23,24], a phenomenon referred to as sex-biased gene expression. In some
extreme cases, expression may be completely absent in one sex leading to
sex-limited gene expression; however, this is relatively rare for genes not
linked to sex-limited Y or W chromosomes [14]. In addition to expressing
different amounts of the same gene, females and males may express different structural arrangements of the same gene, splicing or skipping
different exons to create different protein isoforms [16]. Sex-specific alternate
splicing is common in many animals, and is key to the sex determination
pathway in many insects [15,25,26].
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Table 1. Mechanisms of gene expression differences between males and females.
2
manifestation
prevalence
mechanism
sex-biased
genes expressed in both
very common, may encompass .50% of
sex-biased genes can be regulated by the
gene
expression
sex-limited
gene
females and males, but at
different levels
genes expressed only in
one sex
expression
splicing
imprinting
all Y-linked and W-linked genes are by
definition sex-specific; however, sex-limited
expression is rare aside from these
chromosomes [14]
males and females express
the same genes, but alter
exon order or skip
different exons
either the paternal or
sex determination pathway [12] or sexhormone receptors [13]
for loci present in both sexes, regulation
by Y or W loci could produce sexlimited expression
key element in the sex determination
can occur when splicing is regulated by
pathway in some insects [15]; also
prevalent in mammalian
sex determination pathway or by sexhormone receptors
transcriptomes [16]
involved in sex determination pathway in
presumably, methylation patterns in the
maternal allele is
some insects [17], some medical
parental gametes are maintained in the
expressed in the offspring
conditions [18]; may be common in
mammals [19,20] but this remains
zygote; alternatively, imprinting
requires some sort of sensing
contentious [21]
mechanism to identify parent of origin
Here, we examine how mating and mating system, with
particular emphasis on polyandry, affect gene expression.
Our ultimate aim is to understand the relationship between
the genome, the transcriptome (the sum output of all
expressed genes in an individual) and the phenotype. The
complete attainment of this goal is somewhat distant, as the
connections linking genome, transcriptome and phenotype
remain hazy in many ways; however, initial results have
suggested that gene expression studies may be a powerful
way to study the effects of sexual conflict and sex-specific
selection within the genome. We therefore also extrapolate
from phenotypic data in order to predict how polyandry
might affect gene expression evolution.
2. Short-term gene expression dynamics in
response to courtship and mating
Gene expression is the primary route by which the genome of
an individual responds to environmental, ecological and behavioural stimuli, and so it is perhaps not at all surprising
that mating behaviours and mating itself have large effects
on gene expression. The crucial nature of reproduction, both
in terms of physiology and evolutionary fitness, suggests that
it should factor heavily in gene expression dynamics. Reproductive maturity is associated with a large number of gene
expression changes in both sexes [27–29]. However, sexual
maturity is quite a different physiological state than actual
reproduction, particularly for females in internally fertilizing
species that must assemble either fertilized ova into layableeggs or provision developing embryos. Because courtship
and mating always precede reproduction, these can be thought
of as cues that initiate the final physiological changes required
for successful breeding. From this perspective, courtship- and
mating-induced changes in gene expression are the route by
which an individual begins to transition physiologically from
adult to parent. There are multiple targets and mechanisms
by which courtship behaviour and mating induce transcriptomic changes, and although most of the work in this regard
involves Drosophila, findings there have been corroborated,
albeit with limited evidence from other animals.
There are distinct changes in gene expression that occur in
the brain of males and females related to mating, and these
can be divided into changes relating to mating behaviours
and changes arising owing to mating itself. Visual, auditory
and other courtship cues are alone sufficient to cause gene
expression changes in the female brain, as observed in both
Drosophila melanogaster [30] and songbirds [27,31]. In many
ways, this mirrors recently identified changes in cuticular
hydrocarbon (CHC) bouquets that occur as a consequence
of variation in the social environment and mating status of
male D. melanogaster. CHCs are complex sexual signals in
Drosophila [32], and these plastic expression responses mean
that trait values depend not just on the genotype of focal individuals, but also on the genes being expressed in individuals
that make up the social environment [33,34].
Mating itself causes further gene expression changes in
both male and female brains [35–37]. In all cases, these transcriptomic changes are subtle, and transcriptomic studies in a
range of species suggest sex differences in the brain are relatively modest [13,38 –40]. This may be because small changes
are sufficient to cause large behavioural differences between
the sexes. Alternatively, behaviours are genetically controlled
within relatively confined areas of the brain, and because
these regions are difficult to isolate, studies that have used
whole-brain homogenates almost certainly underestimate
local expression differences [4,40].
Beyond the brain, mating elicits a huge response in gene
expression in the female reproductive tract [37,41,42]. Part
of this is due to the female’s innate transcriptomic preparations for embryo provisioning [43]. In addition to this,
the female reproductive system stages an immune response
Phil Trans R Soc B 368: 20120047
alternative
genes in the genome [11]
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type
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Specific mating systems are associated with different intensities
of sex-specific selection. Selection can alter gene expression or
coding sequence to enact phenotypic change [8,48], and if the
effect of sex-specific selection in coding sequence is anything
to go by [49], then sex-specific selection should also act on
gene expression of loci involved in sexual selection and reproduction. Polyandrous mating systems can experience increased
levels of male-specific selection, particularly in regard to
sperm competition, and this may act on the spermatogenesis
transcriptome in several different ways.
Gene expression differences in males under monandrous
versus polyandrous mating systems are largely unknown,
but we can extrapolate somewhat from the potential for
male-specific selection. Given that polyandry is frequently
associated with increased sperm competition, we might
expect some transcriptomic shift from the production of
somatic sexually selected indicators of male quality in monandrous systems [50] to a greater investment in sperm
production in order to win fertilizations in polyandrous systems [51,52]. This would manifest as higher expression levels
over evolutionary time for genes involved in spermatogenesis, as the sperm production and assembly mechanisms
increase their output in polyandrous versus monandrous
systems. This is not to say that males in polyandrous species
will forgo investment in sexually selected somatic traits
that function in mate choice and competition, but they also
face post-mating competition that requires transcriptional
investment to win. There are two general ways this can be
achieved, either by trade-offs between sexual traits, or by
trading-off sexual traits against other characters. As males
must mate to obtain fitness, we would expect the trade-off
to be with non-sexual traits, and hence polyandrous systems
might display reductions in gene expression levels that have
little obvious connection with sexual fitness. This is consistent
with experimental evolution studies in yellow dung flies
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3. Long-term gene expression evolution in
response to mating system
showing that higher investment in sexual characters such
as testis size under polyandry comes at a cost to immune
function [53 –55].
We might also expect elevated levels of purifying
selection on both the gene sequence and gene expression patterns related to sperm production [56,57]. In mating systems
with no or very little sperm competition, males need only
produce a few viable sperm for each fertilization event.
When the sperm competition that results from polyandry
conforms to a lottery, where sperm are tickets and fertilizations the prize, males will not only be selected to produce
more sperm, but they could also be under selection to produce more high quality sperm to ensure they successfully
fertilize ova [58– 60]. This is clear from experimental evolution studies in mice that show an increase in sperm
quality under polyandrous conditions compared with monogamy [61]. This increase in sperm quality may manifest in
gene expression as lower transcriptional variance for spermatogenesis genes, as variance can be taken as a measure of the
strength of purifying selection on gene expression [4].
The haploid nature of sperm offers the possibility that at
least some genes associated with sperm function are subject
to haploid selection [62]. This would make the effects of purifying selection associated with increased sperm competition
even more powerful, especially for recessive or partially
recessive variation in expression level. However, in metazoans, the scope for haploid selection appears to be relatively
limited [63–65]. This is because DNA compaction during
spermatogenesis means very few genes are expressed solely
by the haploid sperm cell. Instead, expression more often
seems to originate from the testis during sperm formation;
therefore each sperm cell, although carrying a haploid
genome, is composed of proteins from the diploid genotype,
making the sperm population a mix of gene products from
both alleles present in the testes.
The effects of female-specific selection in gene expression
in polyandrous systems are more difficult to predict. Polyandry may result in both post-copulatory and pre-copulatory
mechanisms of female choice in some systems [59], adding
transcriptomic mechanisms of female choice to the reproductive tract. In support of this, a recent study found significant
differences in expression levels of ovary and brain genes in
female D. melanogaster mated to either preferred or unpreferred males, indicating the involvement of both pre- and
post-copulatory female choice mechanisms [66]. Beyond
that, female-specific selection to reduce polyspermy may
drive the evolution of gamete-recognition proteins on the
ovum [67– 69].
As with males, polyandry could cause shifts in the focus of
female choice to the post-copulatory arena at a cost to pre-copulatory mechanisms of choice, but selection could also favour
reductions in investment elsewhere while retaining pre- and
expanding post-copulatory choice mechanisms. This may
also depend on how easy it is for females to avoid multiple
mating when it is not in females’ interests. Again, experimental
evolution has shown that females’ ability to circumvent male
interests evolves under polyandry and that this comes at a
cost to non-sexual immunological fitness [52,70]. Further
support for the suggestion that females may divert their
investment towards post-copulatory mechanisms comes from
evidence that sperm storage can represent a cost to females,
again in terms of compromised immune response. In Atta
columbiana ants, for example, sperm storage is traded off
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to the foreign proteins contained in the male’s seminal
fluid [43– 45]. Finally, part of the changes in the female
reproductive tract is in response to manipulative proteins
from the male transcriptome in the form of accessory gland
proteins (ACPs) [41,46,47], which stimulate female oogenesis
and ovulation, as well as impede female remating [47].
ACPs appear to be involved in inter-locus sexual conflict,
which involves interactions between antagonistic alleles at
two or more loci in males and females, and so they are also
discussed in §6.
Most studies of gene expression in relation to mating
compare mated and unmated individuals, and so therefore
cannot differentiate the effects of monandry from polyandry
in the female reproductive tract. Initial evidence suggests that
female transcriptomic responses to multiple mating are not
cumulative, rather the majority of changes occur with the transition from virgin to non-virgin, and additional matings after
the first do little to change the female transcriptome further
[45]. However, there may be a temporal aspect to polyandryinduced changes to the female transcriptome. Single-mated
females experience a transcriptomic cycle extending for several
hours after mating [42], and polyandrous females may
experience this cycle multiple times.
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Although polyandry can potentially reduce the variance in
male reproductive success, and thereby reduce the intensity
of sexual selection [73 –75], in many cases the evolution of
polyandry also brings with it greater potential for interlocus and intra-locus sexual conflict between females and
males compared with monogamy. This sexual conflict can
play out between the parents directly as males and females
seek to manipulate each other’s reproduction. Inter-locus
conflict, which involves antagonistic alleles at multiple loci,
includes maternal–foetal conflict over resource provisioning
in species with internal gestation. Intra-locus conflict, where
alleles at a single locus influence male and female fitness in
opposite directions can affect a large proportion of the
genome [76], and influences gene expression in several
ways, ranging from transcriptional differences between the
sexes [9,77– 79] to parent-of-origin imprinting in the developing offspring [80,81]. At this point, there are few direct
connections between gene expression and sexual conflict,
although it is becoming increasingly possible to test the existing predictions [77,81,82] with transcriptome data [19,78,79].
What is lacking most is the direct connection between transcriptome data and sex-specific phenotypes, but that will
no doubt emerge in time.
5. Mechanisms of differential gene expression
Phenotypes are ultimately composed of protein, and many
phenotypic differences are attributable to differences in
protein levels [8,48]. The same is true of sex-specific phenotypes, many of which are the result of differential gene
expression between males and females, and ultimately
many of these must result from conflicting selection between
the sexes. Transcription of RNA is a direct predictor of
protein translation levels, and because protein chemistry is
much more difficult to work with than RNA chemistry, it is
often easier to use RNA levels as a proxy for protein levels.
Although the same nuclear genome is present in every
somatic cell of an organism, the transcriptome is far more
variable, and can vary throughout the body and over a life
cycle. This is particularly true for sex-specific transcriptomes,
which differ during development [29,83] and among different tissues in the body [84– 86]. Transcriptome studies must
therefore target the correct part of the body and the correct
developmental stage.
Developmental stage is particularly important in this context, because although sexual dimorphisms and sexually
selected phenotypes are most evident in adults, a significant
proportion of these traits are the product of developmental
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4. Polyandry and the effects of increased
sexual conflict
processes that amplify into adult phenotypes. For example,
the horn in adult male horned beetles is the product of
larval differences between the sexes that increase over development [23,87,88]. Similarly, the transcriptomic basis of the
sword in male swordtails is largely complete by the time
the sword manifests fully in the adult phenotype [24]. In
cases such as these, it is crucial to sample the individual at
the stage at which sexual dimorphisms are being programmed in the phenotype, rather than the adult stage
when the dimorphism is simply most evident.
There are several routes by which males and females can
express the same gene in different ways and therefore achieve
sex-specific phenotypes (table 1). Sex-biased expression is the
most commonly assayed form of gene expression differences,
and it is clear that many, if not most genes, are expressed at
different levels between the sexes at some point in development or in some part of the body [89]. Aside from genes on
sex-limited Y or W chromosomes, addressed later, relatively
few of these differences are due to sex-limitation, where a
gene is completely shut off in one sex or the other. Rather,
most sex-biased gene expression is the product of different
transcription rates of genes expressed to some degree in
both males and females. The rarity of sex-limited expression
may be due to the fact that selection to shut off expression
progressively weakens as gene expression decreases and
therefore produces little phenotypic effect. Theoretically, the
difference in transcription between females and males is
due to sexual conflict over optimal protein levels [9], and
this conflict can be resolved when the correlation in
expression between the sexes is broken down.
It is, however, not always possible to resolve sexual
conflict, especially when there are ontogenetic [90] or pleiotropic [91] constraints acting on a sexually antagonistic
locus. It may be that in these cases, recent gene duplicates
take on sex-specific expression patterns [92,93]. Gene duplication may therefore represent a route to the resolution of
conflict over genes that perform multiple functions [82,92],
but this may also require modifications to genetic architecture
[94], in addition to dominance, recombination, sex-linkage
and population size [82].
Although there are reasons to think that this might not
be an easy or common solution to sexual conflict [95], gene
expression studies, particularly of the sex chromosomes,
have demonstrated that gene duplication, and duplicationmediated relocation, can provide a route for sexually
antagonistic loci to transfer to regions of the genome with
beneficial sex-specific selection regimes. The best illustrations
come from the sex-limited W and Y chromosomes, which,
due to their sex-limited nature, experience only femalespecific (in the case of the W) or male-specific (in the case
of the Y) selection. Female-benefit genes that cause harm to
males relocating to the W chromosome, or present on
newly emergent W chromosomes, may experience the
immediate resolution of this conflict as these genes are no
longer expressed in males, and the same is true for malebenefit genes on Y chromosomes [96]. However, relocation
to the Y or W chromosome, associated with loss of the
original autosomal, X- or Z-linked locus, will resolve conflict
only for some types of genes, particularly those with narrow
sex-specific functions, and will not resolve conflicts over optimal expression for genes that function in both sexes. For the
latter class of genes, resolution can occur via duplication to
the Y and W chromosomes followed by sex-specific
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against the ability to mount an immune response, and this
effect is exacerbated when the ejaculates from different males
are stored, possibly indicating an increased cost of storing
and processing genetically different ejaculates [71]. In Drosophila pseudoobscura, a species with polymorphic sperm, nonfertile sperm function to protect the fertile sperm against
female-mediated sperm death [72]. Female spermicide in
turn may have evolved as a mechanism to reduce the cost of
storing sperm from several males.
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(a)
(b)
relocation
5
duplication
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autosomes
X or Z
chromosome
Y or W
chromosome
autosomes
X or Z
chromosome
Figure 1. Duplication or relocation to the Y or W chromosome can resolve sexual conflict. (a) For genes that do not affect phenotypes in both sexes, relocation to
the Y or W chromosome leads to sex-limited expression, there is no mutation accumulation in the non-expressing sex, and expression from the parent locus ceases
after relocation. (b) In those cases where a sexually antagonistic gene is involved in both male and female phenotypes, duplication to the Y or W chromosome can
lead to sex-specific divergence of the daughter locus and the parent locus can be retained. It is currently not clear, however, how long it takes for gene associations
(genetic architecture) involving the parent gene to disconnect from the daughter locus.
specialization of the W- or Y-linked daughter locus, in concert with retention of the parental copy (figure 1). This
route may be more common than relocation for genes with
many network connections or multiple functions. Selection
for sexual conflict resolution may drive the evolution and
turnover of sex chromosome systems [97,98], as well as
gene gain by existing sex chromosomes, as evidenced by
the fact that the rate of gene acquisition on the Drosophila Y
chromosome is nearly ten times greater than the rate of
gene loss [99]. We discuss the more complex pattern expected
and observed for Z and X chromosomes in §7.
It is not clear at this point how common sexual conflict is
at the level of the exon versus the entire transcribed gene;
however, there is growing evidence that males and females
do not just express genes at different levels, but they also
splice many genes differently, combining exons in different
order or combinations. Sex-specific alternate splicing is
common for many genes [16], and although alternate splicing
is key to the sex determination pathway in many insects
[15,25,26], it is not yet clear how alternative splicing contributes to somatic phenotypic sexual dimorphisms or sexual
conflict in a broader sense.
Genomic imprinting occurs when maternally or paternally
inherited copies of a gene are expressed differently in the offspring, presumably due to methylation of genes or other
regulatory control. Imprinting of single loci is important in
the sex determination pathways of some haplodiploid insects
[17,100], and recent assessments have suggested that imprinting affects a large proportion of mammalian genes [19,20],
although the veracity of these results is currently under intense
debate [21]. If this mechanism is common, it may represent
a means of resolving sexual conflict that plays out in the
developing offspring [81].
6. Inter-locus sexual conflict
Inter-locus sexual conflict can generate an arms race of
adaptation and counter-adaptation in males and females
that can result in severe physiological costs [101], as well as
spurring phenotypic evolution [102]. Inter-locus sexual conflict is somewhat difficult to study from a gene expression
perspective without some prior knowledge of the loci
involved, although work on ACPs and imprinted loci provide
some ideas about how the transcriptome may be affected. It
may be that increasing levels of sexual conflict under polyandry mean that a greater proportion of loci become entangled
in inter-locus arms races between males and females compared with monogamy. However, it may be some time yet
before a comprehensive catalogue of the genomic distribution
of loci involved in this type of conflict is available. In the
meantime, there are several illustrative examples.
Given their role in sexual conflict, the genes encoding
ACPs represent potential loci for male benefits in the sexually
antagonistic coevolution that can be associated with polyandry. When present in an ejaculate, ACPs act to manipulate
female reproduction in the male’s favour and impede
female remating [47]. They are therefore subject to particularly strong male-specific selection, which may explain why
ACPs are among the most rapidly evolving proteins in the
genome [103,104]. Females show a profound transcriptomic
response to ACPs [41,46,47], and female-specific selection
could act to make females resistant to male manipulation
that is harmful to female fitness. Because of this, we might
predict that ACPs would evolve more rapidly under polyandry than both monandry and monogamy. Although
polyandry is associated with increased rates of evolution of
seminal fluid proteins in primates [105], this pattern is not
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Y or W
chromosome
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Intra-locus sexual conflict occurs when an allele at a single
locus moves one sex away from its fitness optima but the
other sex towards its sex-specific fitness peak [116], and has
been documented in many traits and species [117]. However,
while inter-locus sexual conflict can produce unresolvable
arms races, the potential for resolution may be greater for
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7. Intra-locus sexual conflict and the evolution of
sex-biased gene expression
intra-locus sexual conflict. Resolution of intra-locus sexual
conflict was thought to occur when the genetic correlation
between males and females was broken down, allowing for
the evolution of phenotypic sexual dimorphism [77,118].
However, it has become apparent that things are not as
straightforward as this [119], primarily because genes do
not exist in isolation of other genes. The network and interactive structure of genetic pathways means that selection on a
sex-limited gene can still ripple through the genome, and
mutations will still accumulate in the sex lacking expression
because they are neutral, and these could keep the expressing
sex from reaching a fitness optimum [81,94]. For example,
recent artificial selection work on the broad-horned flour
beetle has shown how selection on a male-limited trait
alters female fitness, because the male sex-limited trait is
genetically correlated to other traits, and these in turn are
genetically correlated between the sexes [90]. As a result,
selecting on the male-limit trait, the mandibles, reverberates
throughout the genetic network, ultimately affecting female
fitness, and although females never develop mandibles, it is
this sex-limited trait that lies at the heart of the sexual conflict.
Intra-locus sexual conflict over gene expression may therefore
not be resolved simply by the evolution of sex-biased or
sex-limited gene expression. Furthermore, while it is now
possible to measure transcriptomic differences between the
sexes to identify a measure of intra-locus sexual conflict
within the genome [78], it is not clear whether these differences
completely or only partially resolve conflicts.
Despite these concerns, sex-biased gene expression represents possibly the most direct connection linking sexual
conflict, mating system and the evolution of sexual dimorphism with the genome, and although work on this front has
been possible for little more than a decade, it is surprising
how well sex-biased gene expression patterns conform to
the predictions from intra-locus sexual conflict theory. For
example, the greatest degree of sex-bias is observed in gonad
transcriptomes [85,86,89], as is expected given the profound
degree of conflict between optimal male and female gamete
production and provisioning strategies. Male and female
gonad formation and gametogenesis involve many of the
same genes used in different ways, and this makes the testis
and the ovary the site of maximal sexual conflict within the
body. Sex-biased genes, as the encoding loci underlying
sex-specific phenotypes, experience the accelerated rates of
evolution predicted by sexual selection [11,120,121].
Furthermore, gene expression patterns on the X and
Z sex chromosomes show evidence of sex-specific selection
[10,79,122], as predicted by their uneven inheritance between
males and females [77,123]. Although the pattern is complicated
by the effects of sex chromosome regulation related to meiotic
sex chromosome inactivation and dosage compensation [122],
a general pattern emerges. X chromosomes are more often
present in females than males, and therefore more often selected
for female-specific effects. This has been tested with gene
expression data with the assumption that female-biased genes
benefit females and male-biased genes benefit males. Under
this framework, the finding that the X chromosomes in both
the mouse and Drosophila harbour a combination of excessive
female-biased genes and fewer than expected male-biased
genes [124] fits with sexual conflict predictions. These observations are supported by a recent population genetic model,
showing that female-biased gene duplications preferentially
accumulate on the X chromosome [77].
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universal, and polyandry does not explain rates of sequence
evolution for ACPs in Heliconius butterflies [106,107]. It may
be that polyandry does not affect sequence evolution as
much as expression level of ACPs because increasing female
resistance may select for increased ACP dosage. Alternatively,
inter-locus sexual conflict may result in high turnover of ACPs.
This would occur if males do not refine their existing toolkit
with which they try to manipulate females, but instead exploit
entirely new mechanisms that result in male fitness benefit and
female cost. This may explain the vast number of ACPs in
D. melanogaster (more than 100). Finally, it may be that other
aspects of the ejaculate are responsible for suppressing
female receptivity. In butterflies, for example, non-fertile
sperm inhibit female remating by filling the female’s spermstorage organ [108], and male harming of females during
copulation is in theory another way to suppress remating
[109]. Finally, ACPs may also be beneficial to females when
acting as nutrient provisioning. This can still generate sexual
conflict over female receptivity, and there is evidence in butterflies that there is extensive genetic variation and genetic
correlations between the sexes for ability to suppress female
receptivity in males and to withstand manipulation in females
[110], although whether this is due to differences in expression
level or gene sequences remains to be examined.
The increased level of inter-locus sexual conflict associated
with polyandry may in some cases target alleles based on their
parent of origin. There is a large body of evolutionary theory
that predicts that sexual conflict will foster genomic imprinting
[80,81,111–113], where either the maternal or paternal allele
at a given locus is expressed in the offspring rather than
normal bi-allelic expression. Imprinting of this form allows
conflict between the parents to play out in the offspring, and
has been shown to be particularly important in foetal growth
[18] and murine mating behaviour [114], and underlie sex
determination in scale insects [115].
Given the increased potential for inter-locus sexual conflict
under polyandry, we might expect to observe a greater proportion of imprinted loci within the genome in polyandrous
lineages compared with monogamous species. Until recently,
however, surveying whole genomes for imprinted loci was difficult, and although the recent development of methods to scan
for allelic imbalance in transcriptomic data may facilitate
genome-wide surveys [19,20], this method is not without
serious concern [21]. Additionally, there are methods that
search RNA data for imprinting by looking for any statistical
deviation from bi-allelic expression no matter how slight,
and it is unclear how much of this effect is due to variation in cis-regulatory regions that affect expression versus
conflict-driven selection for parent-of-origin imprinting. Most
importantly, it is not clear how biologically relevant slight
deviations from bi-allelic expression are, or how they might
manifest phenotypically.
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8. Conclusions
The recent exponential advances in sequencing capability
and reduced cost make the genome and the transcriptome
approachable scientific frontiers for the study of model
and non-model organisms alike. At the moment, there is a
7
Phil Trans R Soc B 368: 20120047
greater magnitudes of expression difference. Whether
greater levels of sexual dimorphism are due to more sexbiased genes or a few genes with greater magnitude of
sex-bias depends on how much of the genome is subject to
sexual conflict, and to a lesser extent, how much conflict
can be resolved via differential expression levels. Similar predictions might be expected to hold for sex-specific alternate
splicing, as this is really an exon-specific form of sex-biased
gene expression.
If the elevated rates of sequence evolution observed for sexbiased genes [89,120,121] really are the product of sex-specific
selection, then we might expect the relative rates of evolution
for sex-biased genes to be higher in polyandrous than monogamous systems. Relative rates of evolution for sex-biased genes
under different mating systems may need to be determined
in adults and embryos separately, as evidence from birds
suggests that male-specific selection is strongest on adultexpressed genes while female-specific selection acts maximally
on late-embryonic-expressed genes [29]. This is also consistent with studies at the phenotypic level in Drosophila where
there is evidence of ontogenetic conflict between males and
females [132].
Additionally, if sex chromosomes really are a hotspot of
sexually antagonistic selection [10,77,123], then the increased
conflict that results from those forms of polyandry might be
expected to feminize X chromosomes and masculinize Z
chromosomes to a greater degree than in monogamous or
monandrous species. If this is true, it would potentially be
demonstrated via greater levels of female-biased expression on X chromosomes and male-biased expression on Z
chromosomes, and faster rates of gene exodus for malebiased genes from the X and female-biased genes from the Z
chromosomes. At this point, these predictions are simple
hand-waving based on vague assumptions, but hopefully
they will soon be tested critically by studies that span clades
with varying mating systems.
A phylogenetic approach will also help determine the
time-scale of sex-specific transcriptome evolution. Shortterm sex-specific experimental evolution in Drosophila
produced little change in sex-biased expression [78]; however, sex-bias varies in both domestic animal breeds that
have been subject to sex-specific selection regimes for more
than 100 generations [14], and among closely related species
[131]. This suggests that transcriptional evolution can occur
for many genes over medium- and long-term evolutionary
distances, and a phylogenetic study of closely related species
with different mating systems will help quantify the rate of
sex-specific transcriptomic evolution in response to defined
sex-specific selection. This will help answer questions regarding the response mechanisms as well. For example, does the
elevated level of sexual conflict in polyandrous systems
mean that sex-biased expression evolves more rapidly than
in monogamous species? Does polygamy produce more
sex-biased genes, or does it produce a greater magnitude of
sex-bias in a relatively small number of genes?
rstb.royalsocietypublishing.org
Several objections to the approach of employing sexbiased gene expression to study sexual conflict have been
voiced [94,125], including potential limitations of sex-specific
regulatory mechanisms and differential male and female allometry. The first concern arises because very few genes lie
directly in the sex determination pathway or are proximately
located to sex-hormone receptors. This might suggest that
there is very little scope for sex-specific gene regulation.
However, there is clear evidence that sexual dimorphism of
somatic traits can result when gene expression of the trait is
ultimately regulated by the sex determination pathway
[12,126,127]. Additionally, there are several thousand oestrogen and testosterone receptors in the average metazoan
genome [128,129], and the interactive nature of the genetic
network implies that even if only a few hundred genes are
under direct control of sex hormones, they can transmit sexbiased expression through to thousands of other genes
under their regulatory control. This suggests that the potential for sex-specific gene regulation is extensive, if not
limitless. It also suggests that the complete resolution of
sexual conflict may be difficult because of these extensive
gene networks.
Additionally, initial studies of sex-biased gene expression
were performed on whole animals [120,121], leading to
concerns that sex-biased expression was a result of different
sex-specific allometry of constituent body parts. However,
the opposite has been observed, as whole-body and aggregate transcriptome studies actually underestimate the
degree of sex-bias within constituent parts [40,85,86]. This is
particularly problematic for studies of brain transcription:
although fine scale analysis of gene expression in the brain
has revealed profound sex-bias in limited areas that control
sex-specific behaviours [130], whole-brain or partial-brain
homogenates reveal very little overall sex-bias [39,40] because
sex-specific expression of different genes in different regions
is averaged, and localized differences are therefore diluted.
This suggests that the initial estimates of whole-body sexbias in roughly half of all genes are in fact underestimates,
rather than overestimates, and that finer-scale dissections
will reveal more pervasive patterns of local sex-biased
gene expression.
With these concerns allayed, we can now move on to discussing how polyandry influences sex-biased gene expression
in light of intra-locus sexual conflict. The short answer is that
we have no idea, and this is because no one has yet directly compared monogamous, monandrous and polyandrous species in
a phylogenetically controlled study. At this point, we know
that sex-biased expression varies among species [131], but this
has not yet been put into the context of mating system.
Simply doing so, ideally comparing related species with different mating systems, would be a big step. In the absence of
any solid data, we can only speculate wildly.
Sex-specific selection and sexual conflict may be stronger
in polyandrous than monogamous systems. This is because
even under polyandry, a few males more or less monopolize
paternity. We therefore expect that phenotypic sexual
dimorphism will either be greater in magnitude, or possibly
just evolve more quickly, under polyandry compared with
monogamy. If protein abundance, and therefore transcription level, holds the key to sexually dimorphic phenotypes,
then we might expect either sex-biased gene expression
to be prevalent in a larger proportion of genes under polyandry, or alternatively, a limited number of genes will show
Downloaded from http://rstb.royalsocietypublishing.org/ on June 17, 2017
sexual conflict, mating system and the evolution of sexual
dimorphism with the genome.
The rapid expansion of the research frontier in sexual
selection and sexual conflict is exciting, and it creates
opportunities for both theoretical frameworks for gene
expression evolution, as well as empirical tests in a range of
organisms with interesting mating systems. Stay tuned for
forthcoming developments.
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Phil Trans R Soc B 368: 20120047
Work in J.E.M.’s laboratory is supported by the BBSRC and the ERC
(grant agreement no. 260233); N.W. by a Royal Society Wolfson Merit
Award and NERC, and D.J.H. was supported by NERC. We thank
the Editors for the invitation to participate in this special issue and the
Royal Society for supporting the process. We also thank two anonymous
referees for comments, which helped improve the manuscript.
8
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