Sexually antagonistic epigenetic marks that canalize sexually dimorphic development.

The sexes share the same autosomal genomes, yet sexual dimorphism is common due to sex-specific gene expression. When present, XX and XY karyotypes trigger alternate regulatory cascades that determine sex-specific gene expression profiles. In mammals, secretion of testosterone (T) by the testes during foetal development is the master switch influencing the gene expression pathways (male vs. female) that will be followed, but many genes have sex-specific expression prior to T secretion. Environmental factors, like endocrine disruptors and mimics, can interfere with sexual development. However, sex-specific ontogeny can be canalized by the production of epigenetic marks (epimarks) generated during early ontogeny that increase sensitivity of XY embryos to T and decrease sensitivity of XX embryos. Here, we integrate and synthesize the evidence indicating that canalizing epimarks are produced during early ontogeny. We will also describe the evidence that such epimarks sometimes carry over across generations and produce mosaicism in which some traits are discordant with the gonad. Such carryover epimarks are sexually antagonistic because they benefit the individual in which they were formed (via canalization) but harm opposite-sex offspring when they fail to erase across generations and produce gonad-trait discordances. SA-epimarks have the potential to: i) magnify phenotypic variation for many sexually selected traits, ii) generate overlap along many dimensions of the masculinity/femininity spectrum, and iii) influence medically important gonad-trait discordances like cryptorchidism, hypospadias and idiopathic hirsutism.

Homosexuality via canalized sexual development: a testing protocol for a new epigenetic model.

We recently synthesized and reinterpreted published studies to advance an epigenetic model for the development of homosexuality (HS). The model is based on epigenetic marks laid down in response to the XX vs. XY karyotype in embryonic stem cells. These marks boost sensitivity to testosterone in XY fetuses and lower it in XX fetuses, thereby canalizing sexual development. Our model predicts that a subset of these canalizing epigenetic marks stochastically carry over across generations and lead to mosaicism for sexual development in opposite-sex offspring--the homosexual phenotype being one such outcome. Here, we begin by outlining why HS has been under-appreciated as a commonplace phenomenon in nature, and how this trend is currently being reversed in the field of neurobiology. We next briefly describe our epigenetic model of HS, develop a set of predictions, and describe how epigenetic profiles of human stem cells can provide for a strong test of the model.

Partitioning sexual selection into its mating success and fertilization success components.

Postcopulatory sexual selection due to sperm competition and/or cryptic female choice has been documented in a diversity of taxonomic groups and is considered a pivotal component of sexual selection. Despite this apparent importance, the relative contribution of postcopulatory fertilization success to overall sexual selection has not yet been measured in any species. Here, we used a laboratory-adapted population of the promiscuous fruit fly Drosophila melanogaster to partition the variance in male reproductive success into mating success (a major component of precopulatory sexual selection) and fertilization success (a major component of postcopulatory sexual selection). We found that fertilization success contributed nearly as strongly as mating success to a male's net performance in sexual selection, but that most of this postcopulatory component was attributable to variation in male mating order (the tendency to be the last male to mate a female). After adjusting for mating order, only ≈2% of the residual variation in male reproductive success was attributable to differential fertilization success. We found no correlation between male mating success and fertilization success in this system. Unlike natural populations of Drosophila, our laboratory population is adapted to a semelparous lifecycle, so our findings will be most applicable to other promiscuous species with strong sperm precedence and one short breeding period per year or lifetime. In these species, fertilization success may have as much influence on male reproductive success as mating success, but the timing of mating (mating order) may be the predominant factor contributing to variation in fertilization success.

Population-based resequencing of experimentally evolved populations reveals the genetic basis of body size variation in Drosophila melanogaster.

Body size is a classic quantitative trait with evolutionarily significant variation within many species. Locating the alleles responsible for this variation would help understand the maintenance of variation in body size in particular, as well as quantitative traits in general. However, successful genome-wide association of genotype and phenotype may require very large sample sizes if alleles have low population frequencies or modest effects. As a complementary approach, we propose that population-based resequencing of experimentally evolved populations allows for considerable power to map functional variation. Here, we use this technique to investigate the genetic basis of natural variation in body size in Drosophila melanogaster. Significant differentiation of hundreds of loci in replicate selection populations supports the hypothesis that the genetic basis of body size variation is very polygenic in D. melanogaster. Significantly differentiated variants are limited to single genes at some loci, allowing precise hypotheses to be formed regarding causal polymorphisms, while other significant regions are large and contain many genes. By using significantly associated polymorphisms as a priori candidates in follow-up studies, these data are expected to provide considerable power to determine the genetic basis of natural variation in body size.

The evolution of an enigmatic human trait: false beliefs due to pseudo-solution traps.

In this essay I ask why it is so common for people to hold strong beliefs despite insufficient evidence to justify them. I approach this question from an evolutionary perspective of ultimate causation rather than a neurophysiological perspective of proximate causation. Beginning with simple optical illusions, I use a progression of examples to argue that humans are programmed to form false beliefs due to (i) intrinsic errors of intuition and, more importantly, (ii) a propensity to accept intuitively compelling beliefs without sufficient evidence when they appear to provide solutions to problems that cannot be solved with available knowledge. The formation of these false beliefs and their persistence constitute a phenomenon I call a pseudo-solution trap. I show that these mental traps are especially prevalent in the area of medicine. I end by showing that pseudo-solution traps are expected to feasibly lead to a belief in the supernatural, including an afterlife and one or more deities.

A cost of sexual attractiveness to high-fitness females.

Adaptive mate choice by females is an important component of sexual selection in many species. The evolutionary consequences of male mate preferences, however, have received relatively little study, especially in the context of sexual conflict, where males often harm their mates. Here, we describe a new and counterintuitive cost of sexual selection in species with both male mate preference and sexual conflict via antagonistic male persistence: male mate choice for high-fecundity females leads to a diminished rate of adaptive evolution by reducing the advantage to females of expressing beneficial genetic variation. We then use a Drosophila melanogaster model system to experimentally test the key prediction of this theoretical cost: that antagonistic male persistence is directed toward, and harms, intrinsically higher-fitness females more than it does intrinsically lower-fitness females. This asymmetry in male persistence causes the tails of the population's fitness distribution to regress towards the mean, thereby reducing the efficacy of natural selection. We conclude that adaptive male mate choice can lead to an important, yet unappreciated, cost of sex and sexual selection.

X- and Y-chromosome linked paternal effects on a life-history trait.

Males and females usually invest asymmetrically in offspring. In species lacking parental care, females influence offspring in many ways, while males only contribute genetic material via their sperm. For this reason, maternal effects have long been considered an important source of phenotypic variation, while paternal effects have been presumed to be absent or negligible. The recent surge of studies showing trans-generational epigenetic effects questions this assumption, and indicates that paternal effects may be far more important than previously appreciated. Here, we test for sex-linked paternal effects in Drosophila melanogaster on a life-history trait, and find substantial support for both X- and Y-linked effects.

Male genotype influences female reproductive investment in Drosophila melanogaster.

In many species, males can influence the amount of resources their mates invest in reproduction. Two favoured hypotheses for this observation are that females assess male quality during courtship or copulation and alter their investment in offspring accordingly, or that males manipulate females to invest heavily in offspring produced soon after mating. Here, we examined whether there is genetic variation for males to influence female short-term reproductive investment in Drosophila melanogaster, a species with strong sexual selection and substantial sexual conflict. We measured the fecundity and egg size of females mated to males from multiple isofemale lines collected from populations around the globe. Although these traits were not strongly influenced by the male's population of origin, we found that 22 per cent of the variation in female short-term reproductive investment was attributable to the genotype of her mate. This is the first direct evidence that male D. melanogaster vary genetically in their proximate influence on female fecundity, egg size and overall reproductive investment.

Sexually antagonistic "zygotic drive" of the sex chromosomes.

Genomic conflict is perplexing because it causes the fitness of a species to decline rather than improve. Many diverse forms of genomic conflict have been identified, but this extant tally may be incomplete. Here, we show that the unusual characteristics of the sex chromosomes can, in principle, lead to a previously unappreciated form of sexual genomic conflict. The phenomenon occurs because there is selection in the heterogametic sex for sex-linked mutations that harm the sex of offspring that does not carry them, whenever there is competition among siblings. This harmful phenotype can be expressed as an antagonistic green-beard effect that is mediated by epigenetic parental effects, parental investment, and/or interactions among siblings. We call this form of genomic conflict sexually antagonistic "zygotic drive", because it is functionally equivalent to meiotic drive, except that it operates during the zygotic and postzygotic stages of the life cycle rather than the meiotic and gametic stages. A combination of mathematical modeling and a survey of empirical studies is used to show that sexually antagonistic zygotic drive is feasible, likely to be widespread in nature, and that it can promote a genetic "arms race" between the homo- and heteromorphic sex chromosomes. This new category of genomic conflict has the potential to strongly influence other fundamental evolutionary processes, such as speciation and the degeneration of the Y and W sex chromosomes. It also fosters a new genetic hypothesis for the evolution of enigmatic fitness-reducing traits like the high frequency of spontaneous abortion, sterility, and homosexuality observed in humans.

The evolution of sex-specific grandparental harm.

Recent empirical studies indicate that grandparents favour some categories of grandchildren over others. Here, we expand the previous theoretical foundation for this finding and show that grandchild-harming phenotypes are predicted to evolve by 'sexually antagonistic zygotic drive (SA-zygotic drive) of the sex chromosomes'. We use the logic of Hamilton's rule to develop a new 'no-cost-to-self nepotism rule' that greatly simplifies the determination of the invasion criteria for mutations that cause grandparents to harm grandchildren. We use this theory to generate predictions that distinguish SA-zygotic drive from theory based solely on paternity assurance. The major diagnostic prediction is that grandmothers, and to a lesser degree grandfathers, will evolve grandson-harming phenotypes that reduce the level of sib competition experienced by their more closely related granddaughters, especially in their sons' families. This prediction is supported by data from recent studies showing (i) grandmothers invest more in granddaughters than grandsons, and counterintuitively, (ii) paternal grandmothers reduce the survival of their grandsons. We conclude that SA-zygotic drive is plausibly operating in humans via sexually antagonistic grandparental care.

Resolving intralocus sexual conflict: genetic mechanisms and time frame.

Intralocus sexual conflict occurs due to the expression of sexually antagonistic alleles: those that increase fitness when expressed in one sex but decrease fitness when expressed in the other sex. This genetic conflict is expected whenever the sexes are selected toward differing phenotypic optima for a trait that has a positive genetic correlation between the sexes. Here we synthesize recent developments in the areas of genomics, microarray analysis, and developmental and molecular genetics to establish feasible mechanisms by which the intersexual genetic correlation can be reduced, as well as the time course over which conflict resolution is expected to evolve.

Cut thy neighbor: cyclic birth and death of recombination hotspots via genetic conflict.

Most recombination takes place in numerous, localized regions called hotspots. However, empirical evidence indicates that nascent hotspots are susceptible to removal due to biased gene conversion, so it is paradoxical that they should be so widespread. Previous modeling work has shown that hotspots can evolve due to genetic drift overpowering their intrinsic disadvantage. Here we synthesize recent theoretical and empirical results to show how natural selection can favor hotspots. We propose that hotspots are part of a cycle of antagonistic coevolution between two tightly linked chromosomal regions: an inducer region that initiates recombination during meiosis by cutting within a nearby region of DNA and the cut region itself, which can evolve to be resistant to cutting. Antagonistic coevolution between inducers and their cut sites is driven by recurrent episodes of Hill-Robertson interference, genetic hitchhiking, and biased gene conversion.

Sexually antagonistic chromosomal cuckoos.

The two kinds of sex chromosomes in the heterogametic parent are transmitted to offspring with different sexes, causing opposite-sex siblings to be completely unrelated for genes located on these chromosomes. Just as the nest-parasitic cuckoo chick is selected to harm its unrelated nest-mates in order to garner more shared resources, sibling competition causes the sex chromosomes to be selected to harm siblings that do not carry them. Here we quantify and contrast this selection on the X and Y, or Z and W, sex chromosomes. We also develop a hypothesis for how this selection can contribute to the decay of the non-recombining sex chromosome.

Arrest of sex-specific adaptation during the evolution of sexual dimorphism in Drosophila.

Sexually antagonistic selection arises when a trait expressed in both sexes (a shared trait) is selected towards different, sex-specific optima. Sex-discordant selection causes different alleles to be favoured in each sex (intralocus sexual conflict). A key parameter responsible for generating this conflict is the intersexual genetic correlation (rMF), which determines the degree to which heritable genetic variation for the shared trait produces a similar phenotype in both sexes. A strong, positive rMF interferes with adaptation when there is sex-discordant selection. In principle, the rMF can evolve in response to sex-discordant selection: the faster it declines, the faster the resolution of intralocus sexual conflict. Here, we use Drosophila melanogaster to quantify the time scale over which a strong, positive rMF impedes a response to sex-discordant selection for a canonical quantitative trait (body size) with an exceptionally long (250 generations) selection experiment for a complex multicellular organism. We found that, compared with rapid and substantial evolution under sex-concordant selection, a high rMF arrested sex-specific adaptation for 100 generations in females and a minimum of 250 generations in males. Our study demonstrates that a high rMF can lead to a protracted period of adaptive stalemate during the evolution of sexual dimorphism.

An assessment of sperm survival in Drosophila melanogaster.

Recently published evidence based on cytological staining indicates that sperm die rapidly after being stored in female Drosophila melanogaster. However, measuring sperm death in this way has a potential artifact: the death of sperm owing to the extraction, mounting, and staining of sperm. Here we use a protocol that bypasses all of these potential extraneous mortality factors to test the hypothesis that there is high mortality of stored sperm in D. melanogaster. Contrary to the findings from cytological staining, our data indicates that mortality of stored sperm is quite low.

Adult locomotory activity mediates intralocus sexual conflict in a laboratory-adapted population of Drosophila melanogaster.

The strongest form of intralocus sexual conflict occurs when two conditions are met: (i) there is a positive intersexual genetic correlation for a trait and (ii) the selection gradients on the trait in the two sexes are in opposite directions. Intralocus sexual conflict can constrain the adaptive evolution of both sexes and thereby contribute to a species' 'gender load'. Previous studies of adult lifetime fitness of the same sets of genes expressed in both males and females have established that there is substantial intralocus conflict in the LHM laboratory-adapted population of Drosophila melanogaster. Here, we investigated whether a highly dimorphic trait-adult locomotory activity-contributed substantially to the established intralocus sexual conflict. To measure the selection gradient on activity level, both this trait and adult lifetime fitness were measured under the same environmental conditions to which the flies were adapted. We found significant phenotypic variation in both sexes for adult locomotory activity, and that the selection gradients on this variation were large and in opposite directions in the two sexes. Using hemiclonal analysis to screen 99% of the entire genome, we found abundant genetic variation for adult locomotory activity and showed that this variation occurs on both the X and autosomes. We also established that there is a strong positive intersexual genetic correlation for locomotory activity. These assays revealed that, despite the strong, extant sexual dimorphism for the trait, locomotory activity continues to contribute strongly to intralocus sexual conflict in this population.

Standing genetic variance for female resistance to harm from males and its relationship to intralocus sexual conflict.

Interlocus sexual conflict theory predicts that some male adaptations are harmful to their mates. Females are therefore expected to evolve resistance to this harm. Using cytogenetic cloning techniques, we tested for heritable genetic variation among females for resistance to harm from males and determined whether propensity to remate, female body size, and intralocus conflict contributes to this variation. We found low but significant heritability for female resistance, but this variation accounted for more than half of the standing genetic variation for net fitness among females. We found no association between female resistance and female body size or level of intralocus sexual conflict. Reluctance to remate was found to be an important factor contributing to the female resistance phenotype, and we found a positive selection gradient on this trait. However, we observed only a nonsignificant positive correlation between a female's resistance and her net fitness. One factor contributing to the observed nominal level of selection on female resistance was that males cause the greatest amount of harm to females with the highest intrinsic fecundity.

Genetic models of homosexuality: generating testable predictions.

Homosexuality is a common occurrence in humans and other species, yet its genetic and evolutionary basis is poorly understood. Here, we formulate and study a series of simple mathematical models for the purpose of predicting empirical patterns that can be used to determine the form of selection that leads to polymorphism of genes influencing homosexuality. Specifically, we develop theory to make contrasting predictions about the genetic characteristics of genes influencing homosexuality including: (i) chromosomal location, (ii) dominance among segregating alleles and (iii) effect sizes that distinguish between the two major models for their polymorphism: the overdominance and sexual antagonism models. We conclude that the measurement of the genetic characteristics of quantitative trait loci (QTLs) found in genomic screens for genes influencing homosexuality can be highly informative in resolving the form of natural selection maintaining their polymorphism.

Evidence for adaptive male mate choice in the fruit fly Drosophila melanogaster.

Theory predicts that males will benefit when they bias their mating effort towards females of higher reproductive potential, and that this discrimination will increase as males become more resource limited. We conducted a series of experiments to test these predictions in a laboratory population of the fruitfly, Drosophila melanogaster. In this species, courtship and copulation have significant costs to males, and females vary greatly in fecundity, which is positively associated with body size. When given a simultaneous choice between small and large virgin females, males preferentially mated with larger, more fecund, females. Moreover, after males had recently mated they showed a stronger preference for larger females. These results suggest that male D. melanogaster adaptively allocate their mating effort in response to variation in female quality and provide some of the first support for the theoretical prediction that male stringency in mate choice increases as resources become more limiting.