PURGING THE GENOME WITH SEXUAL SELECTION: REDUCING MUTATION LOAD THROUGH SELECTION ON MALES

Healthy males are likely to have higher mating success than unhealthy males because of differential expression of condition‐dependent traits such as mate searching intensity, fighting ability, display vigor, and some types of exaggerated morphological characters. We therefore expect that most new mutations that are deleterious for overall fitness may also be deleterious for male mating success. From this perspective, sexual selection is not limited to influencing those genes directly involved in exaggerated morphological traits but rather affects most, if not all, genes in the genome. If true, sexual selection can be an important force acting to reduce the frequency of deleterious mutations and, as a result, mutation load. We review the literature and find various forms of indirect evidence that sexual selection helps to eliminate deleterious mutations. However, direct evidence is scant, and there are almost no data available to address a key issue: is selection in males stronger than selection in females? In addition, the total effect of sexual selection on mutation load is complicated by possible increases in mutation rate that may be attributable to sexual selection. Finally, sexual selection affects population fitness not only through mutation load but also through sexual conflict, making it difficult to empirically measure how sexual selection affects load. Several lines of enquiry are suggested to better fill large gaps in our understanding of sexual selection and its effect on genetic load.     

Heterozygosity-fitness correlations among wild populations of European tree frog (Hyla arborea) detect fixation load

Quantifying the impacts of inbreeding and genetic drift on fitness traits in fragmented populations is becoming a major goal in conservation biology. Such impacts occur at different levels and involve different sets of loci. Genetic drift randomly fixes slightly deleterious alleles leading to different fixation load among populations. By contrast, inbreeding depression arises from highly deleterious alleles in segregation within a population and creates variation among individuals. A popular approach is to measure correlations between molecular variation and phenotypic performances. This approach has been mainly used at the individual level to detect inbreeding depression within populations and sometimes at the population level but without consideration about the genetic processes measured. For the first time, we used in this study a molecular approach considering both the interpopulation and intrapopulation level to discriminate the relative importance of inbreeding depression vs. fixation load in isolated and non-fragmented populations of European tree frog (Hyla arborea), complemented with interpopulational crosses. We demonstrated that the positive correlations observed between genetic heterozygosity and larval performances on merged data were mainly caused by co-variations in genetic diversity and fixation load among populations rather than by inbreeding depression and segregating deleterious alleles within populations. Such a method is highly relevant in a conservation perspective because, depending on how populations lose fitness (inbreeding vs. fixation load), specific management actions may be designed to improve the persistence of populations.     

Factors affecting the genetic load in Drosophila: synergistic epistasis and correlations among fitness components

Two factors that can affect genetic load, synergistic epistasis and sexual selection, were investigated in Drosophila melanogaster. A set of five chromosomal regions containing visible recessive mutations were put together in all combinations to create a full set of 32 homozygous lines fixed for different numbers of known mutations. Two measures of fitness were made for each line: productivity (a combined measure of fecundity and egg-to-adult survivorship) and competitive male mating success. Productivity, but not male mating success, showed a pattern of strong average synergistic epistasis, such that the log fitness declined nonlinearly with increasing numbers of mutations. Synergistic epistasis is known to reduce the mutation load. Both fitness components show some positive and some negative interactions between specific sets of mutations. Furthermore, alleles with deleterious effects on productivity tend to also diminish male mating success. Given that male mating success can affect relative fitness without changing the mean productivity of a population, these additional effects would lead to lower frequencies and lower fixation rates of deleterious alleles without higher costs to the mean fitness of the population.     

MULTI‐LEVEL SEXUAL SELECTION: INDIVIDUAL AND FAMILY‐LEVEL SELECTION FOR MATING SUCCESS IN A HISTORICAL HUMAN POPULATION

Precopulatory sexual selection is the association between fitness and traits associated with mate acquisition. Although sexual selection is generally recognized to be a powerful evolutionary force, most investigations are limited to characters belonging to individuals. A broader multilevel perspective acknowledges that individual fitness can be affected by aspects of mating success that are characters of groups, such as families. Parental mating success in polygynous or polyandrous human societies may exemplify traits under group‐level sexual selection. Using fitness measures that account for age‐structure, I measure multilevel selection for mate number over 55 years in a human population with declining rates of polygyny. Sexual selection had three components: individual‐level selection for ever‐mating (whether an individual mated) and individual‐ and family‐level selection for polyandry and polygyny. Family‐ and individual‐level selection for polygyny was equally strong, three times stronger than family‐level selection for polyandry and more than an order of magnitude stronger than individual‐level selection for polyandry. However, individual‐level selection for polyandry and polygyny was more effective at explaining relative fitness variance than family‐level selection. Selection for ever‐mating was the most important source of sexual selection for fitness; variation for ever‐mating explained 23% of relative fitness variance.     

Sexual selection and its effect on the fixation of an asexual clone

Sexual selection is a powerful and ubiquitous force in sexual populations. It has recently been argued that sexual selection can eliminate the twofold cost of sex even with low genomic mutation rates. By means of differential male mating success, deleterious mutations in males become more deleterious than in females, and it has been shown that sexual selection can drastically reduce the mutational load in a sexual population, with or without any form of epistasis. However, any mechanism that claims to maintain sexual reproduction must be able to prevent the fixation of an asexual mutant clone with a twofold fitness advantage. Here, I show that despite very strong sexual selection, the fixation of an asexual mutant cannot be prevented under reasonable genomic mutation rates. Sexual selection can have a strong effect on the average mutational load in a sexual population, but as it cannot prevent the fixation of an asexual mutant, it is unlikely to play a key role on the maintenance of sexual reproduction.     

Mating patterns influence vulnerability to the extinction vortex

Earth's biodiversity is undergoing mass extinction due to anthropogenic compounding of environmental, demographic and genetic stresses. These different stresses can trap populations within a reinforcing feedback loop known as the extinction vortex, in which synergistic pressures build upon one another through time, driving down population viability. Sexual selection, the widespread evolutionary force arising from competition, choice and reproductive variance within animal mating patterns could have vital consequences for population viability and the extinction vortex: (a) if sexual selection reinforces natural selection to fix ‘good genes’ and purge ‘bad genes’, then mating patterns encouraging competition and choice may help protect populations from extinction; (b) by contrast, if mating patterns create load through evolutionary or ecological conflict, then population viability could be further reduced by sexual selection. We test between these opposing theories using replicate populations of the model insect Tribolium castaneum exposed to over 10 years of experimental evolution under monogamous versus polyandrous mating patterns. After a 95‐generation history of divergence in sexual selection, we compared fitness and extinction of monogamous versus polyandrous populations through an experimental extinction vortex comprising 15 generations of cycling environmental and genetic stresses. Results showed that lineages from monogamous evolutionary backgrounds, with limited opportunities for sexual selection, showed rapid declines in fitness and complete extinction through the vortex. By contrast, fitness of populations from the history of polyandry, with stronger opportunities for sexual selection, declined slowly, with 60% of populations surviving by the study end. The three vortex stresses of (a) nutritional deprivation, (b) thermal stress and (c) genetic bottlenecking had similar impacts on fitness declines and extinction risk, with an overall sigmoid decline in survival through time. We therefore reveal sexual selection as an important force behind lineages facing extinction threats, identifying the relevance of natural mating patterns for conservation management.     

Reducing mutation load through sexual selection on males

Mutation load is a key parameter in evolutionary theories, but relatively little empirical information exists on the mutation load of populations, or the elimination of this load through selection. We manipulated the opportunity for sexual selection within a mutation accumulation divergence experiment to determine how sexual selection on males affected the accumulation of mutations contributing to sexual and nonsexual fitness. Sexual selection prevented the accumulation of mutations affecting male mating success, the target trait, as well as reducing mutation load on productivity, a nonsexual fitness component. Mutational correlations between mating success and productivity (estimated in the absence of sexual selection) were positive. Sexual selection significantly reduced these fitness component correlations. Male mating success significantly diverged between sexual selection treatments, consistent with the fixation of genetic differences. However, the rank of the treatments was not consistent across assays, indicating that the mutational effects on mating success were conditional on biotic and abiotic context. Our experiment suggests that greater insight into the genetic targets of natural and sexual selection can be gained by focusing on mutational rather than standing genetic variation, and on the behavior of trait variances rather than means.     

Dynamics of inbreeding depression due to deleterious mutations in small populations: mutation parameters and inbreeding rate

A multilocus stochastic model is developed to simulate the dynamics of mutational load in small populations of various sizes. Old mutations sampled from a large ancestral population at mutation-selection balance and new mutations arising each generation are considered jointly, using biologically plausible lethal and deleterious mutation parameters. The results show that inbreeding depression and the number of lethal equivalents due to partially recessive mutations can be partly purged from the population by inbreeding, and that this purging mainly involves lethals or detrimentals of large effect. However, fitness decreases continuously with inbreeding, due to increased fixation and homozygosity of mildly deleterious mutants, resulting in extinctions of very small populations with low reproductive rates. No optimum inbreeding rate or population size exists for purging with respect to fitness (viability) changes, but there is an optimum inbreeding rate at a given final level of inbreeding for reducing inbreeding depression or the number of lethal equivalents. The interaction between selection against partially recessive mutations and genetic drift in small populations also influences the rate of decay of neutral variation. Weak selection against mutants relative to genetic drift results in apparent overdominance and thus an increase in effective size (Ne) at neutral loci, and strong selection relative to drift leads to a decrease in Ne due to the increased variance in family size. The simulation results and their implications are discussed in the context of biological conservation and tests for purging.     

Drift load in populations of small size and low density

According to theory, drift load in randomly mating populations is determined by past population size, because enhanced genetic drift in small populations causes accumulation and fixation of recessive deleterious mutations of small effect. In contrast, segregating load due to mutations of low frequency should decline in smaller populations, at least when mutations are highly recessive and strongly deleterious. Strong local selection generally reduces both types of load. We tested these predictions in 13 isolated, outcrossing populations of Arabidopsis lyrata that varied in population size and plant density. Long-term size was estimated by expected heterozygosity at 20 microsatellite loci. Segregating load was assessed by comparing performance of offspring from selfings versus within-population crosses. Drift load was the heterosis effect created by interpopulation outbreeding. Results showed that segregating load was unrelated to long-term size. However, drift load was significantly higher in populations of small effective size and low density. Drift load was mostly expressed late in development, but started as early as germination and accumulated thereafter. The study largely confirms predictions of theory and illustrates that mutation accumulation can be a threat to natural populations.     

A general population genetic framework for antagonistic selection that accounts for demography and recurrent mutation

Antagonistic selection--where alleles at a locus have opposing effects on male and female fitness ("sexual antagonism") or between components of fitness ("antagonistic pleiotropy")--might play an important role in maintaining population genetic variation and in driving phylogenetic and genomic patterns of sexual dimorphism and life-history evolution. While prior theory has thoroughly characterized the conditions necessary for antagonistic balancing selection to operate, we currently know little about the evolutionary interactions between antagonistic selection, recurrent mutation, and genetic drift, which should collectively shape empirical patterns of genetic variation. To fill this void, we developed and analyzed a series of population genetic models that simultaneously incorporate these processes. Our models identify two general properties of antagonistically selected loci. First, antagonistic selection inflates heterozygosity and fitness variance across a broad parameter range--a result that applies to alleles maintained by balancing selection and by recurrent mutation. Second, effective population size and genetic drift profoundly affect the statistical frequency distributions of antagonistically selected alleles. The "efficacy" of antagonistic selection (i.e., its tendency to dominate over genetic drift) is extremely weak relative to classical models, such as directional selection and overdominance. Alleles meeting traditional criteria for strong selection (N(e)s > 1, where N(e) is the effective population size, and s is a selection coefficient for a given sex or fitness component) may nevertheless evolve as if neutral. The effects of mutation and demography may generate population differences in overall levels of antagonistic fitness variation, as well as molecular population genetic signatures of balancing selection.     

Fixation of new alleles and the extinction of small populations: drift load, beneficial alleles, and sexual selection

With a small effective population size, random genetic drift is more important than selection in determining the fate of new alleles. Small populations therefore accumulate deleterious mutations. Left unchecked, the effect of these fixed alleles is to reduce the reproductive capacity of a species, eventually to the point of extinction. New beneficial mutations, if fixed by selection, can restore some of this lost fitness. This paper derives the overall change in fitness due to fixation of new deleterious and beneficial alleles, as a function of the distribution of effects of new mutations and the effective population size. There is a critical effective size below which a population will on average decline in fitness, but above which beneficial mutations allow the population to persist. With reasonable estimates of the relevant parameters, this critical effective size is likely to be a few hundred. Furthermore, sexual selection can act to reduce the fixation probability of deleterious new mutations and increase the probability of fixing new beneficial mutations. Sexual selection can therefore reduce the risk of extinction of small populations.     

Genetic load in sexual and asexual diploids: segregation, dominance and genetic drift

In diploid organisms, sexual reproduction rearranges allelic combinations between loci (recombination) as well as within loci (segregation). Several studies have analyzed the effect of segregation on the genetic load due to recurrent deleterious mutations, but considered infinite populations, thus neglecting the effects of genetic drift. Here, we use single-locus models to explore the combined effects of segregation, selection, and drift. We find that, for partly recessive deleterious alleles, segregation affects both the deterministic component of the change in allele frequencies and the stochastic component due to drift. As a result, we find that the mutation load may be far greater in asexuals than in sexuals in finite and/or subdivided populations. In finite populations, this effect arises primarily because, in the absence of segregation, heterozygotes may reach high frequencies due to drift, while homozygotes are still efficiently selected against; this is not possible with segregation, as matings between heterozygotes constantly produce new homozygotes. If deleterious alleles are partly, but not fully recessive, this causes an excess load in asexuals at intermediate population sizes. In subdivided populations without extinction, drift mostly occurs locally, which reduces the efficiency of selection in both sexuals and asexuals, but does not lead to global fixation. Yet, local drift is stronger in asexuals than in sexuals, leading to a higher mutation load in asexuals. In metapopulations with turnover, global drift becomes again important, leading to similar results as in finite, unstructured populations. Overall, the mutation load that arises through the absence of segregation in asexuals may greatly exceed previous predictions that ignored genetic drift.     

Adaptive divergence despite strong genetic drift: genomic analysis of the evolutionary mechanisms causing genetic differentiation in the island fox (Urocyon littoralis)

The evolutionary mechanisms generating the tremendous biodiversity of islands have long fascinated evolutionary biologists. Genetic drift and divergent selection are predicted to be strong on islands and both could drive population divergence and speciation. Alternatively, strong genetic drift may preclude adaptation. We conducted a genomic analysis to test the roles of genetic drift and divergent selection in causing genetic differentiation among populations of the island fox (Urocyon littoralis). This species consists of six subspecies, each of which occupies a different California Channel Island. Analysis of 5293 SNP loci generated using Restriction‐site Associated DNA (RAD) sequencing found support for genetic drift as the dominant evolutionary mechanism driving population divergence among island fox populations. In particular, populations had exceptionally low genetic variation, small N_e (range = 2.1–89.7; median = 19.4), and significant genetic signatures of bottlenecks. Moreover, islands with the lowest genetic variation (and, by inference, the strongest historical genetic drift) were most genetically differentiated from mainland grey foxes, and vice versa, indicating genetic drift drives genome‐wide divergence. Nonetheless, outlier tests identified 3.6–6.6% of loci as high F_ST outliers, suggesting that despite strong genetic drift, divergent selection contributes to population divergence. Patterns of similarity among populations based on high F_ST outliers mirrored patterns based on morphology, providing additional evidence that outliers reflect adaptive divergence. Extremely low genetic variation and small N_e in some island fox populations, particularly on San Nicolas Island, suggest that they may be vulnerable to fixation of deleterious alleles, decreased fitness and reduced adaptive potential.     

Effects of population size and isolation on heterosis, mean fitness, and inbreeding depression in a perennial plant

? In small isolated populations, genetic drift is expected to increase chance fixation of partly recessive, mildly deleterious mutations, reducing mean fitness and inbreeding depression within populations and increasing heterosis in outcrosses between populations. ? We estimated relative effective sizes and migration among populations and compared mean fitness, heterosis, and inbreeding depression for eight large and eight small populations of a perennial plant on the basis of fitness of progeny produced by hand pollinations within and between populations. ? Migration was limited, and, consistent with expectations for drift, mean fitness was 68% lower in small populations; heterosis was significantly greater for small (mean?=?70%, SE?=?14) than for large populations (mean?=?7%, SE?=?27); and inbreeding depression was lower, although not significantly so, in small (mean?=?-0.29%, SE?=?28) than in large (mean?=?0.28%, SE?=?23) populations. ? Genetic drift promotes fixation of deleterious mutations in small populations, which could threaten their persistence. Limited migration will exacerbate drift, but data on migration and effective population sizes in natural populations are scarce. Theory incorporating realistic variation in population size and patterns of migration could better predict genetic threats to small population persistence.     

The effect of parasites on sex differences in selection

The life history strategies of males and females are often divergent, creating the potential for sex differences in selection. Deleterious mutations may be subject to stronger selection in males, owing to sexual selection, which can improve the mean fitness of females and reduce mutation load in sexual populations. However, sex differences in selection might also maintain sexually antagonistic genetic variation, creating a sexual conflict load. The overall impact of separate sexes on fitness is unclear, but the net effect is likely to be positive when there is a large sex difference in selection against deleterious mutations. Parasites can also have sex-specific effects on fitness, and there is evidence that parasites can intensify the fitness consequences of deleterious mutations. Using lines that accumulated mutations for over 60 generations, we studied the effect of the pathogenic bacterium Pseudomonas aeruginosa on sex differences in selection in the fruit fly Drosophila melanogaster. Pseudomonas infection increased the sex difference in selection, but may also have weakened the intersexual correlation for fitness. Our results suggest that parasites may increase the benefits of sexual selection.     

Inbreeding reveals stronger net selection on Drosophila melanogaster males: implications for mutation load and the fitness of sexual females

Stronger selection on males has the potential to lower the deleterious mutation load of females, reducing the cost of sex. However, few studies have directly quantified the strength of selection for both sexes. As the magnitude of inbreeding depression (ID) is related to the strength of selection, we measured the cost of inbreeding for both males and females in a laboratory population of Drosophila melanogaster. Using a novel technique for inbreeding, we found significant ID for both juvenile viability and adult fitness in both sexes. The genetic variation responsible for this depression in fitness appeared to be recessive for adult fitness (h=0.11) and partially additive for juvenile viability (h=0.29). ID was identical across the sexes in terms of juvenile viability but was significantly more deleterious for males than females as adults, even though female X-chromosome homogamety should predispose them to a higher inbreeding load. We estimated the strength of selection on adult males to be 1.24 greater than on adult females, and this appears to be a consequence of selection arising from competition for mates. Combined with the generally positive intersexual genetic correlation for inbred lines, our results suggest that the mutation load of sexual females could be meaningfully reduced by stronger selection acting on males.     

Geographical variation in the mating system of the dusky pipefish (Syngnathus floridae)

Differences among populations in the intensity of sexual selection resulting from distinct genetic mating systems can lead to divergent morphological evolution and speciation. However, little is known about how genetic mating systems vary between populations and what factors may contribute to this variation. In this study, we compare the genetic mating systems of two geographically distinct populations of the dusky pipefish (Syngnathus floridae), a species characterized by polygynandry and male pregnancy, from the Atlantic Coast of Virginia and the Gulf Coast of Florida. Our results revealed significant interpopulation variation in mating and reproductive success. Estimates of the opportunity for selection (I), the opportunity for sexual selection (I(s)) and the Bateman gradient (beta(ss)) were higher among males in the Florida population than in the Virginia population, suggesting that sexual selection on males is stronger in the Florida population. The Virginia population is larger and denser than the Florida population, suggesting that population demographics may be one of many causal factors shaping interpopulational mating patterns. This study also provides evidence that the adult sex ratio, operational sex ratio, population density and genetic mating system of S. floridae may be temporally stable over timescales of a month in the Florida population. Overall, our results show that this species is a good model for the study of mating system variation in nature and that Bateman's principles may be a useful technique for the quantitative comparison of mating systems between populations.     

Sex‐specific selection under environmental stress in seed beetles

Sexual selection can increase rates of adaptation by imposing strong selection in males, thereby allowing efficient purging of the mutation load on population fitness at a low demographic cost. Indeed, sexual selection tends to be male‐biased throughout the animal kingdom, but little empirical work has explored the ecological sensitivity of this sex difference. In this study, we generated theoretical predictions of sex‐specific strengths of selection, environmental sensitivities and genotype‐by‐environment interactions and tested them in seed beetles by manipulating either larval host plant or rearing temperature. Using fourteen isofemale lines, we measured sex‐specific reductions in fitness components, genotype‐by‐environment interactions and the strength of selection (variance in fitness) in the juvenile and adult stage. As predicted, variance in fitness increased with stress, was consistently greater in males than females for adult reproductive success (implying strong sexual selection), but was similar in the sexes in terms of juvenile survival across all levels of stress. Although genetic variance in fitness increased in magnitude under severe stress, heritability decreased and particularly so in males. Moreover, genotype‐by‐environment interactions for fitness were common but specific to the type of stress, sex and life stage, suggesting that new environments may change the relative alignment and strength of selection in males and females. Our study thus exemplifies how environmental stress can influence the relative forces of natural and sexual selection, as well as concomitant changes in genetic variance in fitness, which are predicted to have consequences for rates of adaptation in sexual populations.     

MALE‐BIASED FITNESS EFFECTS OF SPONTANEOUS MUTATIONS IN DROSOPHILA MELANOGASTER

In populations with males and females, sexual selection may often represent a major component of overall selection. Sexual selection could act to eliminate deleterious alleles in concert with other forms of selection, thereby improving the fitness of sexual populations. Alternatively, the divergent reproductive strategies of the sexes could promote the maintenance of sexually antagonistic variation, causing sexual populations to be less fit. The net impact of sexual selection on fitness is not well understood, due in part to limited data on the sex‐specific effects of spontaneous mutations on total fitness. Using a set of mutation accumulation lines of Drosophila melanogaster, we found that mutations were deleterious in both sexes and had larger effects on fitness in males than in females. This pattern is expected to reduce the mutation load of sexual females and promote the maintenance of sexual reproduction.