Abstract
Mutations with beneficial effects in one sex can have deleterious effects in the other. Such ‘sexually antagonistic’ (SA) variants contribute to variation in life-history traits and overall fitness, yet their genomic distribution is poorly resolved. Theory predicts that SA variants could be enriched on the X chromosome or autosomes, yet current empirical tests face two formidable challenges: (i) identifying SA selection in genomic data is difficult; and (ii) metrics of SA variation show persistent biases towards the X, even when SA variants are randomly distributed across the genome. Here, we present an unbiased test of the theory that SA variants are enriched on the X. We first develop models for reproductive FST—a metric for quantifying sex-differential (including SA) effects of genetic variants on lifetime reproductive success—that control for X-linked biases. Comparing data from approximately 250 000 UK Biobank individuals to our models, we find FST elevations consistent with both X-linked and autosomal SA polymorphisms affecting reproductive success in humans. However, the extent of FST elevations does not differ from a model in which SA polymorphisms are randomly distributed across the genome. We argue that the polygenic nature of SA variation, along with sex asymmetries in SA effects, might render X-linked enrichment of SA polymorphisms unlikely.
Highlights
Adaptation requires genetic variation for fitness, yet we know surprisingly little about its genetic basis [1,2]
Is fitness variation mostly attributable to rare variants maintained by recurrent mutation, or to common variants maintained by various forms of balancing selection? To what extent are the frequencies of fitness-affecting variants influenced by genetic drift, departures from equilibrium or gene flow from neighbouring populations? To what extent do loci with large versus small fitness effects contribute to genome-wide fitness variation? how are these genetic variants distributed across the genome? These are some of the most pressing questions in evolutionary biology, yet they are the most challenging to answer [3]
Evidence for enrichment of Sexually antagonistic (SA) variants on the X chromosome might imply that SA polymorphisms evolve under balancing selection, with male-beneficial variants typically recessive and female-beneficial variants typically dominant [18,19]
Summary
Adaptation requires genetic variation for fitness, yet we know surprisingly little about its genetic basis [1,2]. The second is that X-linkage inflates empirical signals of SA polymorphism, which can lead to biases in detection and erroneous inferences of elevated SA polymorphism on the X [23] These biases arise, on the one hand, from less constrained conditions for allele frequency divergence between the sexes at X-linked compared to autosomal loci [23,29,30], and, on the other hand, from the inherently stronger effects of X-linked compared to autosomal polymorphisms on male fitness variances and cross-sex fitness covariances [23,28,36,37,38]. By comparing polygenic signals of SA polymorphism in the UK Biobank to this theoretical baseline, we control for both the elevated sampling variance and stronger effects of X-linked polymorphisms on the reproductive FST metric [23,28,36,37,38], allowing us to assess whether SA polymorphisms are disproportionately autosomal or X-linked
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