An unbiased test reveals no enrichment of sexually antagonistic polymorphisms on the human X chromosome

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 F-ST-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 F-ST elevations consistent with both X-linked and autosomal SA polymorphisms affecting reproductive success in humans. However, the extent of F-ST 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.

Automated summary

Mutations with beneficial effects in one sex can have deleterious effects in the other. These sexually antagonistic variants contribute to variations in life-history traits and overall fitness. However, their genomic distribution is still unclear. It is predicted that sexually antagonistic variants could be more common on the X chromosome or autosomes, but current empirical tests face challenges in identifying these variants in genomic data and show biases towards the X chromosome when measuring sexually antagonistic variation.