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

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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.

Original languageEnglish
Pages (from-to)20212314
Number of pages9
JournalProceedings of the Royal Society B: Biological Sciences
Volume289
Issue number1967
DOIs
Publication statusPublished - 26 Jan 2022

Keywords

  • empirical population genomics
  • FST
  • humans
  • sex chromosomes
  • sexually antagonistic selection
  • theoretical models

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