ArticlePLoS biology2022
Polygenic signals of sex differences in selection in humans from the UK Biobank.
Article in PLoS biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Reverse genetics of sexual antagonism.Nature ecology & evolution · 2026Article
- Drivers of systemic male-female allele frequency divergence in humans.bioRxiv : the preprint server for biology · 2026Article
- The maintenance of genetic polymorphism underlying sexually antagonistic traits.Evolution letters · 2025Article
- No evidence for sex-differential transcriptomes driving genome-wide sex-differential natural selection.American journal of human genetics · 2025Article
- The battle of the sexes in humans is highly polygenic.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Multivariate genetic architecture reveals testosterone-driven sexual antagonism in contemporary humans.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Dominance reversals: the resolution of genetic conflict and maintenance of genetic variation.Proceedings. Biological sciences · 2024Review
- Unveiling recent and ongoing adaptive selection in human populations.PLoS biology · 2024Article
- Sexual antagonism in sequential hermaphrodites.Proceedings. Biological sciences · 2023Article
- An unbiased test reveals no enrichment of sexually antagonistic polymorphisms on the human X chromosome.Proceedings. Biological sciences · 2022Article
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Authors and funding
3 authors.
Funding
Abstract
Sex differences in the fitness effects of genetic variants can influence the rate of adaptation and the maintenance of genetic variation. For example, "sexually antagonistic" (SA) variants, which are beneficial for one sex and harmful for the other, can both constrain adaptation and increase genetic variability for fitness components such as survival, fertility, and disease susceptibility. However, detecting variants with sex-differential fitness effects is difficult, requiring genome sequences and fitness measurements from large numbers of individuals. Here, we develop new theory for studying sex-differential selection across a complete life cycle and test our models with genotypic and reproductive success data from approximately 250,000 UK Biobank individuals. We uncover polygenic signals of sex-differential selection affecting survival, reproductive success, and overall fitness, with signals of sex-differential reproductive selection reflecting a combination of SA polymorphisms and sexually concordant polymorphisms in which the strength of selection differs between the sexes. Moreover, these signals hold up to rigorous controls that minimise the contributions of potential confounders, including sequence mapping errors, population structure, and ascertainment bias. Functional analyses reveal that sex-differentiated sites are enriched in phenotype-altering genomic regions, including coding regions and loci affecting a range of quantitative traits. Population genetic analyses show that sex-differentiated sites exhibit evolutionary histories dominated by genetic drift and/or transient balancing selection, but not long-term balancing selection, which is consistent with theoretical predictions of effectively weak SA balancing selection in historically small populations. Overall, our results are consistent with polygenic sex-differential-including SA-selection in humans. Evidence for sex-differential selection is particularly strong for variants affecting reproductive success, in which the potential contributions of nonrandom sampling to signals of sex differentiation can be excluded.
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