Polygenic signals of sex differences in selection in humans from the UK Biobank.
Journal
PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
30
09
2021
accepted:
27
07
2022
revised:
16
09
2022
pubmed:
7
9
2022
medline:
21
9
2022
entrez:
6
9
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36067235
doi: 10.1371/journal.pbio.3001768
pii: PBIOLOGY-D-21-02588
pmc: PMC9481184
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3001768Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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