The battle of the sexes in humans is highly polygenic

• 成果类型: Article
• 署名作者: Cole, Jared M.; Scott, Carly B.; Johnson, Mackenzie M.; Golightly, Peter R.; Carlson, Jedidiah; Ming, Matthew J.; Harpak, Arbel; Kirkpatrick, Mark
• 署名单位: University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; University of North Carolina; University of North Carolina Chapel Hill; Fred Hutchinson Cancer Center
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9984
• DOI: 10.1073/pnas.2412315121
• 发表日期: 2024-09-16
• 关键词: sexual conflict; Linkage Disequilibrium; selection; fitness; genome; polymorphisms; signature; EVOLUTION; blocks; models

摘要

Sex-differential selection (SDS), which occurs when the fitness effects of alleles differ between males and females, can have profound impacts on the maintenance of genetic variation, disease risk, and other key aspects of natural populations. Because the sexes mix their autosomal genomes each generation, quantifying SDS is not possible using conventional population genetic approaches. Here, we introduce a method that exploits subtle sex differences in haplotype frequencies resulting from SDS acting in the current generation. Using data from 300K individuals in the UK Biobank, we estimate the strength of SDS throughout the genome. While only a handful of loci under SDS are individually significant, we uncover highly polygenic signals of genome-wide SDS for both viability and fecundity. Selection coefficients of s = 10(-3) may be typical. Despite its ubiquity, SDS may impose a mortality load of less than 1%. An interesting life-history tradeoff emerges: Alleles that increase viability more strongly in females than males tend to increase fecundity more strongly in males than in females. Finally, we find marginal evidence of SDS on fecundity acting on alleles affecting arm fat-free mass. Taken together, our findings connect the long-standing evidence of SDS acting on human phenotypes with its impact on the genome.