The battle of the sexes in humans is highly polygenic.

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 [Formula: see text] 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.

Amplification is the primary mode of gene-by-sex interaction in complex human traits.

Sex differences in complex traits are suspected to be in part due to widespread gene-by-sex interactions (GxSex), but empirical evidence has been elusive. Here, we infer the mixture of ways in which polygenic effects on physiological traits covary between males and females. We find that GxSex is pervasive but acts primarily through systematic sex differences in the magnitude of many genetic effects ("amplification") rather than in the identity of causal variants. Amplification patterns account for sex differences in trait variance. In some cases, testosterone may mediate amplification. Finally, we develop a population-genetic test linking GxSex to contemporary natural selection and find evidence of sexually antagonistic selection on variants affecting testosterone levels. Our results suggest that amplification of polygenic effects is a common mode of GxSex that may contribute to sex differences and fuel their evolution.

Selection and isolation define a heterogeneous divergence landscape between hybridizing Heliconius butterflies.

Hybridizing species provide a powerful system to identify the processes that shape genomic variation and maintain species boundaries. However, complex histories of isolation, gene flow, and selection often generate heterogeneous genomic landscapes of divergence that complicate reconstruction of the speciation history. Here, we explore patterns of divergence to reconstruct recent speciation in the erato clade of Heliconius butterflies. We focus on the genomic landscape of divergence across three contact zones of the species H. erato and H. himera. We show that these hybridizing species have an intermediate level of divergence in the erato clade, which fits with their incomplete levels of reproductive isolation. Using demographic modeling and the relationship between admixture and divergence with recombination rate variation, we reconstruct histories of gene flow, selection, and demographic change that explain the observed patterns of genomic divergence. We find that periods of isolation and selection within populations, followed by secondary contact with asymmetrical gene flow are key factors in shaping the heterogeneous genomic landscapes. Collectively, these results highlight the effectiveness of demographic modeling and recombination rate estimates to disentangling the distinct contributions of gene flow and selection to patterns of genomic divergence.