Drivers of systemic male-female allele frequency divergence in humans

Abstract

Allele frequency differences between males and females in genetic studies have been interpreted as suggestive of sex differences in natural selection. However, systemic differences may also arise through sex differences in study participation as well as bioinformatic artifacts. To mitigate these confounding effects, we performed a meta-analysis of sex differences in allele frequencies across three genetic studies. We identify twelve concordant genes with cross-study evidence of sex differences in allele frequency. Using previous literature about the twelve candidates, we propose four hypotheses for how and when sex differences in allele frequencies arise and suggest which hypotheses are plausible for each candidate. For example, beyond candidates that plausibly reflect sex differences in viability, we also find candidate loci potentially underlying fitness differences between X/Y-carrying sperm. Taken together, our results offer a clearer delineation of the factors driving sex differences in allele frequencies, including the timing and mechanisms of natural selection.