Genetic variants experiencing sexually antagonistic selection in humans

Abstract

The two sexes are so different that a genetic variant may function differentially in males and females. Because the evolutionary interests of the sexes never exactly coincide and the two sexes share most of their genetic materials (all except the Y chromosome in mammals), conflicting natural selection can arise. Shared variants or traits undergo differential natural selection between the sexes, resulting in selection for a shared trait in one sex displacing the other sex from its optimum. The phenomenon of sexually antagonistic (SA) selection has been demonstrated in a wide range of taxa, including animals, insects and dioecious plans. However, it has not been widely studied in humans, and clear evidence is still rare. Furthermore, very little is known for the genetics underlying SA selection.

In this thesis, SA selection in humans is studied at the viability level. Males and females are expected to share the same genotype distribution at autosomal loci. Thus, significant differences in genotype distribution at single-nucleotide polymorphisms (SNPs) between the sexes is an indicator of SA selection at the viability level. Genome-wide SNP data were the main materials used in the study. SNP data was obtained from white European control cohort of the Wellcome Trust Case Control Consortium, which is a representative population sample. After quality control, ~4,800 individuals were included in the analysis with approximately equal numbers of males and females, and for each individual there were ~1.2 million genotyped autosomal SNPs available. Comparison of genotype distribution between the sexes at these SNPs provides evidence for ongoing conflicting natural selection between the sexes in humans. This is confirmed by examination of SNPs from genes associated with early onset disease and from genes related to sex hormone function. The former indicates that it is sex-specific differences of viability and/or mortality that lead to differences in genotype distributions between the sexes. The latter indicates that differences in sex hormones contribute to sex-differential viability or mortality. Candidate genes from regions with signatures of SA selection are presented. These candidate genes are important materials for studying the genetic mechanisms underlying SA selection. They may be associated with sex-differential prenatal viability and thus with spontaneous abortion. They may also be associated with sex differences in infant health and disease occurrence later in life. -- provided by Candidate.