Expression profiling by high throughput sequencing
Sex differences are widespread in human health and disease, which are frequently modeled in other mammalian species. However, the extent to which molecular sex differences are conserved across both tissues and species remains unclear. We conducted a 12-tissue, five-species survey of sex differences in gene expression using both publicly available (human) and newly generated (cynomolgus macaque, mouse, rat, and dog) RNA sequencing data. In each of the tissues assessed, we identified between 128 and 805 genes with conserved sex-biased expression. However, most sex bias in gene expression (~77%) – both female and male – has arisen since the last common ancestor of boroeutherian mammals, likely facilitated by reduced selective constraint. Evolutionary gains and losses of regulation by sex-biased transcription factors drove a significant fraction (~27%) of lineage-specific changes in sex bias. Our study suggests caution in the use of other species as models of human sex differences, and that similar selective pressures have driven sex-biased gene expression both within and outside the reproductive tract.
Tissue transcriptomes from 12 tissues and 4 species, 3 males and 3 females per species (before removal of outliers) were sequenced and compared for sex differences