| Method |
P.2 right column top paragraph: "Here, by rigorous analysis of RNA-sequencing (RNA-seq) data from the GTEx [Genotype-Tissue Expression] project [refs 27, 28], [investigators] have comprehensively mapped, for the first time, human adults sex-differential gene expression over 45 tissues common to both sexes. [They] then identified highly and moderately sex-specific genes while considering the complete panel of 53 tissues." |
| Comments |
P.7 left column bottom paragraph: "Selection analyses of sex-specific and moderately sex-specific genes-[Investigators] have previously shown that human testis-exclusive genes are under reduced selection [ref 24]. All 1100 of 1295 men testis-overexpressed genes identified here that are covered in the 1000 Genomes Project were also found to have significantly higher dDNS/dS and dStop/dS ratios (Table 1). This gene set includes 77 out of 95 of the genes [they] previously identified as testis exclusive [ref 24]. The other 18 out of 95 genes that [they] previously found to be specifically expressed in testis tissues might not be identified here because these tissues are not present in the GTEx samples. The non-testis men-specific and moderately women-specific genes also had significantly higher dDNS/dS ratios (Table 1, Fig. 6). The significantly higher dDNS/dS ratio of these men-specific genes did not depend on the presence of the 55 keratin genes (Table 1). women-specific genes too had a significantly higher dDNS/dS ratio (Table 1, Fig. 6). Moderately women-specific genes had a higher, yet not significant, dDNS/dS ratio (Table 1). However, when comparing the moderately women-specific genes to non sex-specific genes, [they] found the dDNS ratios to be significantly higher for the moderately women-specific genes (1.66 fold change, Fisher’s exact test p-value <1 × 10^−4) but the dS ratios showed no significant change (1.08 fold change, Fisher’s exact test p-value = 1.5 × 10^−1). Thus, moderately women-specific genes have significantly reduced selection relative to non sex-specific genes. The same analysis for dStop/dS of men- and women-specific genes also found significantly reduced selection (Table 1). A significant reduction in purifying selection on sex-specific genes was hence found by independent analyses of selection on DNS and stop-gain mutations on diverse sets of sex-specific genes from both women and men, including sets from non-reproduction-related tissues. It is also notable that although reduced selection was observed for both men- and women-specific genes, it was higher in men-specific genes compared to women-specific genes (Fig. 6, Table 1)." dDNS=deleterious non-synonymous, dS=deleterious synonymous, dSTOP=deleterious stop-gain, MAF=minor allele frequency |