Abstract
BackgroundThe prevalence of several human morbid phenotypes is sometimes much higher than intuitively expected. This can directly arise from the presence of two sexes, male and female, in one species. Men and women have almost identical genomes but are distinctly dimorphic, with dissimilar disease susceptibilities. Sexually dimorphic traits mainly result from differential expression of genes present in both sexes. Such genes can be subject to different, and even opposing, selection constraints in the two sexes. This can impact human evolution by differential selection on mutations with dissimilar effects on the two sexes.ResultsWe comprehensively mapped human sex-differential genetic architecture across 53 tissues. Analyzing available RNA-sequencing data from 544 adults revealed thousands of genes differentially expressed in the reproductive tracts and tissues common to both sexes. Sex-differential genes are related to various biological systems, and suggest new insights into the pathophysiology of diverse human diseases. We also identified a significant association between sex-specific gene transcription and reduced selection efficiency and accumulation of deleterious mutations, which might affect the prevalence of different traits and diseases. Interestingly, many of the sex-specific genes that also undergo reduced selection efficiency are essential for successful reproduction in men or women. This seeming paradox might partially explain the high incidence of human infertility.ConclusionsThis work provides a comprehensive overview of the sex-differential transcriptome and its importance to human evolution and human physiology in health and in disease.
Highlights
The prevalence of several human morbid phenotypes is sometimes much higher than intuitively expected
We found that three of these X-linked genes are located at pseudo-autosomal region 1 (PAR1), which undergoes relatively frequent recombination between the X and Y chromosomes and is known to escape Xinactivation [33] (Additional file 5: Table S2; Additional file 6: Figure S4)
Analyzing selection on highly and moderately menand women-specific genes, we found a significant association with reduced selection efficiency, as reflected in their dDNS/dS and dStop/dS ratios (Table 1, Fig. 6)
Summary
The prevalence of several human morbid phenotypes is sometimes much higher than intuitively expected This can directly arise from the presence of two sexes, male and female, in one species. Dimorphic traits mainly result from differential expression of genes present in both sexes. Such genes can be subject to different, and even opposing, selection constraints in the two sexes. This can impact human evolution by differential selection on mutations with dissimilar effects on the two sexes. Different selection constraints are expected on these genes in males and females Such cases can lead to reduced purifying
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