Conservation, acquisition, and functional impact of sex-biased gene expression in mammalian tissues

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

性别差异广泛存在于人类健康与疾病领域，此类差异常以其他哺乳动物为模型开展相关研究。然而，分子层面的性别差异在不同组织与物种间的保守程度仍不明确。
本研究针对12种组织、5个物种开展基因表达性别差异的系统性分析，整合使用了公开获取的人类样本数据，以及新生成的食蟹猴、小鼠、大鼠与犬的RNA测序（RNA sequencing）数据。
在所评估的所有组织中，我们共鉴定出128至805个存在保守性性别偏向性表达的基因。
然而，约77%的基因表达性别偏向现象（涵盖雌性偏向与雄性偏向）均起源于真兽类哺乳动物的最近共同祖先之后，这一演化过程可能因选择约束减弱而得到促进。
由性别偏向性转录因子介导的调控进化增益与丢失，解释了约27%的谱系特异性性别偏向性表达变化。
本研究提示，在以其他物种作为人类性别差异研究模型时需保持谨慎；同时，类似的选择压力同时驱动了生殖道内外的性别偏向性基因表达。
本研究对4个物种的12种组织进行了转录组测序，每个物种包含3只雄性与3只雌性个体（剔除异常值前），并针对其中的性别差异开展了比较分析。