The landscape of sex-differential transcriptome and its consequent selection in human adults.
The landscape of sex-differential transcriptome and its consequent selection in human adults.
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DOI：
10.1186/s12915-017-0352-z
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发表时间：
2017-02-07
期刊：
影响因子：
5.4
通讯作者：
Pietrokovski S
中科院分区：
文献类型：
--
作者：
Gershoni M;Pietrokovski S
几种人类病态表型的流行率有时远高于直觉预期。这可能直接源于一个物种中存在两种性别，雄性和雌性。男性和女性有几乎相同的基因组，但明显的二态性，具有不同的疾病易感性。性二型性状主要是由于两性基因表达的差异造成的。此类基因在两性中可能会受到不同甚至相反的选择限制。这可能会影响人类进化的差异选择突变不同的影响两性。我们在53种组织中全面绘制了人类性别差异遗传结构。对544名成年人的RNA测序数据进行分析后发现，在两性共同的生殖道和组织中有数千个差异表达的基因。性别差异基因与多种生物系统相关，并为人类多种疾病的病理生理学提供了新的见解。我们还确定了性别特异性基因转录与选择效率降低和有害突变积累之间的显着关联，这可能会影响不同性状和疾病的患病率。有趣的是，许多性别特异性基因也会降低选择效率，这些基因对于男性或女性的成功繁殖至关重要。这种看似矛盾的现象或许可以部分解释人类不育症的高发率。这项工作提供了一个全面的概述性别差异转录组及其重要性，人类进化和人类生理健康和疾病。本文的在线版本（doi：10.1186/s12915-017-0352-z）包含补充材料，可供授权用户使用。
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. 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. We 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. This work provides a comprehensive overview of the sex-differential transcriptome and its importance to human evolution and human physiology in health and in disease. The online version of this article (doi:10.1186/s12915-017-0352-z) contains supplementary material, which is available to authorized users.