Mammalian pluripotent stem cells (PSCs) have distinct molecular and biological characteristics among species, but to date we lack a comprehensive understanding of regulatory network evolution in mammals. Here, we carried out a comparative genetic analysis of 134 genes constituting the pluripotency gene regulatory network across 48 mammalian species covering all the major taxonomic groups. We report that mammalian genes in the pluripotency regulatory network show a remarkably high degree of evolutionary stasis, suggesting the conservation of fundamental biological process of mammalian PSCs across species. Nevertheless, despite the overall conservation of the regulatory network, we discovered rapid evolution of the downstream targets of the core regulatory elements and specific amino acid residues that have undergone positive selection. Our data indicate development of lineage-specific pluripotency regulating networks that may explain observed variations in some characteristics of mammalian PSCs. We further revealed that positively selected genes could be associated with species’ unique adaptive characteristics that were not dedicated to regulation of PSCs. These results provide important insight into the evolution of the pluripotency gene regulatory network underlying variations in characteristics of mammalian PSCs.

中文翻译：

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哺乳动物多能性基因调控网络进化的遗传特征。


哺乳动物多能干细胞（PSC）在物种之间具有独特的分子和生物学特征，但迄今为止我们缺乏对哺乳动物调控网络进化的全面了解。在这里，我们对涵盖所有主要分类群的 48 个哺乳动物物种的构成多能性基因调控网络的 134 个基因进行了比较遗传分析。我们报告说，多能性调控网络中的哺乳动物基因表现出非常高程度的进化停滞，这表明跨物种的哺乳动物 PSC 的基本生物过程是保守的。然而，尽管调控网络整体保守，我们发现核心调控元件的下游靶点和经过正选择的特定氨基酸残基快速进化。我们的数据表明谱系特异性多能性调节网络的发展可以解释观察到的哺乳动物 PSC 某些特征的变化。我们进一步揭示，积极选择的基因可能与物种独特的适应特征相关，而这些特征并不专用于 PSC 的调节。这些结果为了解哺乳动物 PSC 特征变化背后的多能性基因调控网络的进化提供了重要的见解。