Rapid molecular evolution across amniotes of the IIS/TOR network

Comparative analyses of central molecular networks uncover variation that can be targeted by biomedical research to develop insights and interventions into disease. The insulin/insulin-like signaling and target of rapamycin (IIS/TOR) molecular network regulates metabolism, growth, and aging. With the development of new molecular resources for reptiles, we show that genes in IIS/TOR are rapidly evolving within amniotes (mammals and reptiles, including birds). Additionally, we find evidence of natural selection that diversified the hormone-receptor binding relationships that initiate IIS/TOR signaling. Our results uncover substantial variation in the IIS/TOR network within and among amniotes and provide a critical step to unlocking information on vertebrate patterns of genetic regulation of metabolism, modes of reproduction, and rates of aging.针对核心分子网络的比较分析可发掘可被生物医学研究靶向利用的变异位点，进而为疾病相关研究提供理论洞见，并推动疾病干预手段的开发。胰岛素/胰岛素样信号通路与雷帕霉素靶蛋白分子网络（insulin/insulin-like signaling and target of rapamycin, IIS/TOR）调控机体代谢、生长与衰老进程。随着爬行动物新型分子研究资源的开发，本研究证实IIS/TOR通路相关基因在羊膜动物（哺乳类、爬行动物及鸟类）中呈现快速演化特征。此外，本研究还发现自然选择驱动启动IIS/TOR信号通路的激素-受体结合关系发生多样化分化的相关证据。本研究结果揭示了羊膜动物类群内部及不同类群间IIS/TOR网络存在的显著变异，为阐明脊椎动物代谢遗传调控模式、生殖方式及衰老速率相关研究提供了关键的研究基础。