Jiangsu Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China.
Jiangsu Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China
J Virol. 2020 Jul 30;94(16). doi: 10.1128/JVI.00684-20.
Viral receptors are the cell surface proteins that are hijacked by viruses to initialize their infections. Viral receptors are subject to two conflicting directional forces, namely, negative selection due to functional constraints and positive selection due to host-virus arms races. It remains largely obscure whether negative pleiotropy limits the rate of adaptation in viral receptors. Here, we perform evolutionary analyses of 96 viral receptor genes in primates and find that 41 out of 96 viral receptors experienced adaptive evolution. Many positively selected residues in viral receptors are located at the virus-receptor interfaces. Compared with control proteins, viral receptors exhibit significantly elevated rate of adaptation. Further analyses of genetic polymorphisms in human populations reveal signals of positive selection and balancing selection for 53 and 5 viral receptors, respectively. Moreover, we find that 49 viral receptors experienced different selection pressures in different human populations, indicating that viruses represent an important driver of local adaptation in humans. Our findings suggest that diverse viruses, many of which have not been known to infect nonhuman primates, have maintained antagonistic associations with primates for millions of years, and the host-virus conflicts drive accelerated adaptive evolution in viral receptors. Viruses hijack cellular proteins, termed viral receptors, to assist their entry into host cells. While viral receptors experience negative selection to maintain their normal functions, they also undergo positive selection due to an everlasting evolutionary arms race between viruses and hosts. A complete picture on how viral receptors evolve under two conflicting forces is still lacking. In this study, we systematically analyzed the evolution of 96 viral receptors in primates and human populations. We found around half of viral receptors underwent adaptive evolution and exhibit significantly elevated rates of adaptation compared to control genes in primates. We also found signals of past natural selection for 58 viral receptors in human populations. Interestingly, 49 viral receptors experienced different selection pressures in different human populations, indicating that viruses represent an important driver of local adaptation in humans. Our results suggest that host-virus arms races drive accelerated adaptive evolution in viral receptors.
病毒受体是被病毒劫持用于启动感染的细胞表面蛋白。病毒受体受到两种相互冲突的定向力的影响，即由于功能约束导致的负选择和由于宿主-病毒军备竞赛导致的正选择。病毒受体的负效多效性是否限制了其适应速度在很大程度上仍不清楚。在这里，我们对灵长类动物的 96 种病毒受体基因进行了进化分析，发现 96 种病毒受体中有 41 种经历了适应性进化。病毒受体中的许多正选择残基位于病毒-受体界面。与对照蛋白相比，病毒受体表现出明显更高的适应率。对人类群体中的遗传多态性的进一步分析揭示了 53 种和 5 种病毒受体分别经历了正选择和平衡选择的信号。此外，我们发现 49 种病毒受体在不同人群中经历了不同的选择压力，这表明病毒是人类局部适应的一个重要驱动因素。我们的研究结果表明，多种病毒与灵长类动物保持着对抗性的关联，其中许多病毒尚未被发现感染非灵长类动物，这种关联已经持续了数百万年，宿主-病毒的冲突导致了病毒受体的加速适应性进化。病毒劫持细胞蛋白，称为病毒受体，以协助其进入宿主细胞。虽然病毒受体经历负选择以维持其正常功能，但由于病毒和宿主之间不断进化的军备竞赛，它们也经历了正选择。目前，对于病毒受体在这两种相互冲突的力量下是如何进化的，我们仍然缺乏一个完整的认识。在这项研究中，我们系统地分析了灵长类动物和人类群体中 96 种病毒受体的进化。我们发现，大约一半的病毒受体经历了适应性进化，与灵长类动物中的对照基因相比，它们表现出明显更高的适应率。我们还在人类群体中发现了 58 种病毒受体过去自然选择的信号。有趣的是，49 种病毒受体在不同人群中经历了不同的选择压力，这表明病毒是人类局部适应的一个重要驱动因素。我们的研究结果表明，宿主-病毒的军备竞赛导致了病毒受体的加速适应性进化。
