Abstract The recent emergence of SARS-CoV-2 is responsible for the current pandemic of COVID-19, which uses the human membrane protein ACE2 as a gateway to host-cell infection. We performed a comparative genomic analysis of 70 ACE2 placental mammal orthologues to identify variations and contribute to the understanding of evolutionary dynamics behind this successful adaptation to infect humans. Our results reveal that 4% of the ACE2 sites are under positive selection, all located in the catalytic domain, suggesting possibly taxon-specific adaptations related to the ACE2 function, such as cardiovascular physiology. Considering all variable sites, we selected 30 of them located at the critical ACE2 binding sites to the SARS-CoV-like viruses for analysis in more detail. Our results reveal a relatively high diversity of ACE2 between placental mammal species, while showing no polymorphism within human populations, at least considering the 30 inter-species variable sites. A perfect scenario for natural selection favored this opportunistic new coronavirus in its trajectory of infecting humans. We suggest that SARS-CoV-2 became a specialist coronavirus for human hosts. Differences in the rate of infection and mortality could be related to the innate immune responses, other unknown genetic factors, as well as non-biological factors.

中文翻译：

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胎盘哺乳动物ACE2多样性揭示了SARS-CoV-2的进化策略

摘要 最近出现的 SARS-CoV-2 是当前 COVID-19 大流行的原因，它使用人膜蛋白 ACE2 作为宿主细胞感染的途径。我们对 70 个 ACE2 胎盘哺乳动物直系同源物进行了比较基因组分析，以识别变异并有助于理解这种成功适应感染人类背后的进化动力学。我们的结果显示 4% 的 ACE2 位点处于正选择之下，全部位于催化域，这表明可能与 ACE2 功能相关的分类群特异性适应，例如心血管生理学。考虑到所有可变位点，我们选择了其中 30 个位于与 SARS-CoV 样病毒的关键 ACE2 结合位点进行更详细的分析。我们的结果揭示了胎盘哺乳动物物种之间 ACE2 的相对较高的多样性，同时在人类种群中没有显示多态性，至少考虑到 30 个物种间可变位点。自然选择的完美场景有利于这种机会主义的新型冠状病毒感染人类的​​轨迹。我们建议 SARS-CoV-2 成为人类宿主的一种特殊冠状病毒。感染率和死亡率的差异可能与先天免疫反应、其他未知遗传因素以及非生物因素有关。我们建议 SARS-CoV-2 成为人类宿主的一种特殊冠状病毒。感染率和死亡率的差异可能与先天免疫反应、其他未知遗传因素以及非生物因素有关。我们建议 SARS-CoV-2 成为人类宿主的一种特殊冠状病毒。感染率和死亡率的差异可能与先天免疫反应、其他未知遗传因素以及非生物因素有关。