The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human-emerged virus of the 21st century from the Coronaviridae family, causing the ongoing coronavirus disease 2019 (COVID-19) pandemic. Due to the high zoonotic potential of coronaviruses, it is critical to unravel their evolutionary history of host species breadth, host-switch potential, adaptation and emergence, to identify viruses posing a pandemic risk in humans. We present here a comprehensive analysis of the composition and codon usage bias of the 82 Orthocoronavirinae members, infecting 47 different avian and mammalian hosts. Our results clearly establish that synonymous codon usage varies widely among viruses, is only weakly dependent on their primary host, and is dominated by mutational bias towards AU-enrichment and by CpG avoidance. Indeed, variation in GC3 explains around 34%, while variation in CpG frequency explains around 14% of total variation in codon usage bias. Further insight on the mutational equilibrium within Orthocoronavirinae revealed that most coronavirus genomes are close to their neutral equilibrium, the exception being the three recently infecting human coronaviruses, which lie further away from the mutational equilibrium than their endemic human coronavirus counterparts. Finally, our results suggest that, while replicating in humans, SARS-CoV-2 is slowly becoming AU-richer, likely until attaining a new mutational equilibrium.

中文翻译：

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冠状病毒中密码子使用的变异主要是由 CpG 二核苷酸的突变偏差和选择性约束驱动的

在严重急性呼吸综合征冠状2（SARS-COV-2）是从21世纪的第三人出现病毒的冠状病毒家族，导致正在进行的冠状病毒病2019（COVID-19）的大流行。由于冠状病毒具有很高的人畜共患病潜力，因此必须解开它们在宿主物种广度、宿主转换潜力、适应和出现方面的进化历史，以确定对人类造成大流行风险的病毒。我们在此对 82 个正冠状病毒亚科的组成和密码子使用偏差进行了全面分析成员，感染 47 种不同的鸟类和哺乳动物宿主。我们的结果清楚地表明，同义密码子的使用在病毒之间差异很大，仅微弱地依赖于它们的主要宿主，并且主要是对 AU 富集的突变偏向和 CpG 的回避。事实上，GC3 的变异解释了大约 34%，而 CpG 频率的变异解释了密码子使用偏差总变异的 14%。进一步了解正冠状病毒亚科内的突变平衡揭示大多数冠状病毒基因组接近其中性平衡，但最近感染的三种人类冠状病毒除外，它们比地方性人类冠状病毒更远离突变平衡。最后，我们的结果表明，虽然在人类中进行复制，但 SARS-CoV-2 正慢慢变得富含 AU，可能直到达到新的突变平衡。