SARS-CoV-2, the causative agent of COVID-19, has an RNA genome, which is, overall, closely related to the bat coronavirus sequence RaTG13. However, the ACE2-binding domain of this virus is more similar to a coronavirus isolated from a Guangdong pangolin. In addition to this unique feature, the genome of SARS-CoV-2 (and its closely related coronaviruses) has a low CpG content. This has been postulated to be the signature of an evolutionary pressure exerted by the host antiviral protein ZAP. Here, we analyzed the sequences of a wide range of viruses using both alignment-based and alignment free approaches to investigate the origin of SARS-CoV-2 genome. Our analyses revealed a high level of similarity between the 5UTR of SARS-CoV-2 and that of the Guangdong pangolin coronavirus. This suggests bat and pangolin coronaviruses might have recombined at least twice (in the 5UTR and ACE2 binding regions) to seed the formation of SARS-CoV-2. An alternative hypothesis is that the lineage preceding SARS-CoV-2 is a yet to be sampled bat coronavirus whose ACE2 binding domain and 5UTR are distinct from other known bat coronaviruses. Additionally, we performed a detailed analysis of viral genome compositions as well as expression and RNA binding data of ZAP to show that the low CpG abundance in SARS-CoV-2 is not related to an evolutionary pressure from ZAP.

中文翻译：

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SARS-CoV-2基因组中ZAP依赖性CpG降低的证据，以及5'UTR穿山甲冠状病毒的起源

SARS-CoV-2（COVID-19的病原体）具有一个RNA基因组，该基因组总体上与蝙蝠冠状病毒序列RaTG13密切相关。但是，该病毒的ACE2结合域与从穿山甲中分离出的冠状病毒更为相似。除此独特功能外，SARS-CoV-2（及其紧密相关的冠状病毒）的基因组还具有较低的CpG含量。据推测，这是宿主抗病毒蛋白ZAP施加进化压力的标志。在这里，我们使用基于比对和无比对的方法分析了各种病毒的序列，以研究SARS-CoV-2基因组的起源。我们的分析显示，SARS-CoV-2的5UTR与广东穿山甲冠状病毒的5UTR具有高度的相似性。这些数据表明，不仅ACE2，但SARS-CoV-2的5UTR也可能是穿山甲冠状病毒的起源。此外，我们对病毒基因组组成以及ZAP的表达和RNA结合数据进行了详细分析，以显示SARS-CoV-2中低的CpG丰度与ZAP的进化压力无关。