Mutation Patterns of Human SARS-CoV-2 and Bat RaTG13 Coronavirus Genomes Are Strongly Biased Towards C>U Transitions, Indicating Rapid Evolution in Their Hosts
Mutation Patterns of Human SARS-CoV-2 and Bat RaTG13 Coronavirus Genomes Are Strongly Biased Towards C>U Transitions, Indicating Rapid Evolution in Their Hosts
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DOI：
10.3390/genes11070761
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发表时间：
2020-07-01
期刊：
影响因子：
3.5
通讯作者：
Kovarik, Ales
中科院分区：
文献类型：
--
作者：
Matyasek, Roman;Kovarik, Ales
SARS-CoV-2的传播引起了人们对其进化起源和基因组结构的极大兴趣。在这里，我们分析了34个人类SARS-CoV-2分离株和从菊头蝠（一种菊头蝠）中分离的密切相关的RaTG 13的突变模式。我们还评估了SARS-CoV-2和其他人类和动物冠状病毒基因组中的CpG二核苷酸含量。在人类SARS-CoV-2和蝙蝠RaTG 13之间的1136个单核苷酸变异（类似于4%的差异）中，682个（60%）可归因于C>U和U>C取代，远远超过其他类型的取代。在人群中出现的SARS-CoV 2变异体中也观察到C>U突变的积累。在全球范围内，C>U取代增加了SARS-CoV-2肽段中疏水氨基酸密码子的频率，而U>C取代则降低了该频率。与大多数其他冠状病毒相比，SARS-CoV-2和RaTG 13在其基因组中均表现出CpG缺失。这些数据表明，由C脱氨基介导的C到U的转换在SARS-CoV-2冠状病毒的进化中发挥了重要作用。我们假设，高频率的C>U转换反映了病毒在其宿主中的适应过程，并且SARS-CoV-2在从动物转移到全球传播之前可能已经在人类中进化了相对较长的时间。
The pandemic caused by the spread of SARS-CoV-2 has led to considerable interest in its evolutionary origin and genome structure. Here, we analyzed mutation patterns in 34 human SARS-CoV-2 isolates and a closely related RaTG13 isolated fromRhinolophus affinis(a horseshoe bat). We also evaluated the CpG dinucleotide contents in SARS-CoV-2 and other human and animal coronavirus genomes. Out of 1136 single nucleotide variations (similar to 4% divergence) between human SARS-CoV-2 and bat RaTG13, 682 (60%) can be attributed to C>U and U>C substitutions, far exceeding other types of substitutions. An accumulation of C>U mutations was also observed in SARS-CoV2 variants that arose within the human population. Globally, the C>U substitutions increased the frequency of codons for hydrophobic amino acids in SARS-CoV-2 peptides, while U>C substitutions decreased it. In contrast to most other coronaviruses, both SARS-CoV-2 and RaTG13 exhibited CpG depletion in their genomes. The data suggest that C-to-U conversion mediated by C deamination played a significant role in the evolution of the SARS-CoV-2 coronavirus. We hypothesize that the high frequency C>U transitions reflect virus adaptation processes in their hosts, and that SARS-CoV-2 could have been evolving for a relatively long period in humans following the transfer from animals before spreading worldwide.