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 from Rhinolophus 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 (~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.
【저자키워드】 Evolution, SARS-CoV-2, coronavirus, CpG depletion, cytosine deamination, mutation bias, 【초록키워드】 SARS-CoV2, pandemic, Mutation, Human, variant, SARS-CoV-2 peptides, virus, Spread, RaTG13, substitutions, genomes, CpG, Frequency, other coronaviruses, transfer, hosts, Substitution, codon, human SARS-CoV-2, single nucleotide variation, coronavirus genomes, genome structure, isolate, Deamination, analyzed, caused, evaluated, exhibited, C>U mutation, hydrophobic amino acid, the SARS-CoV-2, 【제목키워드】 Human, RaTG13, Rapid, bat, pattern,