Abstract Human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related, by average genetic distance, to two coronaviruses isolated from bats, RaTG13 and RmYN02. However, there is a segment of high amino acid similarity between human SARS-CoV-2 and a pangolin-isolated strain, GD410721, in the receptor-binding domain (RBD) of the spike protein, a pattern that can be caused by either recombination or by convergent amino acid evolution driven by natural selection. We perform a detailed analysis of the synonymous divergence, which is less likely to be affected by selection than amino acid divergence, between human SARS-CoV-2 and related strains. We show that the synonymous divergence between the bat-derived viruses and SARS-CoV-2 is larger than between GD410721 and SARS-CoV-2 in the RBD, providing strong additional support for the recombination hypothesis. However, the synonymous divergence between pangolin strain and SARS-CoV-2 is also relatively high, which is not consistent with a recent recombination between them, instead, it suggests a recombination into RaTG13. We also find a 14-fold increase in the d N / d S ratio from the lineage leading to SARS-CoV-2 to the strains of the current pandemic, suggesting that the vast majority of nonsynonymous mutations currently segregating within the human strains have a negative impact on viral fitness. Finally, we estimate that the time to the most recent common ancestor of SARS-CoV-2 and RaTG13 or RmYN02 based on synonymous divergence is 51.71 years (95% CI, 28.11–75.31) and 37.02 years (95% CI, 18.19–55.85), respectively.
【저자키워드】 SARS-CoV-2, molecular evolution, synonymous mutations, 【초록키워드】 Evolution, coronavirus, pandemic, Human, Genetic, RBD, RmYN02, RaTG13, Lineage, Recombination, natural selection, Strains, bats, Amino acid, Hypothesis, Analysis, strain, similarity, Support, acute respiratory syndrome, 95% CI, average, viral fitness, human SARS-CoV-2, synonymous, nonsynonymous mutation, affected, caused, virus, coronavirus, majority, less, the spike protein, the RBD, the receptor-binding domain, increase in, driven by, 【제목키워드】 Evolution, Mutation, molecular,