Synonymous mutations and the molecular evolution of SARS-CoV-2 origins
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Synonymous mutations and the molecular evolution of SARS-CoV-2 origins. / Wang, Hongru; Pipes, Lenore; Nielsen, Rasmus.
In: Virus Evolution, Vol. 7, No. 1, veaa098, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Synonymous mutations and the molecular evolution of SARS-CoV-2 origins
AU - Wang, Hongru
AU - Pipes, Lenore
AU - Nielsen, Rasmus
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - SARS-CoV-2
KW - synonymous mutations
KW - molecular evolution
U2 - 10.1093/ve/veaa098
DO - 10.1093/ve/veaa098
M3 - Journal article
C2 - 33500788
VL - 7
JO - Virus Evolution
JF - Virus Evolution
SN - 2057-1577
IS - 1
M1 - veaa098
ER -
ID: 272321521