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Leto 2021

Hongru Wang, Lenore Pipes, Rasmus Nielsen. Synonymous mutations and the molecular evolution of SARS-CoV-2 origins. Virus Evol, 7(1):veaa098. 2021.

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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 dN /dS 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.