The use of SARS-CoV-2-related coronaviruses from bats and pangolins to polarize mutations in SARS-Cov-2

We would like to thank Drs. Chung-I Wu, Yaping Zhang, and Jindong Zhao for suggestive comments regarding this study. This work was supported by grants from the National Natural Science Foundation of China (U1902201) and the CAS Light of West China Program to X.L, and from the National Natural Science Foundation of China (91731301) to J.L.

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The author(s) declare that they have no conflict of interest.

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The supporting information is available online at https://doi.org/10.1007/s11427-020-1764-2. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Figure 1
The molecular evolution simulation and ancestral nucleotide inference. A, In the simulation, an ancestral virus N0 split into two lineages, one leading to N1 (resembling the outgroup) and the other leading to N2 (resembling the most recent common ancestor of the viral strains of interest). After t₂ days, N2 split into two lineages, N3 and N4. B, Examples showing whether the inferred N2 nucleotide state (N2′) based on the comparison of the nucleotides of N1, N3, and N4 matched the N2 nucleotide in the simulation. Correct (C), N2=N2′; Error (E), N2≠N2′; Uncertain (U), N2 cannot be inferred using the MP method. C, Sequence divergence between N1 and N3/N4 (y axis) increases as the evolutionary period (days) between N1 and N3/N4 (x axis) increases. D, The error rate for inferring the most recent common ancestor of N3 and N4 (y axis) increases as the divergence period (days) between N1 and N3/N4 increases (x axis). E, The uncertainty rate for inferring the most recent common ancestor of N3 and N4 (y axis) increases as the divergence period (days) between N1 and N3/N4 increases (x axis). The blue lines represent the synonymous sites, the red lines represent the overall sites, and the green lines represent the nonsynonymous sites. Lines in a darker color in (C–E) represent the mean value for 200 replications of the simulations. The left and right panels of (D) and (E) represent the results when the difference between N3 and N4 (θ) was 0.1% and 0.5%, respectively. The dashed lines represent the overall genomic similarity equivalent to that between RaTG13 and SARS-CoV-2.

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