The use of SARS-CoV-2-related coronaviruses from bats and pangolins to polarize mutations in SARS-Cov-2
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e use of SARS-CoV-2-related coronaviruses from bats and pangolins to polarize mutations in SARS-Cov-2 1
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Tao Li , Xiaolu Tang , Changcheng Wu , Xinmin Yao , Yirong Wang , Xuemei Lu 2* & Jian Lu 1
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology; Center for Excellence in Animal Evolution and 2
Genetics, Chinese Academy of Sciences, Kunming 650223, China; State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, School of Life Sciences, Peking University, Beijing 100871, China Received May 20, 2020; accepted June 22, 2020; published online July 1, 2020
Citation:
Li, T., Tang, X., Wu, C., Yao, X., Wang, Y., Lu, X., and Lu, J. (2020). The use of SARS-CoV-2-related coronaviruses from bats and pangolins to polarize mutations in SARS-Cov-2. Sci China Life Sci 63, https://doi.org/10.1007/s11427-020-1764-2
Dear Editor, The coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 coronavirus has become a global pandemic. The SARS-CoV-2 genome has a similarity of 96.2% to that of RaTG13, a bat SARS-CoV-2-related coronavirus detected in Rhinolophus affinis (Paraskevis et al., 2020; Zhou et al., 2020). The SARS-CoV-2 genome also has 85.5%−92.4% sequence similarity to SARS-CoV-2-related coronaviruses from Malayan pangolins that have been seized in antismuggling operations in southern China (Guangdong-Pangolin (GD-Pangolin-CoV) and Guangxi-Pangolin (GX-Pangolin-CoV) genomes) (Liu et al., 2019; Lam et al., 2020). Although the genomic sequences of SARS-CoV-2 viruses share a similarity of greater than 99.9% (Lu et al., 2020; Ren et al., 2020; Zhou et al., 2020), hundreds of genetic variants have been identified across different SARS-CoV-2 strains (Forster et al., 2020; Tang et al., 2020; Yu et al., 2020). Several groups have used SARS-CoV-2-related coronavirus from bats and pangolins as outgroups to polarize the ancestral and derived mutations across SARS-CoV-2 strains (Forster et al., 2020; Tang et al., 2020; Yu et al., 2020); *Corresponding authors (Jian Lu, email: [email protected]; Xuemei Lu, email: [email protected])
however, the accuracy of such ancestral inferences remains unclear. To address this issue, we conducted forward simulations of the molecular evolution of viral genomes by incorporating mutations and natural selection. We modeled viral evolution as a stochastic Markov chain process. We assumed that: (i) 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; (ii) N3 and N4 are two randomly chosen strains descending from N2; and (iii) the viruses evolved in a stochastic process, and both mutation and selection occurred during each time unit (Figure 1A). The nucleotides of N1, N3, and N4 can be determined by genome sequencing. Although the nucleotides of both N0 and N2 are unknown, we can infer the N2 nucleotide states by comparing N1, N3, and N4 using the maximum parsimony (MP) method (N
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