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Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13

Longxian Lv, Gaolei Li, Jinhui Chen, Xinle Liang, Yudong Li
doi: https://doi.org/10.1101/2020.02.27.969006
Longxian Lv
1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University
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Gaolei Li
2Department of Biological Engineering, School of Food Science and Biotechnology, Zhejiang Gongshang Univeristy, Hangzhou 310018, China
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Jinhui Chen
3College of Biological and Chemical Engineering, Jiaxing University, Jiaxing 314001, China
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Xinle Liang
2Department of Biological Engineering, School of Food Science and Biotechnology, Zhejiang Gongshang Univeristy, Hangzhou 310018, China
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Yudong Li
2Department of Biological Engineering, School of Food Science and Biotechnology, Zhejiang Gongshang Univeristy, Hangzhou 310018, China
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  • For correspondence: lyd@zjsu.edu.cn
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Abstract

The novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3’-to-5’ exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted March 02, 2020.
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Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13
Longxian Lv, Gaolei Li, Jinhui Chen, Xinle Liang, Yudong Li
bioRxiv 2020.02.27.969006; doi: https://doi.org/10.1101/2020.02.27.969006
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Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13
Longxian Lv, Gaolei Li, Jinhui Chen, Xinle Liang, Yudong Li
bioRxiv 2020.02.27.969006; doi: https://doi.org/10.1101/2020.02.27.969006

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