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

  1. Longxian Lv
  2. Gaolei Li
  3. Jinhui Chen
  4. Xinle Liang
  5. Yudong Li

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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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    SciScore for 10.1101/2020.02.27.969006: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Phylogenetic analysis: Genome sequences were aligned using MUSCLE v3.8.31 (9), followed by manual adjustment using BioEdit v7.2.5.
    MUSCLE
    suggested: (MUSCLE, RRID:SCR_011812)
    BioEdit
    suggested: (BioEdit, RRID:SCR_007361)
    Phylogenetic analyses of complete genome were performed using maximum-likelihood method and general time-reversible model of nucleotide substitution with gamma-distributed rates among sites (GTR+G) in RAxML v8.1.21 (10).
    RAxML
    suggested: (RAxML, RRID:SCR_006086)
    Phylogenetic analyses of coding sequences were performed using MEGA-X software.
    MEGA-X
    suggested: None
    Estimation of synonymous and non-synonymous substitution rates: The number of synonymous substitutions per synonymous site (dS), and the number of non-synonymous substitutions per non-synonymous site (dN), for each coding region were calculated using the Nei-Gojobori method (Jukes-Cantor) in PAML package (12).
    PAML
    suggested: (PAML, RRID:SCR_014932)
    The adaptive evolution server (http://www.datamonkey.org/) was used to identify eventual sites of positive selection.
    http://www.datamonkey.org/
    suggested: (DataMonkey, RRID:SCR_010278)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.02.27.969006 on bioRxiv