The origin and underlying driving forces of the SARS-CoV-2 outbreak

  1. Shu-Miaw Chaw
  2. Jui-Hung Tai
  3. Shi-Lun Chen
  4. Chia-Hung Hsieh
  5. Sui-Yuan Chang
  6. Shiou-Hwei Yeh
  7. Wei-Shiung Yang
  8. Pei-Jer Chen
  9. Hurng-Yi Wang

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Abstract

The spread of SARS-CoV-2 since December 2019 has become a pandemic and impacted many aspects of human society. Here, we analyzed genetic variation of SARS-CoV-2 and its related coronavirus and found the evidence of intergenomic recombination. After correction for mutational bias, analysis of 137 SARS-CoV-2 genomes as of 2/23/2020 revealed the excess of low frequency mutations on both synonymous and nonsynonymous sites which is consistent with recent origin of the virus. In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China was two time higher than those derived from the rest of the world. In addition, in network analysis, haplotypes collected from Wuhan city were at interior and have more mutational connections, both of which are consistent with the observation that the outbreak of cov-19 was originated from China.

SUMMARY

In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated.

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    SciScore for 10.1101/2020.04.12.038554: (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
    Sequence analyses and phylogeny construction: CDSs were aligned based on translated amino acid sequences using MUSCLE v3.8.31 [40], and back-translated to their corresponding DNA sequences using TRANALIGN software from the EMBOSS package (http://emboss.open-bio.org/) [41].
    MUSCLE
    suggested: (MUSCLE, RRID:SCR_011812)
    EMBOSS
    suggested: (EMBOSS, RRID:SCR_008493)
    Number of nonsynonymous changes per nonsynonymous site (dN) and synonymous changes per synonymous site (dS) among genomes were estimated based Li-Wu-Luo’s method [45] implemented in MEGA-X and PAML 4 [46].
    PAML
    suggested: (PAML, RRID:SCR_014932)
    The RDP file for the haplotype network analyses was generated using DnaSP 6.0 [47] and input into Network 10 (https://www.fluxus-engineering.com/) to construct the haplotype network using the median joining algorithm.
    https://www.fluxus-engineering.com/
    suggested: (Fluxus Engineering, RRID:SCR_008618)
    Four haplotype test implemented in DnaSp was applied to test for possible recombination event.
    DnaSp
    suggested: (DnaSP, RRID:SCR_003067)
    The mutation rate of SARS-CoV-2 and the time to the most recent common ancestor (TMRCA) of virus isolates were estimated by an established Bayesian MCMC approach implemented in BEAST version 1.10.4 [48].
    BEAST
    suggested: (BEAST, RRID:SCR_010228)

    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:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • 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.

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  2. Version published to 10.1101/2020.04.12.038554 on bioRxiv