Signatures of adaptive evolution during human to mink SARS CoV2 cross-species transmission inform estimates of the COVID19 pandemic timing

  1. Jui-Hung Tai
  2. Shu-Miaw Chaw
  3. Hsiao-Yu Sun
  4. Yi-Cheng Tseng
  5. Guanghao Li
  6. Sui-Yuan Chang
  7. Shiou-Hwei Yeh
  8. Pei-Jer Chen
  9. Hurng-Yi Wang

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Abstract

One of the unique features of SARS-CoV-2 is that it mainly evolved neutrally or under purifying selection during the early pandemic. This contrasts with the preceding epidemics of the closely related SARS-CoV and MERS-CoV, both of which evolved adaptively. It is possible that the SARS-CoV-2 exhibits a unique or adaptive feature which deviates from other coronaviruses. Alternatively, the virus may have been cryptically circulating in humans for a sufficient time to have acquired adaptive changes for efficient transmission before the onset of the current pandemic. In order to test the above scenarios, we analyzed the SARS-CoV-2 sequences from minks ( Neovision vision ) and parenteral human strains. In the early phase of the mink epidemic (April to May 2020), nonsynonymous to synonymous mutation ratios per site within the spike protein was 2.93, indicating a selection process favoring adaptive amino acid changes. In addition, mutations within this protein concentrated within its receptor binding domain and receptor binding motif. Positive selection also left a trace on linked neutral variation. An excess of high frequency derived variants produced by genetic hitchhiking was found during middle (June to July 2020) and early late (August to September 2020) phases of the mink epidemic, but quickly diminished in October and November 2020. Strong positive selection found in SARS-CoV-2 from minks implies that the virus may be not unique in super-adapting to a wide range of new hosts. The mink study suggests that SARS-CoV-2 already went through adaptive evolution in humans, and likely been circulating in humans at least six months before the first case found in Wuhan, China. We also discuss circumstances under which the virus can be well-adapted to its host but fail to induce an outbreak.

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    SciScore for 10.1101/2021.09.15.459215: (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 phylogenetic reconstruction: All sequences were aligned against the reference genome (EPI_ISL_402125) using the default settings in ClustalW [21].
    ClustalW
    suggested: (ClustalW, RRID:SCR_017277)
    Phylogenies were constructed using IQ-TREE 2.1.2 [22].
    IQ-TREE
    suggested: (IQ-TREE, RRID:SCR_017254)
    The ancestor sequences of SARS-CoV-2 and RaTG13 were reconstructed using codeml implemented in PAML 4 [26] under the free ratio model.
    PAML
    suggested: (PAML, RRID:SCR_014932)
    An array of selection detection methods implemented in HyPhy was applied to detect whether the lineage leading to minks has experienced adaptive evolution [27].
    HyPhy
    suggested: (HyPhy, RRID:SCR_016162)

    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.

    Results from scite Reference Check: We found no unreliable references.

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  2. Version published to 10.1101/2021.09.15.459215v1 on bioRxiv