Recombination in sarbecovirus lineage and mutations/insertions in spike protein are linked to the emergence and adaptation of SARS-CoV-2

  1. Centre of Bioinformatics, Institute of Interdisciplinary Studies, University of Allahabad, Prayagraj – 211002, India
  2. Anup Som

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Abstract

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan city, China in December 2019 and thereafter its spillover across the world has created a global pandemic and public health crisis. Right after, there has been intense interest in understanding how the SARS-CoV-2 originated and evolved. This paper also aims to shed light on the origin and evolution of SARS-CoV-2. A consensus result based on whole genome phylogeny, gene tree analysis, and genetic similarity study revealed that SARS-CoV-2 evolved from Bat-CoV-RaTG13. Furthermore, recombination analysis indicated that probable origin of SARS-CoV-2 is the results of ancestral intra-species recombination events between bat coronaviruses belonging to Sarbecovirus sub-genus. Multiple sequence alignment (MSA) revealed the insertion of four amino acid residues “PRRA” (Proline-Arginine-Arginine-Alanine) to the S1/S2 site in the spike protein of SARS-CoV-2, and structural modeling of spike protein of bat-CoV-RaTG13 also shows a high number of mutations at one of the receptor binding domains (RBD). Acquisition of the furin cleavage sites (“PRRA”) along with high number of mutations at one of its RBD is probably responsible for the adaptation of SARS-CoV-2 into human systems. Furthermore, the codon adaptation index (CAI) was used to quantify the magnitude of adaptive efficacy of SARS-CoV-2 in human host in comparison with SARS-CoV. The CAI result showed a relatively less adaptive efficacy of the newly emerged SARS-CoV-2 to the human systems, which might be an indication of its mild clinical severity and progression compared to SARS-CoVs.

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  1. Version published to 10.6026/97320630018951
  2. Version published to 10.1101/2020.05.12.091199v2 on bioRxiv
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    SciScore for 10.1101/2020.05.12.091199: (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
    Data selection: 162 Orthocoronavirinae genomes were retrieved from NCBI (https://www.ncbi.nlm.nih.gov/) and Virus Pathogen Database and Analysis Resource (https://www.viprbrc.org/).
    https://www.ncbi.nlm.nih.gov/
    suggested: (GENSAT at NCBI - Gene Expression Nervous System Atlas, RRID:SCR_003923)
    Phylogenetic reconstruction: The genome sequences were aligned using the MAFFT alignment tool (Katoh et al., 2002).
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    Trees were reconstructed using IQ-TREE software (Nguyen et al., 2015) and were visualized with iTOL software (Letunic et al., 2019).
    IQ-TREE
    suggested: (IQ-TREE, RRID:SCR_017254)

    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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  4. Version published to 10.1101/2020.05.12.091199v1 on bioRxiv