The Novel Coronavirus Enigma: Phylogeny and Analyses of Coevolving Mutations Among the SARS-CoV-2 Viruses Circulating in India

  1. Anindita Banerjee
  2. Rakesh Sarkar
  3. Suvrotoa Mitra
  4. Mahadeb Lo
  5. Shanta Dutta
  6. Mamta Chawla-Sarkar

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Abstract

The RNA genome of the emerging novel coronavirus is rapidly mutating, and its human-to-human transmission rate is increasing. Hence, temporal dissection of their evolutionary dynamics, the nature of variations among different strains, and understanding the single nucleotide polymorphisms in the endemic settings are crucial. Delineating the heterogeneous genomic constellations of this novel virus will help us understand its complex behavior in a particular geographical region.

Objective

This is a comprehensive analysis of 95 Indian SARS-CoV-2 genome sequences available from the Global Initiative on Sharing All Influenza Data (GISAID) repository during the first 6 months of 2020 (January through June). Evolutionary dynamics, gene-specific phylogeny, and the emergence of the novel coevolving mutations in 9 structural and nonstructural genes among circulating SARS-CoV-2 strains across 12 different Indian states were analyzed.

Methods

A total of 95 SARS-CoV-2 nucleotide sequences submitted from India were downloaded from the GISAID database. Molecular Evolutionary Genetics Analysis, version X software was used to construct the 9 phylogenetic dendrograms based on nucleotide sequences of the SARS-CoV-2 genes. Analyses of the coevolving mutations were done in comparison to the prototype SARS-CoV-2 from Wuhan, China. The secondary structure of the RNA-dependent RNA polymerase/nonstructural protein NSP12 was predicted with respect to the novel A97V mutation.

Results

Phylogenetic analyses revealed the evolution of “genome-type clusters” and adaptive selection of “L”-type SARS-CoV-2 strains with genetic closeness to the bat severe acute respiratory syndrome–like coronaviruses. These strains were distant to pangolin or Middle East respiratory syndrome–related coronavirus strains. With regard to the novel coevolving mutations, 2 groups have been seen circulating in India at present, the “major group” (66/95, 69.4%) and the “minor group” (21/95, 22.1%) , harboring 4 and 5 coexisting mutations, respectively. The “major group” mutations fall in the A2a clade. All the minor group mutations, except 11083G>T (L37F, NSP6 gene), were unique to the Indian isolates.

Conclusions

This study highlights the rapidly evolving SARS-CoV-2 virus and the cocirculation of multiple clades and subclades. This comprehensive study is a potential resource for monitoring the novel mutations in the viral genome, interpreting changes in viral pathogenesis, and designing vaccines or other therapeutics.

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  1. Version published to 10.2196/20735
  2. ScreenIT

    SciScore for 10.1101/2020.05.25.114199: (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
    Multiple sequence alignment for all the respective set of gene sequences was done using MUSCLE v3.8.31.
    MUSCLE
    suggested: (MUSCLE, RRID:SCR_011812)
    Phylogenetic dendrograms were constructed by MEGA, version X (Molecular Evolutionary Genetics Analysis), using the maximum-likelihood statistical method (at 1000 bootstrap replicates), using the best fit nucleotide substitution models for each dendrogram.
    MEGA
    suggested: (Mega BLAST, RRID:SCR_011920)

    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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  3. Version published to 10.2196/preprints.20735
  4. Version published to 10.1101/2020.05.25.114199v1 on bioRxiv