A simple method for estimating time-irreversible nucleotide substitution rates in the SARS-CoV-2 genome

  1. Kazuharu Misawa
  2. Ryo Ootsuki

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Abstract

SARS-CoV-2 is the cause of the current worldwide pandemic of severe acute respiratory syndrome. The change of nucleotide composition of the SARS-CoV-2 genome is crucial for understanding the spread and transmission dynamics of the virus because viral nucleotide sequences are essential in identifying viral strains. Recent studies have shown that cytosine (C) to uracil (U) substitutions are overrepresented in SARS-CoV-2 genome sequences. These asymmetric substitutions between C and U indicate that traditional time-reversible substitution models cannot be applied to the evolution of SARS-CoV-2 sequences. Thus, we develop a new time-irreversible model of nucleotide substitutions to estimate the substitution rates in SARS-CoV-2 genomes. We investigated the number of nucleotide substitutions among the 7862 genomic sequences of SARS-CoV-2 registered in the Global Initiative on Sharing All Influenza Data (GISAID) that have been sampled from all over the world. Using the new method, the substitution rates in SARS-CoV-2 genomes were estimated. The C-to-U substitution rates of SARS-CoV-2 were estimated to be 1.95 × 10−3 ± 4.88 × 10−4 per site per year, compared with 1.48 × 10−4 ± 7.42 × 10−5 per site per year for all other types of substitutions.

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  1. Version published to 10.1093/nargab/lqae009
  2. Version published to 10.1101/2021.08.16.456444v4 on bioRxiv
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    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
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    Sequences were aligned using MAFFT (Katoh, et al.
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    suggested: (MAFFT, RRID:SCR_011811)

    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).

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    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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    Results from scite Reference Check: We found no unreliable references.

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  4. Version published to 10.1101/2021.08.16.456444v3 on bioRxiv
  5. Version published to 10.1101/2021.08.16.456444v2 on bioRxiv
  6. Version published to 10.1101/2021.08.16.456444v1 on bioRxiv