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

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.