Comparisons of the genome of SARS-CoV-2 and those of other betacoronaviruses

Abstract

AbstractThe genome of SARS-CoV-2 virus causing the worldwide pandemic of COVID-19 is most closely related to viral metagenomes isolated from bats and, more distantly, pangolins. All are of sarbecoviruses of the genus Betacoronavirus. We have unravelled their recombinational and mutational histories. All showed clear evidence of recombination, most events involving the 3’ half of the genomes. The 5’ region of their genomes was mostly recombinant free, and a phylogeny calculated from this region confirmed that SARS-CoV-2 is closer to RmYN02 than RaTG13, and showed that SARS-CoV-2 diverged from RmYN02 at least 26 years ago, and both diverged from RaTG13 at least 37 years ago; recombinant regions specific to these three viruses provided no additional information as they matched no other Genbank sequences closely. Simple pairwise comparisons of genomes show that there are three regions where most non-synonymous changes probably occurred; the DUF3655 region of the nsp3, the S gene and ORF 8 gene. Differences in the last two of those regions have probably resulted from recombinational changes, however differences in the DUF3655 region may have resulted from selection. A hexamer of the proteins encoded by the nsp3 region may form the molecular pore spanning the double membrane of the coronavirus replication organelle (Wolff et al., 2020), and perhaps the acidic polypeptide encoded by DUF3655 lines it, and presents a novel target for pharmaceutical intervention.