Temporal evolution and adaptation of SARS-COV-2 codon usage

The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has caused an unprecedented pandemic. Since the first sequenced whole-genome of SARS-CoV-2 on January 2020, the identification of its genetic variants has become crucial in tracking and evaluating their spread across the globe.

In this study, we compared 134,905 SARS-CoV-2 genomes isolated from all affected countries since the outbreak of this novel coronavirus with the first sequenced genome in Wuhan, China to quantify the evolutionary divergence of SARS-CoV-2. Thus, we compared the codon usage patterns of SARS-CoV-2 genes encoding the membrane protein (M), envelope (E), spike surface glycoprotein (S), nucleoprotein (N), RNA-dependent RNA polymerase (RdRp). The polyproteins ORF1a and ORF1b were examined separately.

We found that SARS-CoV-2 tends to diverge over time by accumulating mutations on its genome and, specifically, on the sequences encoding proteins N and S. Interestingly, different patterns of codon usage were observed among these genes. GenesSandNtend to use a narrower set of synonymous codons that are better optimized to the human host. Conversely, genesEandMconsistently use the broader set of synonymous codons, which does not vary in respect to the reference genome. CAI and SiD time evolutions show a tendency to decrease that emerge for most genes. Forsdyke plots are used to study the nature of mutations and they show a rapid evolutionary divergence of each gene, due to the low values of x-intercepets.