Temporal evolution and adaptation of SARS-CoV-2 codon usage.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first occurred in Wuhan (China) in December of 2019. Since the outbreak, it has accumulated mutations on its coding sequences to optimize its adaptation to the human host. The identification of its genetic variants has become crucial in tracking and evaluating their spread across the globe. Methods: In this study, we compared 320,338 SARS-CoV-2 genomes isolated from all over the world to the first sequenced genome in Wuhan, China. To this end, we analysed over time the codon usage patterns of SARS-CoV-2 genes encoding for the membrane protein (M), envelope (E), spike surface glycoprotein (S), nucleoprotein (N), RNA-dependent RNA polymerase (RdRp) and ORF1ab. Results: We found that genes coding for the proteins N and S diverged more rapidly since the outbreak by accumulating mutations. Interestingly, all genes show a deoptimization of their codon usage with respect to the human host. Our findings suggest a general evolutionary trend of SARS-CoV-2, which evolves towards a sub-optimal codon usage bias to favour the host survival and its spread. Furthermore, we found that S protein and RdRp are more subject to an increasing purifying pressure over time, which implies that these proteins will reach a lower tendency to accept mutations. In contrast, proteins N and M tend to evolve more under the action of mutational bias, thus exploring a large region of their sequence space. Conclusions: Overall, our study shed more light on the evolution of SARS-CoV-2 genes and their adaptation to humans, helping to foresee their mutation patterns and the emergence of new variants