Mutation signature of SARS-CoV-2 variants raises questions to their natural origins.

SARS-CoV-2 variants, such as Omicron, have acquired a number of mutations. These novel mutations have raised concerns regarding the continued efficacy of the antibodies generated in response to vaccination. In this study I show that the evolution of the SARS-CoV-2 variant Omicron, does not appear to follow a Darwinian trajectory. The mutations in the Omicron variant are heavily biased toward nonsynonymous substitutions rather than synonymous substitutions. Interestingly, mutations affecting the spike gene of the Omicron variant are almost exclusively nonsynonymous. Moreover, a nonsynonymous substitution bias within spike gene is a common feature of all of the SARS-CoV-2 variants assessed in this study. This mutational signature is a counter-evidence of neutral evolution, and shows that the spike genes of these SARS-CoV-2 variants have evolved without trial-and-error by mutation and selection. Thus I postulate that the spike genes of these SARS-CoV-2 variants are not the result of natural evolution but rather designed molecules.