Progressive Evolutionary Dynamics of Gene-Specific ω Led to the Emergence of Novel SARS-CoV-2 Strains Having Super-Infectivity and Virulence with Vaccine Neutralization.

An estimation of the proportion of nonsynonymous to synonymous mutation (dn/ds, ω) of the SARS-CoV-2 genome would indicate the evolutionary dynamics necessary to evolve into novel strains with increased infection, virulence, and vaccine neutralization. A temporal estimation of ω of the whole genome, and all twenty-nine SARS-CoV-2 genes of major virulent strains of alpha, delta and omicron demonstrates that the SARS-CoV-2 genome originally emerged (ω ~ 0.04) with a strong purifying selection (ω < 1) and reached (ω ~ 0.85) in omicron towards diversifying selection (ω > 1). A marked increase in the ω occurred in the spike gene from alpha (ω = 0.2) to omicron (ω = 1.97). The ω of the replication machinery genes including RDRP , NSP3 , NSP4 , NSP7 , NSP8 , NSP10 , NSP13 , NSP14 , and ORF9 are markedly increased, indicating that these genes/proteins are yet to be evolutionary stabilized and are contributing to the evolution of novel virulent strains. The delta-specific maximum increase in ω in the immunomodulatory genes of NSP8 , NSP10 , NSP16 , ORF4 , ORF5 , ORF6 , ORF7A , and ORF8 compared to alpha or omicron indicates delta-specific vulnerabilities for severe COVID-19 related hospitalization and death. The maximum values of ω are observed for spike ( S ), NSP4 , ORF8 and NSP15 , which indicates that the gene-specific temporal estimation of ω identifies specific genes for its super-infectivity and virulency that could be targeted for drug development.