Evolutionary shift from purifying selection towards divergent selection of SARS-CoV2 favors its invasion into multiple human organs

Abstract

SARS-CoV2 virus is believed to be originated from a closely related bat Coronavirus RaTG13 lineage and uses its key entry-point residues in S1 protein to attach with human ACE2 receptor. SARS-CoV2 could enter human from bat with its poorly developed entry-point residues much before its known appearance with slower mutation rate or recently with efficiently developed entry-point residues with higher mutation rate or through an intermediate host. Temporal analysis of SARS-CoV2 genome shows that its nucleotide substitution rate is as low as 27nt/year with an evolutionary rate of 9×10−4/site/year, which is well within the range of other RNA virus (10−4 to 10−6/site/year). TMRCA of SARS-CoV2 from bat RaTG13 lineage appears to be in between 9 and 14 years. Evolution of a critical entry-point residue Y493Q needs two substitutions with an intermediate virus carrying Y493H (Y>H>Q) but has not been identified in known twenty-nine bat CoV virus. Genetic codon analysis indicates that SARS-CoV2 evolution during propagation in human disobeys neutral evolution as nonsynonymous mutations surpass synonymous mutations with the increase of ω (dn/ds). Taken together, genetic data suggests that SARS-CoV2 is originated long time back before its appearance in human in 2019. Increase of ω signifies that SARs-CoV2 evolution is approaching towards diversifying selection from purifying selection predictably for its infection power to evade multiple human organs.