Codon usage pattern reveals SARS-CoV-2 as a monomorphic pathogen of hybrid origin with role of silent mutations in rapid evolutionary success

Abstract

Viruses are dependent on the host tRNA pool, and an optimum codon usage pattern (CUP) is a driving force in its evolution. Systematic analysis of CUP of replicase (rdrp), spike, envelope (E), membrane glycoprotein (M), and nucleocapsid (N) encoding genes of SARS-CoV-2 from reported diverse lineages to suggest one-time host jump of a SARS-CoV-2 isolate into the human host. In contrast to human isolates, a high degree of variation in CUP of these genes suggests that bats, pangolins, and dogs are natural reservoirs of diverse strains. At the same time, our analysis suggests that dogs are not a source of SARS-CoV-2. Interestingly, CUP of rdrp displays conservation with two bat SARS isolates RaTG13 and RmYN02. CUP of the SARS-CoV-2 E gene is also conserved with bat and pangolin isolates with variations for a few amino acids. This suggests role allele replacement in these two genes involving SARS strains of least two hosts. At the same time, a relatively conserved CUP pattern in replicase and envelope across hosts suggests them it to be an ideal target in antiviral development for SARS-CoV-2.

Mutational cascade of SARS-CoV-2 leading to evolution and emergence of omicron variant

“…Globally, high risk of reinfection with omicron variant, low vaccine and testing coverage are ideal for mutations resulting in the emergence of new variants of SARS-CoV-2 (Pulliam et al, 2021). Since COVID-19 inception, researchers have been trying to investigate its origin and evolution (Bansal, Kumar, & Patil, 2021; Singh & Soojin, 2021; Tang et al, 2020). We are currently witnessing a global molecular arms race between SARS-CoV-2 and its preventive therapeutics based on diverse regimes such as DNA, RNA, protein or inactivated whole-virion, etc.…”