Recombination in sarbecovirus lineage and mutations/insertions in spike protein are linked to the emergence and adaptation of SARS-CoV-2.

Abstract

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan city, China in December 2019 and thereafter its spillover across the world has created a global pandemic and public health crisis. Right after, there has been intense interest in understanding how the SARS-CoV-2 originated and evolved. This paper also aims to shed light on the origin and evolution of SARS-CoV- 2. A consensus result based on whole genome phylogeny, gene tree analysis, and genetic similarity study revealed that SARS-CoV-2 evolved from Bat-CoV-RaTG13. Furthermore, recombination analysis indicated that probable origin of SARS-CoV-2 is the results of ancestral intra-species recombination events between bat coronaviruses belonging to Sarbecovirus sub-genus. Multiple sequence alignment (MSA) revealed the insertion of four amino acid residues "PRRA" (Proline-Arginine-Arginine-Alanine) to the S1/S2 site in the spike protein of SARS-CoV-2, and structural modeling of spike protein of bat-CoV-RaTG13 also shows a high number of mutations at one of the receptor binding domains (RBD). Acquisition of the furin cleavage sites ("PRRA") along with high number of mutations at one of its RBD is probably responsible for the adaptation of SARS-CoV-2 into human systems. Furthermore, the codon adaptation index (CAI) was used to quantify the magnitude of adaptive efficacy of SARS-CoV-2 in human host in comparison with SARS-CoV. The CAI result showed a relatively less adaptive efficacy of the newly emerged SARS-CoV-2 to the human systems, which might be an indication of its mild clinical severity and progression compared to SARS-CoVs.