Understanding genomic diversity, pan-genome, and evolution of SARS-CoV-2

Parlikar, Arohi; Kalia, Kishan; Sinha, Shruti; Patnaik, Sucheta; Sharma, Neeraj; Vemuri, Sai Gayatri; Sharma, Gaurav

Coronovirus disease 2019 (COVID-19) infection, which originated from Wuhan, China, has seized the whole world in its grasp and created a huge pandemic situation before humanity. Since December 2019, genomes of numerous isolates have been sequenced and analyzed for testing confirmation, epidemiology, and evolutionary studies. In the first half of this article, we provide a detailed review of the history and origin of COVID-19, followed by the taxonomy, nomenclature and genome organization of its causative agent Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2). In the latter half, we analyze subgenus Sarbecovirus (167 SARS-CoV-2, 312 SARS-CoV, and 5 Pangolin CoV) genomes to understand their diversity, origin, and evolution, along with pan-genome analysis of genus Betacoronavirus members. Whole-genome sequence-based phylogeny of subgenus Sarbecovirus genomes reasserted the fact that SARS-CoV-2 strains evolved from their common ancestors putatively residing in bat or pangolin hosts. We predicted a few country-specific patterns of relatedness and identified mutational hotspots with high, medium and low probability based on genome alignment of 167 SARS-CoV-2 strains. A total of 100-nucleotide segment-based homology studies revealed that the majority of the SARS-CoV-2 genome segments are close to Bat CoV, followed by some to Pangolin CoV, and some are unique ones. Open pan-genome of genus Betacoronavirus members indicates the diversity contributed by the novel viruses emerging in this group. Overall, the exploration of the diversity of these isolates, mutational hotspots and pan-genome will shed light on the evolution and pathogenicity of SARS-CoV-2 and help in developing putative methods of diagnosis and treatment.