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

Abstract

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.

A unique view of SARS-CoV-2 through the lens of ORF8 protein

“…In the later stages of the SARS-CoV epidemic it was found that a 29 nucleotide deletion in the ORF8 protein caused it to split into ORF8a (39 aa) and ORF8b (84aa) rendering it functionless while the SARS-CoV-2 ORF8 is intact [19]. Also, the SARS-CoV ORF8 had a function in interspecies transmission and viral replication efficiency as a reported 382 nucleotide deletion, which included ORF8ab resulted in a reduced ability of viral replication in human cells [20]. However, the SARS-CoV-2 ORF8 mainly acts as an immune-modulator by down-regulating MHC class I molecules, therefore protecting the infected cells against cytotoxic T cell killing of target cells.…”

A unique view of SARS-CoV-2 through the lens of ORF8 protein

“…Each of the ORF8 amino acid sequences (96 variants) was aligned concerning the ORF8 protein (YP 009724396.1) from Wuhan, China, using the multiple sequence alignment tools (NCBI Blastp suite), and the corresponding results were used to identify mutations and their associated positions [ 47 ]. It is noted that a mutation from an amino acid A1 to A2 at a position p is denoted by A1pA2 or A1(p)A2.…”

“…Patients with the Δ382 variant exhibited less severe symptoms, including milder hypoxic conditions and low cytokine activity compared to patients infected with the wildtype virus [ 26 ]. Also, the SARS-CoV-2 ORF8 functions in interspecies transmission and viral replication efficiency as the Δ382 deletion variant resulted in a reduced viral replication ability in human cells [ 27 ]. However, the SARS-CoV-2 ORF8 mainly acts as an immune-modulator by down-regulating MHC class I molecules, thereby shielding the infected cells against cytotoxic T cell, killing the target cells ( Fig.…”

Different SARS-CoV-2 haplotypes associate with geographic origin and case fatality rates of COVID-19 patients

“…Host variation is usually associated with pathogen adaptation and evolution. The relevance of viral variation in this respect has been studied by Parlikar et al (2020) who analyzed 167 SARS-CoV-2, 312 SARS-CoV, and 5 Pangolin CoV genomes to help understand their origin and evolution. The phylogeny of the subgenus Sarbecovirus confirmed the fact that SARS-CoV-2 strains evolved from their common ancestors putatively residing in bat or pangolin hosts.…”