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

• We are witnessing arms race between evolution of SARS-CoV-2 and research community for timely management of its detection and therapeutic regime. • Comprehensive genome dynamics study of omicron variant with the previously reported variants (VOC, VOI and VUM) suggests its mutational cascade. • Phylogenomics suggests a shared ancestry between omicron and lambda variant. • 18,261 mutations were detected among 302 high-quality genomes of omicron variant majority of which were non-synonymous in the coding region. • Non-synonymous mutations were skewed towards spike (∼60%) (A67, T547K, D614G, H655Y, N679K, P681H, D796Y, N856K, Q954H), RNA dependent RNA polymerase (∼20%) (A1892T, I189V, P314L, K38R, T492I, V57V) and ∼5% in nucleocapsid (RG203KR). Emergence of new variant of SARS-CoV-2, namely omicron, has posed a global concern because of its high rate of transmissibility and mutations in its genome. Researchers worldwide are trying to understand the evolution and emergence of such variants to understand the mutational cascade events. We have considered all omicron genomes (n = 302 genomes) available till 2nd December 2021 in the public repository of GISAID along with representatives of variants of concern (VOC), i.e., alpha, beta, gamma, delta, and omicron; variant of interest (VOI) mu and lambda; and variant under monitoring (VUM). Whole genome-based phylogeny and mutational analysis were performed to understand the evolution of SARS CoV-2 leading to emergence of omicron variant. Whole genome-based phylogeny depicted two phylogroups (PG-I and PG-II) forming variant specific clades except for gamma and VUM GH. Mutational analysis detected 18,261 mutations in the omicron variant, majority of which were non-synonymous mutations in spike (A67, T547K, D614G, H655Y, N679K, P681H, D796Y, N856K, Q954H), followed by RNA dependent RNA polymerase (rdrp) (A1892T, I189V, P314L, K38R, T492I, V57V), ORF6 (M19M) and nucleocapsid protein (RG203KR). Delta and omicron have evolutionary diverged into distinct phylogroups and do not share a common ancestry. While, omicron shares common ancestry with VOI lambda and its evolution is mainly derived by the non-synonymous mutations. [ABSTRACT FROM AUTHOR]