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

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: NSP, non-structural protein; SARS-CoV-2, COVID-19, genome-wide, evolution, variants, VOC, VOI, VUM, SNP, mutation, non-synonymous, silent mutation, spike, RNA dependent RNA polymerase, NSP, UTR: Abbreviations: VOC, variant of concern; UTR, untranslated region; VOI, variant of interest; VUM, variant under monitoring; rdrp, RNA dependent RNA polymerase.

Fig. 1

Maximum likelihood whole genome-based phylogeny of SARS-CoV-2 VOCs, VOIs and VUMs. Here, phylogroups (PG-I and PG-II) and clades (alpha, beta, gamma, delta, omicron, mu etc.) are marked with respective colors as indicated. Bootstrap values are represented by the radius of circle at the nodes. Common ancestry of omicron and lambda is marked by black star.

Fig. 2

Mutational analysis of omicron. Six panel image displays the most mutated samples, overall mutations per samples, most frequent events per class of mutation category, changes of nucleotide per type, nucleotide wise most frequent events and protein level most frequent events for the genomes used in the study.

Fig. 3

Mutational analysis of omicron (A) Number of mutations in the coding region is in the centre of the pie-chart representing indels (black), synonymous (yellow) and non-synonymous (red) SNPs. Type and number of mutations in the extergenic region is represented by pie charts blue, light blue and white as represented in the color legends. (B) Bar graph representing number of mutations in the genomic region of SARS-CoV-2. (C) Some of the top mutations (pl. refer Table 3 for all top mutations in omicron) among the omicron variant are represented by stars of black: indels, yellow: synonymous and red: non-synonymous mutations.