The rapid emergence of multiple sublineages of Omicron (B.1.1.529) variant: Dynamic profiling via molecular phylogenetics and mutational landscape studies

Abstract

Purpose: The recent Omicron (B.1.1.529) variant poses a significant threat to global health. This variant has spread worldwide, and several sublineages have rapidly emerged. Study tried to analyze the microevolution of this variant. Methods: We studied the molecular phylogenetics, divergence, geographical distributions, frequencies, risk mutations for antibody affinity, and mutational landscape for Omicron sublineages using in silico analysis and statistical models. The risk mutation of spike for nAb affinity was analyzed and illustrated by statistical plots. Finally, the mutational properties of the spike mutations and their stability were predicted and demonstrated. Results: First, we studied the microevolutionary Omicron sublineages using molecular phylogenetics. Simultaneously, we revealed divergence events of the Omicron sublineages and observed the lowest minimum divergence of 51 in clade 21K and the highest maximum divergence of 90 in clade 21L. We have demonstrated cluster analyses, geographical distributions, frequencies of Omicron and its sublineages. Finally, we evaluated the mutational landscape of the Omicron sublineages. In this mutational study, we performed a genome-wide analysis of general mutations, mutations in the non-spike genome, and spike mutations of Omicron sublineages. The risk mutation of S-glycoprotein for nAb affinity has been analyzed for Omicron sublineages. Here, we found that some sublineages have all four significant highly destabilizing mutations. Such sublineages are BA.1 (G446S, E484A, T95I, and D614G), BA.2 (H655Y, Q493R, G493S, and D614G), BA.4 (N501Y, Y505H, N969K, and D614G), and BA.2.75 (Q454H, T547K, N764K, D614G and G446S). Finally, from the mutation stability prediction through ΔΔG, we observed that BA.1 and BA.4 had two destabilizing and two stabilizing mutations. Similarly, BA.2, BA.5, and BA.2.12.1 have one destabilizing and three stabilizing mutations. However, all four mutations in BA.2.75 are stabilizing mutations. Conclusions: Our molecular phylogenetic studies provided a deeper understanding of the microevolution of sublineages and the creation of Omicron. Similarly, this study might help scientists develop pan-coronavirus vaccines that consider their mutational properties.

Keywords

• Sublineages of Omicron
• Molecular phylogenetics
• Divergence
• Mutational landscape
• Risk mutation