Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Bayesian Molecular Dating Analyses Combined with Mutational Profiling Suggest an Independent Origin and Evolution of SARS-CoV-2 Omicron BA.1 and BA.2 Sub-lineages

Naveen Kumar
* ORCID logo ,
Rahul Kaushik
ORCID logo ,
Ashutosh Singh
,
Vladimir N. Uversky
ORCID logo ,
Kam Y. J. Zhang
ORCID logo ,
Upasana Sahu
,
Sandeep Bhatia
,
Aniket Sanyal
Version 1 : Received: 25 October 2022 / Approved: 26 October 2022 / Online: 26 October 2022 (08:15:25 CEST)

A peer-reviewed article of this Preprint also exists.

Kumar, N.; Kaushik, R.; Singh, A.; Uversky, V.N.; Zhang, K.Y.J.; Sahu, U.; Bhatia, S.; Sanyal, A. Bayesian Molecular Dating Analyses Combined with Mutational Profiling Suggest an Independent Origin and Evolution of SARS-CoV-2 Omicron BA.1 and BA.2 Sub-Lineages. Viruses 2022, 14, 2764. Kumar, N.; Kaushik, R.; Singh, A.; Uversky, V.N.; Zhang, K.Y.J.; Sahu, U.; Bhatia, S.; Sanyal, A. Bayesian Molecular Dating Analyses Combined with Mutational Profiling Suggest an Independent Origin and Evolution of SARS-CoV-2 Omicron BA.1 and BA.2 Sub-Lineages. Viruses 2022, 14, 2764.

Abstract

The ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has resulted in the recent emergence of a highly divergent variant of concern (VOC) defined as Omicron or B.1.1.529. This VOC is of particular concern because it has the potential to evade most therapeutic antibodies and has undergone a sustained genetic evolution, resulting in the emergence of five distinct sub-lineages. However, the evolutionary dynamics of initially identified Omicron BA.1 and BA.2 sub-lineages remain poorly understood. Herein, we combined Bayesian phylogenetic analysis, mutational profiling, and selection pressure analysis to track virus genetic changes that drive the early evolutionary dynamics of the Omicron. Based on the Omicron dataset chosen for the improved temporal signals and sampled globally between November 2021 and January 2022, most recent common ancestor (tMRCA) and substitution rates for BA.1 were estimated to be 18 September 2021 (95% highest posterior density (HPD) 04 August – 22 October 2021) and 1.435×10-3 (95% HPD = 1.021×10-3 – 1.869×10-3) substitution/site/year, respectively, whereas 03 November 2021 (95% highest posterior density (HPD) 26 September – 28 November 2021) and 1.074×10-3 (95% HPD = 6.444×10-4 – 1.586×10-3) substitution/site/year for BA.2 sub-lineage. The findings of this study suggest that the Omicron BA.1 and BA.2 sub-lineages originated independently and evolved over time. Furthermore, we identified multiple sites in spike protein undergoing continued diversifying selection that may alter the neutralization profile of BA.1. This study shed light on the ongoing global genomic surveillance and Bayesian molecular dating analyses to better understand the evolutionary dynamics the virus and, as a result, mitigate the impact of emerging variants on public health.

Keywords

COVID-19; SARS-CoV-2 Omicron; tMRCA; evolutionary rate; mutational profiling; selection pressure

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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