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Virology Journal
Published in: Virology Journal 1/2023

Open Access 01-12-2023 | SARS-CoV-2 | Research

Genome analysis of SARS-CoV-2 isolates from a population reveals the rapid selective sweep of a haplotype carrying many pre-existing and new mutations

Authors: Maloyjo Joyraj Bhattacharjee, Anupam Bhattacharya, Bhaswati Kashyap, Manash Jyoti Taw, Wen-Hsiung Li, Ashis K. Mukherjee, Mojibur Rohman Khan

Published in: Virology Journal | Issue 1/2023

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Abstract

To understand the mechanism underlying the evolution of SARS-CoV-2 in a population, we sequenced 92 viral genomes from Assam, India. Analysis of these and database sequences revealed a complete selective sweep of a haplotype in Assam carrying 13 pre-existing variants, including a high leap in frequency of a variant on ORF8, which is involved in immune evasion. A comparative study between sequences of same lineage and similar time frames in and outside Assam showed that 10 of the 13 pre-existing variants had a frequency ranging from 96 to 99%, and the remaining 3 had a low frequency outside Assam. Using a phylogenetic approach to infer sequential occurrences of variants we found that the variant Phe120del on ORF8, which had a low frequency (1.75%) outside Assam, is at the base of the phylogenetic tree of variants and became totally fixed (100%) in Assam population. Based on this observation, we inferred that the variant on ORF8 had a selective advantage, so it carried the haplotype to reach the100% frequency. The haplotype also carried 32 pre-existing variants at a frequency from 1.00 to 80.00% outside Assam. Those of these variants that are more closely linked to the S-protein locus, which often carries advantageous mutations and is tightly linked to the ORF8 locus, retained higher frequencies, while the less tightly linked variants showed lower frequencies, likely due to recombination among co- circulating variants in Assam. The ratios of non-synonymous substitutions to synonymous substitutions suggested that some genes such as those coding for the S-protein and non-structural proteins underwent positive selection while others were subject to purifying selection during their evolution in Assam. Furthermore, we observed negative correlation of the Ct value of qRT-PCR of the patients with abundant ORF6 transcripts, suggesting that ORF6 can be used as a marker for estimating viral titer. In conclusion, our in-depth analysis of SARS-CoV-2 genomes in a regional population reveals the mechanism and dynamics of viral evolution.
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Metadata
Title
Genome analysis of SARS-CoV-2 isolates from a population reveals the rapid selective sweep of a haplotype carrying many pre-existing and new mutations
Authors
Maloyjo Joyraj Bhattacharjee
Anupam Bhattacharya
Bhaswati Kashyap
Manash Jyoti Taw
Wen-Hsiung Li
Ashis K. Mukherjee
Mojibur Rohman Khan
Publication date
01-12-2023
Publisher
BioMed Central
Keyword
SARS-CoV-2
Published in
Virology Journal / Issue 1/2023
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-023-02139-3

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