Preprint Article Version 3 Preserved in Portico This version is not peer-reviewed

Trends of Mutation Accumulation Across Global SARS-CoV-2 Genomes: Implications for the Evolution of the Novel Coronavirus

Version 1 : Received: 27 May 2020 / Approved: 28 May 2020 / Online: 28 May 2020 (16:21:05 CEST)
Version 2 : Received: 28 July 2020 / Approved: 30 July 2020 / Online: 30 July 2020 (06:22:00 CEST)
Version 3 : Received: 3 October 2020 / Approved: 5 October 2020 / Online: 5 October 2020 (10:56:36 CEST)

How to cite: Roy, C.; Mandal, S.M.; Mondol, S.K.; Mukherjee, S.; Ghosh, W.; Chakraborty, R. Trends of Mutation Accumulation Across Global SARS-CoV-2 Genomes: Implications for the Evolution of the Novel Coronavirus. Preprints 2020, 2020050463 (doi: 10.20944/preprints202005.0463.v3). Roy, C.; Mandal, S.M.; Mondol, S.K.; Mukherjee, S.; Ghosh, W.; Chakraborty, R. Trends of Mutation Accumulation Across Global SARS-CoV-2 Genomes: Implications for the Evolution of the Novel Coronavirus. Preprints 2020, 2020050463 (doi: 10.20944/preprints202005.0463.v3).

Abstract

To understand SARS-CoV-2 microevolution, this study explored the genome-wide frequency, gene-wise distribution, and molecular nature of all point-mutations detected across its 71,703 RNA-genomes deposited in the GISAID repository, till 21 August 2020. Globally, nsp1/nsp2/nsp3/ nsp11 and orf7a/orf3a/S were the most mutation-ridden non-structural and structural genes respectively. Phylogeny based on 4,618 spatiotemporally-representative genomes revealed that entities belonging to the early lineages are mostly spread over Asian countries (including India, the biggest hotspot of the pandemic) whereas the recently-derived lineages are more globally distributed. Of the total 16,602 polymorphism-bearing sites in the pan-genome, 11,037 and 4,965 involved transitions and transversions, which in turn were predominated by cytidine-to-uridine and guanosine-to-uridine conversions, respectively. Positive selection of nonsynonymous mutations (dN/dS >1) in most of the structural, but not non-structural, genes indicated that SARS-CoV-2 has already harmonized its replication/transcription machineries with the host’s metabolic system, while it is still redefining virulence/transmissibility strategies at the molecular level.

Subject Areas

SARS-CoV-2; genome-wide mutations; transition; transversion; nonsynonymous and synonymous mutations; microevolution

Comments (1)

Comment 1
Received: 5 October 2020
Commenter: Ranadhir Chakraborty
Commenter's Conflict of Interests: Author
Comment: SARS-CoV-2 microevolution was studied alongside the global trends of point-mutation in a universal dataset of 71,703 genomes. Globally, nsp1/nsp2/nsp3/ nsp11 and orf7a/orf3a/S were the most mutation-ridden non-structural and structural genes respectively. Whole-genome phylogeny revealed that entities belonging to the early lineages are mostly spread over Asian countries (including India) whereas the recently-derived lineages are more globally distributed. A transition:transversion ratio of 2.22 characterized the nucleotide substitution bias of SARS-CoV-2, with cytidine-to-uridine and guanosine-to-uridine conversions being the predominant transition and transversion types respectively. Nonsynonymous mutations are under positive selection in most of the structural, but not non-structural, genes.
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