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

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.

Impacto del COVID-19 en la circulación de virus respiratorios en un hospital pediátrico: una ausencia esperada

“…Las variantes que, por azar, tengan algunas ventajas adaptativas pueden implantarse, propagarse y, en ocasiones, convertirse en la versión predominante del SARS-CoV-2, en un proceso de selección natural. 29 En cuanto a las medidas de prevención, el estrecho contacto social aumenta el riesgo de transmisión desde un individuo infectado a otros susceptibles. En consecuencia, mantener las medidas de distanciamiento, el uso de tapabocas y la higiene de manos demostraron ser medidas suficientes y eficaces para disminuir la propagación no solo del SARS-CoV-2, sino también de los restantes virus respiratorios.…”

Full vaccination against COVID-19 suppresses SARS-CoV-2 delta variant and spike gene mutation frequencies and generates purifying selection pressure

“…Ln is the nucleotide length of the genome/locus. Ns is the number of sequenced entities present in the dataset (Roy et al, 2020). The information of fully vaccinated rate on 3 July 2021 in individual counties were obtained in Our World in Data (https://ourworldindata.org/covid-vaccinations).…”

“…Mutations drive genome variability, generating many different SARS-CoV-2 variants as the virus evolves to escape vaccine-mediated immunity and thereby, develop drug or vaccine resistance (Roy et al, 2020). The delta (lineage B1.617.2) variants were first documented in October 2020 in India and were designated variants of concern by the World Health Organization in May of 2021 due to its increased transmissibility and virulence (https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/).…”

“…The delta (lineage B1.617.2) variants were first documented in October 2020 in India and were designated variants of concern by the World Health Organization in May of 2021 due to its increased transmissibility and virulence (https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/). All SARS-CoV-2 mutations result from two major mechanisms: (1) spontaneous substitution/deletion of nucleotides, and (2) RNA recombination (Roy et al, 2020, Yeh and Contreras, 2020, Ignatieva et al, 2021, Yeh and Contreras, 2021.…”

Rapid longitudinal SARS-CoV-2 intra-host emergence of novel haplotypes regardless of immune deficiencies

“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to spread world-wide, with over 5 million of deaths out of more than 250 million of positive cases reported since the beginning of the pandemic (1). There is extensive evidence that SARS-CoV-2 genome has evolved and has acquired several mutations conferring higher viral fitness, with almost all genomic sites being affected by mutation events (2–4).…”