Evolutionary shift from purifying selection towards divergent selection of SARS-CoV2 favors its invasion into multiple human organs

Maiti, Amit K

doi:10.1016/j.virusres.2022.198712

Cited by 7 publications

(8 citation statements)

References 68 publications

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“…First, we calculated the proportion of synonymous (pS) and nonsynonymous SBSs (pN) by dividing the count of pS and pN by the count of synonymous and nonsynonymous sites, respectively, for each open reading frame. Next, we estimated the count of synonymous (dS) and nonsynonymous (dN) substitutions per site using the Nei and Gojobori method shown in Equations 1 and 2 [ 38 , 39 ]. Null values of the dN/dS ratio, such as when zero nonsynonymous substitutions in an open reading frame were observed in a given SARS-CoV-2 genomic sequence, were excluded from the analyses.…”

Section: Methodsmentioning

confidence: 99%

Mutational Patterns Observed in SARS-CoV-2 Genomes Sampled From Successive Epochs Delimited by Major Public Health Events in Ontario, Canada: Genomic Surveillance Study

Chen¹,

Randhawa²,

Soltysiak³

et al. 2022

JMIR Bioinform Biotech

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Background The emergence of SARS-CoV-2 variants with mutations associated with increased transmissibility and virulence is a public health concern in Ontario, Canada. Characterizing how the mutational patterns of the SARS-CoV-2 genome have changed over time can shed light on the driving factors, including selection for increased fitness and host immune response, that may contribute to the emergence of novel variants. Moreover, the study of SARS-CoV-2 in the microcosm of Ontario, Canada can reveal how different province-specific public health policies over time may be associated with observed mutational patterns as a model system. Objective This study aimed to perform a comprehensive analysis of single base substitution (SBS) types, counts, and genomic locations observed in SARS-CoV-2 genomic sequences sampled in Ontario, Canada. Comparisons of mutational patterns were conducted between sequences sampled during 4 different epochs delimited by major public health events to track the evolution of the SARS-CoV-2 mutational landscape over 2 years. Methods In total, 24,244 SARS-CoV-2 genomic sequences and associated metadata sampled in Ontario, Canada from January 1, 2020, to December 31, 2021, were retrieved from the Global Initiative on Sharing All Influenza Data database. Sequences were assigned to 4 epochs delimited by major public health events based on the sampling date. SBSs from each SARS-CoV-2 sequence were identified relative to the MN996528.1 reference genome. Catalogues of SBS types and counts were generated to estimate the impact of selection in each open reading frame, and identify mutation clusters. The estimation of mutational fitness over time was performed using the Augur pipeline. Results The biases in SBS types and proportions observed support previous reports of host antiviral defense activity involving the SARS-CoV-2 genome. There was an increase in U>C substitutions associated with adenosine deaminase acting on RNA (ADAR) activity uniquely observed during Epoch 4. The burden of novel SBSs observed in SARS-CoV-2 genomic sequences was the greatest in Epoch 2 (median 5), followed by Epoch 3 (median 4). Clusters of SBSs were observed in the spike protein open reading frame, ORF1a, and ORF3a. The high proportion of nonsynonymous SBSs and increasing dN/dS metric (ratio of nonsynonymous to synonymous mutations in a given open reading frame) to above 1 in Epoch 4 indicate positive selection of the spike protein open reading frame. Conclusions Quantitative analysis of the mutational patterns of the SARS-CoV-2 genome in the microcosm of Ontario, Canada within early consecutive epochs of the pandemic tracked the mutational dynamics in the context of public health events that instigate significant shifts in selection and mutagenesis. Continued genomic surveillance of emergent variants will be useful for the design of public health policies in response to the evolving COVID-19 pandemic.

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Section: Methodsmentioning

confidence: 99%

Mutational Patterns Observed in SARS-CoV-2 Genomes Sampled From Successive Epochs Delimited by Major Public Health Events in Ontario, Canada: Genomic Surveillance Study

Chen¹,

Randhawa²,

Soltysiak³

et al. 2022

JMIR Bioinform Biotech

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“…ω-Alpha-Sept20 Despite the estimation of the mutation rate of SARS-CoV-2 (9 × 10 −4 /site/year) [7,8], the rate of nonsynonymous over synonymous mutation, which actually impacts the viral functions, has not been estimated earlier. I estimated that the instant rate of change in the ω (dω/dt) at any given time is 0.03/month (1.2 × 10 −5 /site/year) and the strain-specific average rate of change in the ω is 0.025/month (1.00 × 10 −5 /site/year) (Figure 2c, Supplementary Table S2).…”

Section: Gene Namementioning

confidence: 99%

“…A virus undergoes divergent selection when novel conditions are created, due to environmental changes over a short period or a heterogeneous environment with multiple niches [ 6 ]. SARS-CoV-2 has a substitution rate of 2.22 nt/month with an evolutionary rate of 9 × 10 −4 /site/year [ 7 , 8 ]. SARS-CoV-2 evolution from bat RaTG13 strictly follows neutral evolution with strong purifying selection, whereas its propagation in the human proceeds towards divergent selection due to its ability to infect multiple human organs that act as constrained environments because of variations in immune surveillance [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…SARS-CoV-2 has a substitution rate of 2.22 nt/month with an evolutionary rate of 9 × 10 −4 /site/year [ 7 , 8 ]. SARS-CoV-2 evolution from bat RaTG13 strictly follows neutral evolution with strong purifying selection, whereas its propagation in the human proceeds towards divergent selection due to its ability to infect multiple human organs that act as constrained environments because of variations in immune surveillance [ 7 ]. This property enables SARS-CoV-2 to select more nonsynonymous mutations to survive aggressively, and to become virulent.…”

Section: Introductionmentioning

confidence: 99%

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Progressive Evolutionary Dynamics of Gene-Specific ω Led to the Emergence of Novel SARS-CoV-2 Strains Having Super-Infectivity and Virulence with Vaccine Neutralization

Maiti

2024

IJMS

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An estimation of the proportion of nonsynonymous to synonymous mutation (dn/ds, ω) of the SARS-CoV-2 genome would indicate the evolutionary dynamics necessary to evolve into novel strains with increased infection, virulence, and vaccine neutralization. A temporal estimation of ω of the whole genome, and all twenty-nine SARS-CoV-2 genes of major virulent strains of alpha, delta and omicron demonstrates that the SARS-CoV-2 genome originally emerged (ω ~ 0.04) with a strong purifying selection (ω < 1) and reached (ω ~ 0.85) in omicron towards diversifying selection (ω > 1). A marked increase in the ω occurred in the spike gene from alpha (ω = 0.2) to omicron (ω = 1.97). The ω of the replication machinery genes including RDRP, NSP3, NSP4, NSP7, NSP8, NSP10, NSP13, NSP14, and ORF9 are markedly increased, indicating that these genes/proteins are yet to be evolutionary stabilized and are contributing to the evolution of novel virulent strains. The delta-specific maximum increase in ω in the immunomodulatory genes of NSP8, NSP10, NSP16, ORF4, ORF5, ORF6, ORF7A, and ORF8 compared to alpha or omicron indicates delta-specific vulnerabilities for severe COVID-19 related hospitalization and death. The maximum values of ω are observed for spike (S), NSP4, ORF8 and NSP15, which indicates that the gene-specific temporal estimation of ω identifies specific genes for its super-infectivity and virulency that could be targeted for drug development.

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“…Since sgRNAs are only transcribed in infected cells, they serve as indicators of active replication [ 11 ] and their reduced expression has been associated with mild COVID-19 cases [ 12 ]. The most common changes in SARS-CoV-2 are single nucleotide substitutions (SNSs), although insertions and deletions have also been reported [ 13 , 14 ]. Single nucleotide variants (SNVs) are found in various sites on non-structural genes that code for 16 nsp on the first 2/3 of the SARS genome as well on structural proteins as S, which is responsible for recognition of the host receptor protein [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of SARS-CoV-2 ORF7a Deletions from COVID-19-Positive Individuals and Its Impact on Virus Spread in Cell Culture

Simas

Costa

Gomes

et al. 2023

Viruses

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The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the COVID-19 outbreak, posed a primary concern of public health worldwide. The most common changes in SARS-CoV-2 are single nucleotide substitutions, also reported insertions and deletions. This work investigates the presence of SARS-CoV-2 ORF7a deletions identified in COVID-19-positive individuals. Sequencing of SARS-CoV-2 complete genomes showed three different ORF7a size deletions (190-nt, 339-nt and 365-nt). Deletions were confirmed through Sanger sequencing. The ORF7a∆190 was detected in a group of five relatives with mild symptoms of COVID-19, and the ORF7a∆339 and ORF7a∆365 in a couple of co-workers. These deletions did not affect subgenomic RNAs (sgRNA) production downstream of ORF7a. Still, fragments associated with sgRNA of genes upstream of ORF7a showed a decrease in size when corresponding to samples with deletions. In silico analysis suggests that the deletions impair protein proper function; however, isolated viruses with partial deletion of ORF7a can replicate in culture cells similarly to wild-type viruses at 24 hpi, but with less infectious particles after 48 hpi. These findings on deleted ORF7a accessory protein gene, contribute to understanding SARS-CoV-2 phenotypes such as replication, immune evasion and evolutionary fitness as well insights into the role of SARS-CoV-2_ORF7a in the mechanism of virus-host interactions.

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Evolutionary shift from purifying selection towards divergent selection of SARS-CoV2 favors its invasion into multiple human organs

Cited by 7 publications

References 68 publications

Mutational Patterns Observed in SARS-CoV-2 Genomes Sampled From Successive Epochs Delimited by Major Public Health Events in Ontario, Canada: Genomic Surveillance Study

Mutational Patterns Observed in SARS-CoV-2 Genomes Sampled From Successive Epochs Delimited by Major Public Health Events in Ontario, Canada: Genomic Surveillance Study

Progressive Evolutionary Dynamics of Gene-Specific ω Led to the Emergence of Novel SARS-CoV-2 Strains Having Super-Infectivity and Virulence with Vaccine Neutralization

Evaluation of SARS-CoV-2 ORF7a Deletions from COVID-19-Positive Individuals and Its Impact on Virus Spread in Cell Culture

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