Natural selection pressure exerted on “Silent” mutations during the evolution of SARS-CoV-2: Evidence from codon usage and RNA structure

Bai, Haoxiang; Ata, Galal; Sun, Qing; Rahman, Siddiq Ur; Tao, Shiheng

doi:10.1016/j.virusres.2022.198966

Cited by 8 publications

(3 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most recently, a 2023 paper by Bai et al describes a limited characterization of the influence of synonymous mutations on potential RNA structure; contrary to our findings, that work reports a dN/dS ratio of less than 1, indicating purifying selection, and observes a roughly even distribution of synonymous mutations throughout the genome [3]. In this work, the authors analyze 6483 viral genomes in terms of their synonymous and non-synonymous mutation occurences as compared to the reference genome for the purposes of assessing codon usage changes over time.…”

Section: Discussioncontrasting

confidence: 99%

Structural impact of synonymous mutations in six SARS-CoV-2 Variants of Concern

Ziesel,

Jabbari

2024

Preprint

View full text Add to dashboard Cite

SARS-CoV-2 continues to spread and infect people worldwide. While most effort into characterizing variants of this virus have focused on non-synonymous changes, accumulation of synonymous mutations in different viral variants has also occurred. Here we characterize six Variants of Concern in terms of their mutational content, and make predictions regarding the impact of those mutations on potential genomic RNA secondary structure and stability. We find that synonymous mutations typically have no or modest impact to RNA secondary structure. As synonymous mutations are free from the selective pressure imposed on protein-altering mutations, the impact of synonymous mutations is largely limited to RNA secondary structure considerations. The absence of major, structure-altering synonymous mutations emphasize the importance of RNA structure, including within coding regions, to viral fitness.

show abstract

Section: Discussioncontrasting

confidence: 99%

Structural impact of synonymous mutations in six SARS-CoV-2 Variants of Concern

Ziesel,

Jabbari

2024

Preprint

View full text Add to dashboard Cite

show abstract

“…d N /d S ratio analysis : As d N /d S ratios exceed unity for each SARS-CoV-2 variant, positive selection is responsible for promoting d N in the sequences. From Table 6 , the average genomic d N /d S of all SARS-CoV-2 variants is estimated to be around 0.86 compared to the Wuhan reference strain which is similar with another study that estimated it to be 0.8446 ( 104 ). Also, it was observed that Delta variant had the highest d N /d S ratio (1.43) showing positive selection, followed by Omicron variant (1.01) showing neutral selection.…”

Section: Resultssupporting

confidence: 84%

Analysis of SARS-CoV-2 genome evolutionary patterns

Gupta,

Bhatnagar

2024

Microbiol Spectr

View full text Add to dashboard Cite

The spread of SARS-CoV-2 virus accompanied by public availability of abundant sequence data provides a window for the determination of viral evolutionary patterns. In this study, SARS-CoV-2 genome sequences were collected from seven countries in the period January 2020–December 2022. The sequences were classified into three phases, namely, pre-vaccination, post-vaccination, and recent period. Comparison was performed between these phases based on parameters like mutation rates, selection pressure (d N /d S ratio), and transition to transversion ratios (T i /T v ). Similar comparisons were performed among SARS-CoV-2 variants. Statistical significance was tested using Graphpad unpaired t -test. The analysis showed an increase in the percent genomic mutation rates post-vaccination and in recent periods across all countries from the pre-vaccination sequences. Mutation rates were highest in NSP3, S, N, and NSP12b before and increased further after vaccination. NSP4 showed the largest change in mutation rates after vaccination. The d N /d S ratios showed purifying selection that shifted toward neutral selection after vaccination. N, ORF8, ORF3a, and ORF10 were under highest positive selection before vaccination. Shift toward neutral selection was driven by E, NSP3, and ORF7a in the after vaccination set. In recent sequences, the largest d N /d S change was observed in E, NSP1, and NSP13. The T i /T v ratios decreased with time. C→U and G→U were the most frequent transitions and transversions. However, U→G was the most frequent transversion in recent period. The Omicron variant had the highest genomic mutation rates, while Delta showed the highest d N /d S ratio. Protein-wise d N /d S ratio was also seen to vary across the different variants. IMPORTANCE To the best of our knowledge, there exists no other large-scale study of the genomic and protein-wise mutation patterns during the time course of evolution in different countries. Analyzing the SARS-CoV-2 evolutionary patterns in view of the varying spatial, temporal, and biological signals is important for diagnostics, therapeutics, and pharmacovigilance of SARS-CoV-2.

show abstract

“…This is to be expected because synonymous mutations have fewer restrictions and do not alter the coded protein. However, codon usage and the maintenance of the RNA secondary structure are two forces that can cause some selection pressure on synonymous mutations [47]. The distribution of synonymous mutations and mutations from UTRs are comparable (Figure S7).…”

Section: Most Frequent Snvsmentioning

confidence: 99%

The Mutational Landscape of SARS-CoV-2

Saldivar-Espinoza,

Garcia-Segura,

Novau-Ferré

et al. 2023

IJMS

View full text Add to dashboard Cite

Mutation research is crucial for detecting and treating SARS-CoV-2 and developing vaccines. Using over 5,300,000 sequences from SARS-CoV-2 genomes and custom Python programs, we analyzed the mutational landscape of SARS-CoV-2. Although almost every nucleotide in the SARS-CoV-2 genome has mutated at some time, the substantial differences in the frequency and regularity of mutations warrant further examination. C>U mutations are the most common. They are found in the largest number of variants, pangolin lineages, and countries, which indicates that they are a driving force behind the evolution of SARS-CoV-2. Not all SARS-CoV-2 genes have mutated in the same way. Fewer non-synonymous single nucleotide variations are found in genes that encode proteins with a critical role in virus replication than in genes with ancillary roles. Some genes, such as spike (S) and nucleocapsid (N), show more non-synonymous mutations than others. Although the prevalence of mutations in the target regions of COVID-19 diagnostic RT-qPCR tests is generally low, in some cases, such as for some primers that bind to the N gene, it is significant. Therefore, ongoing monitoring of SARS-CoV-2 mutations is crucial. The SARS-CoV-2 Mutation Portal provides access to a database of SARS-CoV-2 mutations.

show abstract

Natural selection pressure exerted on “Silent” mutations during the evolution of SARS-CoV-2: Evidence from codon usage and RNA structure

Cited by 8 publications

References 56 publications

Structural impact of synonymous mutations in six SARS-CoV-2 Variants of Concern

Structural impact of synonymous mutations in six SARS-CoV-2 Variants of Concern

Analysis of SARS-CoV-2 genome evolutionary patterns

The Mutational Landscape of SARS-CoV-2

Contact Info

Product

Resources

About