ArticleMolecular biology and evolution2021
Evidence for Strong Mutation Bias toward, and Selection against, U Content in SARS-CoV-2: Implications for Vaccine Design.
Article in Molecular biology and evolution, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 56 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Time Series Analysis of SARS-CoV-2 Genomes and Correlations among Highly Prevalent Mutations.Microbiology spectrum · 2022Pooled it
- Coronaviruses reprogram the tRNA epitranscriptome to favor viral protein expression.Nature communications · 2026Article
- Article
- Functional Genomic Evidence for Candidate Small Viral RNA-Mediated Epigenetic Interference in SARS-CoV-1 and SARS-CoV-2.Computational and structural biotechnology journal · 2026Article
- Bacterial gene 5' ends have unusual mutation rates that can mislead tests of selection.PLoS biology · 2025Article
- C > U mutations generate immunogenic peptides in SARS-CoV-2.Nature communications · 2025Article
- Convergent Evolution and Host-Limiting Impacts of SARS-CoV-2 Revealed by Cellular Experiments.Molecular biology and evolution · 2025Article
- The mutational landscape of SARS-CoV-2 provides new insight into viral evolution and fitness.Nature communications · 2025Article
- An Expanding Universe of Mutational Signatures and Its Rapid Evolution in Single-Stranded RNA Viruses.Molecular biology and evolution · 2025Article
- Enhanced Antitumor Immunity Through T Cell Activation with Optimized Tandem Double-OX40L mRNAs.International journal of nanomedicine · 2025Article
- SARS-CoV-2 and innate immunity: the good, the bad, and the "goldilocks".Cellular & molecular immunology · 2024Review
- Trends and impacts of SARS-CoV-2 genome sharing: a comparative analysis of China and the global community, 2020-2023.Frontiers in public health · 2024Article
- An elusive debate on the evidence for RNA editing in SARS-CoV-2.RNA biology · 2024Article
- Mutation bias and adaptation in bacteria.Microbiology (Reading, England) · 2023Review
- Recent Advances and Innovations in the Preparation and Purification of In Vitro-Transcribed-mRNA-Based Molecules.Pharmaceutics · 2023Review
- Optimization and Deoptimization of Codons in SARS-CoV-2 and Related Implications for Vaccine Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Review
- Article
- Mutation bias and the predictability of evolution.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Correlated substitutions reveal SARS-like coronaviruses recombine frequently with a diverse set of structured gene pools.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Large-scale re-engineering of synonymous sites is a promising strategy to generate vaccines either through synthesis of attenuated viruses or via codon-optimized genes in DNA vaccines. Attenuation typically relies on deoptimization of codon pairs and maximization of CpG dinucleotide frequencies. So as to formulate evolutionarily informed attenuation strategies that aim to force nucleotide usage against the direction favored by selection, here, we examine available whole-genome sequences of SARS-CoV-2 to infer patterns of mutation and selection on synonymous sites. Analysis of mutational profiles indicates a strong mutation bias toward U. In turn, analysis of observed synonymous site composition implicates selection against U. Accounting for dinucleotide effects reinforces this conclusion, observed UU content being a quarter of that expected under neutrality. Possible mechanisms of selection against U mutations include selection for higher expression, for high mRNA stability or lower immunogenicity of viral genes. Consistent with gene-specific selection against CpG dinucleotides, we observe systematic differences of CpG content between SARS-CoV-2 genes. We propose an evolutionarily informed approach to attenuation that, unusually, seeks to increase usage of the already most common synonymous codons. Comparable analysis of H1N1 and Ebola finds that GC3 deviated from neutral equilibrium is not a universal feature, cautioning against generalization of results.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.