ArticleMolecular biology and evolution2024
Further Evidence for Strong Nonneutrality of Yeast Synonymous Mutations.
Article in Molecular biology and evolution, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
8 citing papers in PubMed.
- Genomic constraint and hypervariability correlate with fitness effects in elite tetraploid potato breeding material.PLoS genetics · 2026Article
- Synonymous mutations in essential genes infrequently produce fitness effects in human cell lines.Nucleic acids research · 2026Article
- A naturally synonymous mutation modulates an ERK-centered regulatory network to mediate thermotolerance divergence in Crassostrea oysters.Communications biology · 2026Article
- CDsyn: A comprehensive database for deleterious human synonymous variation prediction.iScience · 2026Article
- TPdsm: a method based on TabPFN for prediction of deleterious synonymous mutations.Bioinformatics advances · 2026Article
- Adaptive tracking with antagonistic pleiotropy results in seemingly neutral molecular evolution.Nature ecology & evolution · 2025Article
- Functional synonymous mutations and their evolutionary consequences.Nature reviews. Genetics · 2025Review
- Substitution-Mutation Rate Ratio (c/µ) As Molecular Adaptation Test Beyond Ka/Ks: A SARS-COV-2 Case Study.Journal of molecular evolution · 2025Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Although synonymous mutations are commonly assumed neutral or nearly so, recent years have seen reports of fitness effects of synonymous mutations detected under laboratory conditions. In a previous study, we used genome editing to construct thousands of yeast mutants each carrying a synonymous or nonsynonymous mutation in one of 21 genes, and discovered that most synonymous and most nonsynonymous mutations are deleterious. A concern was raised that this observation could be caused by the fitness effects of potential CRISPR/Cas9 off-target edits and/or secondary mutations, and an experiment that would be refractory to such effects was proposed. Using genome sequencing, we here show that no CRISPR/Cas9 off-target editing occurred, although some mutants did carry secondary mutations. Analysis of mutants with negligible effects from secondary mutations and new data collected from the proposed experiment confirms the original conclusion. These findings, along with other reports of fitness effects of synonymous mutations from both case and systematic studies, necessitate a paradigm shift from assuming (near) neutrality of synonymous mutations.
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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 Socratic graph.