ArticleeLife2019
The distribution of fitness effects among synonymous mutations in a gene under directional selection.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 144 citations in OpenAlex.
- N-terminal fusion length: The key to reliable and context-preserving regulatory sequence characterization.Synthetic and systems biotechnology · 2027Article
- Synthetic Approaches as Empirical Tools for Testing Evolutionary Theory.Genome biology and evolution · 2026Review
- Synonymous mutations in essential genes infrequently produce fitness effects in human cell lines.Nucleic acids research · 2026Article
- Synonymous variants in IRX4 and their association with congenital heart disease: an in-silico functional assessment.Molecular biology reports · 2026Article
- Mutational basis of ceftazidime-borrelidin A collateral sensitivity in Escherichia coli.G3 (Bethesda, Md.) · 2026Article
- Prime editor-based high-throughput screening reveals functional synonymous mutations in human cells.Nature biotechnology · 2026Article
- Hurdles to horizontal gene transfer: species-specific effects of synonymous variation and plasmid copy number determine antibiotic resistance phenotype.Microbiology (Reading, England) · 2026Article
- Severity of effect considerations regarding the use of mutation as a toxicological endpoint for risk assessment: A report from the 8th International Workshop on Genotoxicity Testing (IWGT).Environmental and molecular mutagenesis · 2025Review
- Functional synonymous mutations and their evolutionary consequences.Nature reviews. Genetics · 2025Review
- Contrasting mutation patterns in haploid and diploid cells from two yeast species.bioRxiv : the preprint server for biology · 2025Article
- Quantifying the intra- and inter-species community interactions in microbiomes by dynamic covariance mapping.Nature communications · 2025Article
- Quantifying the Evolution of SNPs That Affect RNA Secondary Structure in Arabidopsis thaliana Genes.Molecular biology and evolution · 2025Article
- Heat Stress Response inEcology and evolution · 2025Article
- Article
- Integrating next-generation sequencing and artificial intelligence for the identification and validation of pathogenic variants in colorectal cancer.Frontiers in oncology · 2025Article
- Further Evidence for Strong Nonneutrality of Yeast Synonymous Mutations.Molecular biology and evolution · 2024Article
- Synonymous codon substitutions modulate transcription and translation of a divergent upstream gene by modulating antisense RNA production.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- NeMu: a comprehensive pipeline for accurate reconstruction of neutral mutation spectra from evolutionary data.Nucleic acids research · 2024Article
- Unpredictability of the Fitness Effects of Antimicrobial Resistance Mutations Across Environments in Escherichia coli.Molecular biology and evolution · 2024Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The fitness effects of synonymous mutations, nucleotide changes that do not alter the encoded amino acid, have often been assumed to be neutral, but a growing body of evidence suggests otherwise. We used site-directed mutagenesis coupled with direct measures of competitive fitness to estimate the distribution of fitness effects among synonymous mutations for a gene under directional selection and capable of adapting via synonymous nucleotide changes. Synonymous mutations had highly variable fitness effects, both deleterious and beneficial, resembling those of nonsynonymous mutations in the same gene. This variation in fitness was underlain by changes in transcription linked to the creation of internal promoter sites. A positive correlation between fitness and the presence of synonymous substitutions across a phylogeny of related Pseudomonads suggests these mutations may be common in nature. Taken together, our results provide the most compelling evidence to date that synonymous mutations with non-neutral fitness effects may in fact be commonplace.
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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.