ArticleMolecular biology and evolution2016
Compensating the Fitness Costs of Synonymous Mutations.
Article in Molecular biology and evolution, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 48 citations in OpenAlex.
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- Improving the generalization of protein expression models with mechanistic sequence information.Nucleic acids research · 2025Article
- Fitness benefits of a synonymous substitution in an ancient EF-Tu gene depend on the genetic background.Journal of bacteriology · 2024Article
- Not Quite Lost in Translation: Mistranslation Alters Adaptive Landscape Topography and the Dynamics of Evolution.Molecular biology and evolution · 2023Article
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- Detection by metagenomic functional analysis and improvement by experimental evolution of β-lactams resistance genes present in oil contaminated soils.Scientific reports · 2022Article
- The cost of evolved constitutiveEcology and evolution · 2021Article
- Reconstructing the Evolutionary History of a Highly Conserved Operon Cluster in Gammaproteobacteria and Bacilli.Genome biology and evolution · 2021Article
- Spurious regulatory connections dictate the expression-fitness landscape of translation factors.Molecular systems biology · 2021Article
- ΦX174 Attenuation by Whole-Genome Codon Deoptimization.Genome biology and evolution · 2021Article
- Genome-Based Analyses of Fitness Effects and Compensatory Changes Associated with Acquisition ofAntibiotics (Basel, Switzerland) · 2021Article
- Population Bottlenecks Strongly Influence the Evolutionary Trajectory to Fluoroquinolone Resistance in Escherichia coli.Molecular biology and evolution · 2020Article
- Synonymous Mutations inFrontiers in microbiology · 2020Article
- Synonymous genome recoding: a tool to explore microbial biology and new therapeutic strategies.Nucleic acids research · 2019Review
- Repeated Phenotypic Evolution by Different Genetic Routes in Pseudomonas fluorescens SBW25.Molecular biology and evolution · 2019Article
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- Codon usage influences fitness through RNA toxicity.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The Codon Usage of Lowly Expressed Genes Is Subject to Natural Selection.Genome biology and evolution · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synonymous mutations do not change the sequence of the polypeptide but they may still influence fitness. We investigated in Salmonella enterica how four synonymous mutations in the rpsT gene (encoding ribosomal protein S20) reduce fitness (i.e., growth rate) and the mechanisms by which this cost can be genetically compensated. The reduced growth rates of the synonymous mutants were correlated with reduced levels of the rpsT transcript and S20 protein. In an adaptive evolution experiment, these fitness impairments could be compensated by mutations that either caused up-regulation of S20 through increased gene dosage (due to duplications), increased transcription of the rpsT gene (due to an rpoD mutation or mutations in rpsT), or increased translation from the rpsT transcript (due to rpsT mutations). We suggest that the reduced levels of S20 in the synonymous mutants result in production of a defective subpopulation of 30S subunits lacking S20 that reduce protein synthesis and bacterial growth and that the compensatory mutations restore S20 levels and the number of functional ribosomes. Our results demonstrate how specific synonymous mutations can cause substantial fitness reductions and that many different types of intra- and extragenic compensatory mutations can efficiently restore fitness. Furthermore, this study highlights that also synonymous sites can be under strong selection, which may have implications for the use of dN/dS ratios as signature for selection.
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