ArticleHeredity2018
Unraveling the causes of adaptive benefits of synonymous mutations in TEM-1 β-lactamase.
Article in Heredity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- Synthetic Approaches as Empirical Tools for Testing Evolutionary Theory.Genome biology and evolution · 2026Review
- Synonymous codon-optimized multiplex qPCR for simultaneous detection ofJournal of clinical microbiology · 2026Article
- A noncoding SNP in ELF3 alters ELF3β expression and confers adaptation of Arabidopsis to a continental climate.Plant physiology · 2026Article
- Functional synonymous mutations and their evolutionary consequences.Nature reviews. Genetics · 2025Review
- Effect of Mutations on the Evolution of Extended Spectrum β-lactamases (ESBL).The protein journal · 2025Review
- Global genomic epidemiology ofMicrobial genomics · 2024Article
- Link Between Individual Codon Frequencies and Protein Expression: Going Beyond Codon Adaptation Index.International journal of molecular sciences · 2024Article
- Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria.Nature communications · 2024Article
- Fitness benefits of a synonymous substitution in an ancient EF-Tu gene depend on the genetic background.Journal of bacteriology · 2024Article
- Synonymous edits in theProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Molecular Mechanisms and the Significance of Synonymous Mutations.Biomolecules · 2024Review
- Transcriptome-based strategies for identifying aluminum tolerance genes in popcorn (Zea mays L. var. everta).Scientific reports · 2023Article
- Signatures of kin selection in a natural population of the bacteriaEvolution letters · 2023Article
- Multi-animal-model study reveals mutations in neural plasticity and nociception genes linked to excessive alcohol drinking.Alcohol, clinical & experimental research · 2023Article
- ASCARIS: Positional feature annotation and protein structure-based representation of single amino acid variations.Computational and structural biotechnology journal · 2023Article
- The High Mutational Sensitivity of ccdA Antitoxin Is Linked to Codon Optimality.Molecular biology and evolution · 2022Article
- Omicron variant (B.1.1.529) and its sublineages: What do we know so far amid the emergence of recombinant variants of SARS-CoV-2?Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- On the incongruence of genotype-phenotype and fitness landscapes.PLoS computational biology · 2022Article
- GroEL/S Overexpression Helps to Purge Deleterious Mutations and Reduce Genetic Diversity during Adaptive Protein Evolution.Molecular biology and evolution · 2022Article
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Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While synonymous mutations were long thought to be without phenotypic consequences, there is growing evidence they can affect gene expression, protein folding, and ultimately the fitness of an organism. In only a few cases have the mechanisms by which synonymous mutations affect the phenotype been elucidated. We previously identified 48 mutations in TEM-1 β-lactamase that increased resistance of Escherichia coli to cefotaxime, 10 of which were synonymous. To better understand the molecular mechanisms underlying the beneficial effect of these synonymous mutations, we made a series of measurements for a panel containing the 10 synonymous together with 10 non-synonymous mutations as a reference. Whereas messenger levels were unaffected, we found that total and functional TEM protein levels were higher for 5 out of 10 synonymous mutations. These observations suggest that some of these mutations act on translation or a downstream process. Similar effects were observed for some small-benefit non-synonymous mutations, suggesting a similar causal mechanism. For the synonymous mutations, we found that the cost of resistance scales with TEM protein levels. A resistance landscape for four synonymous mutations revealed strong epistasis: none of the combinations of mutations exceeded the resistance of the largest-effect mutation and there were synthetically neutral combinations. By considering combined effects of these mutations, we could infer that functional TEM protein level is a multi-dimensional phenotype. These results suggest that synonymous mutations may have beneficial effects by increasing the expression of an enzyme with low substrate activity, which may be realized via multiple, yet unknown, post-transcriptional mechanisms.
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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.