ArticleProceedings of the National Academy of Sciences of the United States of America2009
Potential role of phenotypic mutations in the evolution of protein expression and stability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49 citing papers in PubMed.
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- NMR measurements of transient low-populated tautomeric and anionic Watson-Crick-like G·T/U in RNA:DNA hybrids: implications for the fidelity of transcription and CRISPR/Cas9 gene editing.Nucleic acids research · 2024Article
- Fitness Effects of Phenotypic Mutations at Proteome-Scale Reveal Optimality of Translation Machinery.Molecular biology and evolution · 2024Article
- Phenotypic mutations contribute to protein diversity and shape protein evolution.Protein science : a publication of the Protein Society · 2022Review
- Mechanisms of protein evolution.Protein science : a publication of the Protein Society · 2022Review
- Mistranslation Reduces Mutation Load in Evolving Proteins through Negative Epistasis with DNA Mutations.Molecular biology and evolution · 2021Article
- Article
- The Relationship between the Misfolding Avoidance Hypothesis and Protein Evolutionary Rates in the Light of Empirical Evidence.Genome biology and evolution · 2021Article
- The Boggarts of biology: how non-genetic changes influence the genotype.Current genetics · 2021Review
- Protein Structural Information and Evolutionary Landscape by In Vitro Evolution.Molecular biology and evolution · 2020Article
- Structures of hyperstable ancestral haloalkane dehalogenases show restricted conformational dynamics.Computational and structural biotechnology journal · 2020Article
- What drives phenotypic divergence among coral clonemates of Acropora palmata?Molecular ecology · 2019Article
- Population Genetics Based Phylogenetics Under Stabilizing Selection for an Optimal Amino Acid Sequence: A Nested Modeling Approach.Molecular biology and evolution · 2019Article
- The causes of evolvability and their evolution.Nature reviews. Genetics · 2019Review
- Robustness by intrinsically disordered C-termini and translational readthrough.Nucleic acids research · 2018Article
- Identification of Novel Neisseria gonorrhoeae Lineages Harboring Resistance Plasmids in Coastal Kenya.The Journal of infectious diseases · 2018Article
- Review
- Conformational dynamics and enzyme evolution.Journal of the Royal Society, Interface · 2018Review
- Characterization of Reconstructed Ancestral Proteins Suggests a Change in Temperature of the Ancient Biosphere.Life (Basel, Switzerland) · 2017Review
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2 authors.
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Abstract
Phenotypic mutations (errors occurring during protein synthesis) are orders of magnitude more frequent than genetic mutations. Consequently, the sequences of individual protein molecules transcribed and translated from the same gene can differ. To test the effects of such mutations, we established a bacterial system in which an antibiotic resistance gene (TEM-1 beta-lactamase) was transcribed by either a high-fidelity RNA polymerase or its error-prone mutant. This setup enabled the analysis of individual mRNA transcripts that were synthesized under normal or error-prone conditions. We found that an increase of approximately 20-fold in the frequency of transcription errors promoted the evolution of higher TEM-1 expression levels and of more stable enzyme variants. The stabilized variants exhibited a distinct advantage under error-prone transcription, although under normal transcription they conferred resistance similar to wild-type TEM-1. They did so, primarily, by increasing TEM-1's tolerance to destabilizing deleterious mutations that arise from transcriptional errors. The stabilized TEM-1 variants also showed increased tolerance to genetic mutations. Thus, although phenotypic mutations are not individually subjected to inheritance and natural selection, as are genetic mutations, they collectively exert a direct and immediate effect on protein fitness. They may therefore play a role in shaping protein traits such as expression levels, stability, and tolerance to genetic mutations.
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