ArticleHFSP journal2007
Latent evolutionary potentials under the neutral mutational drift of an enzyme.
Article in HFSP journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed.
- How far can you go? Extrapolating values of catalytic activity from known protein landscapes in natural and directed evolution.Chemical Society reviews · 2026Review
- Sequence-based generative AI design of versatile tryptophan synthases.Nature communications · 2026Article
- Active site diversification of a non-canonical amino acid decarboxylase by merging substrate multiplexed screening with computationally guided recombination.Protein science : a publication of the Protein Society · 2025Article
- Tracing the stepwise Darwinian evolution of a plant halogenase.Science advances · 2025Article
- Neutral drift upon threshold-like selection promotes variation in antibiotic resistance phenotype.Nature communications · 2024Article
- Deciphering the liquid-liquid phase separation induced modulation in the structure, dynamics, and enzymatic activity of an ordered protein β-lactoglobulin.Chemical science · 2024Article
- Analysing a Group of Homologous BAHD Enzymes Provides Insights into the Evolutionary Transition of Rosmarinic Acid Synthases from Hydroxycinnamoyl-CoA:Shikimate/Quinate Hydroxycinnamoyl Transferases.Plants (Basel, Switzerland) · 2024Article
- Ultrahigh-Throughput Enzyme Engineering and Discovery inChemical reviews · 2023Review
- Dan Tawfik's Lessons for Protein Engineers about Enzymes Adapting to New Substrates.Biochemistry · 2023Review
- Paracatalytic induction: Subverting specificity in hedgehog protein autoprocessing with small molecules.Methods in enzymology · 2023Article
- Mechanisms of protein evolution.Protein science : a publication of the Protein Society · 2022Review
- Dynamic RNA Fitness Landscapes of a Group I Ribozyme during Changes to the Experimental Environment.Molecular biology and evolution · 2022Article
- GCAT: A network model of mutational influences between amino acid positions in PSD95Frontiers in molecular biosciences · 2022Article
- Promiscuous Ribozymes and Their Proposed Role in Prebiotic Evolution.Chemical reviews · 2020Review
- Organophosphorus Nerve Agents: Types, Toxicity, and Treatments.Journal of toxicology · 2020Review
- Genotype network intersections promote evolutionary innovation.PLoS biology · 2019Article
- Probing pathways of adaptation with continuous evolution.Current opinion in systems biology · 2019Article
- Article
- Towards a Stochastic Paradigm: From Fuzzy Ensembles to Cellular Functions.Molecules (Basel, Switzerland) · 2018Article
- A highly stable laccase obtained by swapping the second cupredoxin domain.Scientific reports · 2018Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Biological systems exhibit mutational robustness, or neutrality, whereby the impact of mutations is minimized. Does neutrality hamper their ability to adapt in the face of changing environments? We monitored changes in genotype and phenotype that occur within a neutral mutational network of an enzyme, experimentally and computationally (see accompanying article). Using the enzyme PON1 as a model, we performed random mutagenesis and purifying selection to purge deleterious mutations. We characterized approximately 300 variants that are apparently neutral, or close to neutral, with respect to PON1's levels of expression and native lactonase activity. Their activities with promiscuous substrates and ligands indicated significant changes in adaptive potentials. Almost half of the variants exhibited changes in promiscuous activities, specificities, or inhibition, and several of these were found to be one or two mutations, closer to potentially new phenotypes: aryl esterase, thiolactonase, phosphotriesterase, or drug resistance. This empirical measure of phenotypic changes under neutrality supports the notion that sequence changes that are neutral, i.e., non-adaptive, in a current context can facilitate adaptation under changing circumstances, by both expanding the activity range of existing enzymes and thus providing an immediate advantage, and by reducing the number of mutations required for divergence of new functions.
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Registered trials
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