ArticleBiology direct2007
Neutral genetic drift can alter promiscuous protein functions, potentially aiding functional evolution.
Article in Biology direct, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
- Impact of genome duplication on secondary metabolite composition in non-cultivated species: a systematic meta-analysis.Annals of botany · 2020Pooled it
- Promiscuity-Guided Enzyme Evolution via Substrate Multiplexed Screening.Angewandte Chemie (International ed. in English) · 2026Review
- 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
- Neutral drift upon threshold-like selection promotes variation in antibiotic resistance phenotype.Nature communications · 2024Article
- Development of a high throughput cytochrome P450 ligand-binding assay.The Journal of biological chemistry · 2024Article
- Analysis of neutral mutational drift in an allosteric enzyme.Protein science : a publication of the Protein Society · 2023Article
- Ultrahigh-Throughput Enzyme Engineering and Discovery inChemical reviews · 2023Review
- Robustness and innovation in synthetic genotype networks.Nature communications · 2023Article
- A snapshot on HIV-1 evolution through the identification of phylogenetic-specific properties of HIV-1 integrases M/O.PLoS pathogens · 2023Article
- Dan Tawfik's Lessons for Protein Engineers about Enzymes Adapting to New Substrates.Biochemistry · 2023Review
- Intragenic compensation through the lens of deep mutational scanning.Biophysical reviews · 2022Review
- Droplet-based screening of phosphate transfer catalysis reveals how epistasis shapes MAP kinase interactions with substrates.Nature communications · 2022Article
- Climbing Up and Down Binding Landscapes through Deep Mutational Scanning of Three Homologous Protein-Protein Complexes.Journal of the American Chemical Society · 2021Article
- Ancestral sequence reconstruction - An underused approach to understand the evolution of gene function in plants?Computational and structural biotechnology journal · 2021Review
- An Overview of Antennal Esterases in Lepidoptera.Frontiers in physiology · 2021Review
- Scalable continuous evolution for the generation of diverse enzyme variants encompassing promiscuous activities.Nature communications · 2020Article
- An allosteric pathway explains beneficial fitness in yeast for long-range mutations in an essential TIM barrel enzyme.Protein science : a publication of the Protein Society · 2020Article
- Quantitative mapping of binding specificity landscapes for homologous targets by using a high-throughput method.The Biochemical journal · 2020Article
- A Continuing Career in Biocatalysis: Frances H. Arnold.ACS catalysis · 2019Article
19 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
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMany of the mutations accumulated by naturally evolving proteins are neutral in the sense that they do not significantly alter a protein's ability to perform its primary biological function. However, new protein functions evolve when selection begins to favor other, "promiscuous" functions that are incidental to a protein's original biological role. If mutations that are neutral with respect to a protein's primary biological function cause substantial changes in promiscuous functions, these mutations could enable future functional evolution.
resultsHere we investigate this possibility experimentally by examining how cytochrome P450 enzymes that have evolved neutrally with respect to activity on a single substrate have changed in their abilities to catalyze reactions on five other substrates. We find that the enzymes have sometimes changed as much as four-fold in the promiscuous activities. The changes in promiscuous activities tend to increase with the number of mutations, and can be largely rationalized in terms of the chemical structures of the substrates. The activities on chemically similar substrates tend to change in a coordinated fashion, potentially providing a route for systematically predicting the change in one activity based on the measurement of several others.
conclusionOur work suggests that initially neutral genetic drift can lead to substantial changes in protein functions that are not currently under selection, in effect poising the proteins to more readily undergo functional evolution should selection favor new functions in the future.
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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.