ArticleProceedings of the National Academy of Sciences of the United States of America2008
A compromise required by gene sharing enables survival: Implications for evolution of new enzyme activities.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 89 citations in OpenAlex.
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- Intramolecular epistasis correlates with divergence of specificity in promiscuous and bifunctional NSAR/OSBS enzymes.Protein science : a publication of the Protein Society · 2025Article
- Frustration can Limit the Adaptation of Promiscuous Enzymes Through Gene Duplication and Specialisation.Journal of molecular evolution · 2024Article
- Cell Survival Enabled by Leakage of a Labile Metabolic Intermediate.Molecular biology and evolution · 2023Article
- How to Recruit a Promiscuous Enzyme to Serve a New Function.Biochemistry · 2023Article
- Substrate Dynamics Contribute to Enzymatic Specificity in Human and Bacterial Methionine Adenosyltransferases.JACS Au · 2021Article
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- Experimental Evolution of Innovation and Novelty.Trends in ecology & evolution · 2019Review
- Multifaceted Stoichiometry Control of Bacterial Operons Revealed by Deep Proteome Quantification.Frontiers in genetics · 2019Article
- Metabolic repair through emergence of new pathways in Escherichia coli.Nature chemical biology · 2018Article
- Synonymous mutations make dramatic contributions to fitness when growth is limited by a weak-link enzyme.PLoS genetics · 2018Article
- Evolutionary repurposing of a sulfatase: A new Michaelis complex leads to efficient transition state charge offset.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
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- A Synonymous Mutation Upstream of the Gene Encoding a Weak-Link Enzyme Causes an Ultrasensitive Response in Growth Rate.Journal of bacteriology · 2016Article
- Functional Trade-Offs in Promiscuous Enzymes Cannot Be Explained by Intrinsic Mutational Robustness of the Native Activity.PLoS genetics · 2016Article
- Crystal Structure of the LysY·LysW Complex from Thermus thermophilus.The Journal of biological chemistry · 2016Article
- Evidence that Environmental Heterogeneity Maintains a Detoxifying Enzyme Polymorphism in Drosophila melanogaster.Current biology : CB · 2016Article
- Rapid bursts and slow declines: on the possible evolutionary trajectories of enzymes.Journal of the Royal Society, Interface · 2015Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Evolution of new enzymatic activities is believed to require a period of gene sharing in which a single enzyme must serve both its original function and a new function that has become advantageous to the organism. Subsequent gene duplication allows one copy to maintain the original function, while the other diverges to optimize the new function. The physiological impact of gene sharing and the constraints imposed by the need to maintain the original activity during the early stages of evolution of a new activity have not been addressed experimentally. We report here an investigation of the evolution of a new activity under circumstances in which both the original and the new activity are critical for growth. Glutamylphosphate reductase (ProA) has a very low promiscuous activity with N-acetylglutamylphosphate, the normal substrate for ArgC (N-acetylglutamylphosphate reductase). A mutation that changes Glu-383 to Ala increases the promiscuous activity by 12-fold but decreases the original activity by 2,800-fold. The impairment in Pro and Arg synthesis results in 14-fold overexpression of E383A ProA, providing sufficient N-acetylglutamylphosphate reductase activity to allow a strain lacking ArgC to grow on glucose. Thus, reaching the threshold level of NAGP reductase activity required for survival required both a structural mutation and overexpression of the enzyme. Notably, overexpression does not require a mutation in the regulatory region of the protein; amino acid limitation attributable to the poor catalytic abilities of E383A ProA causes a physiological response that results in overexpression.
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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.