ArticleBiochemistry2013
A population-based experimental model for protein evolution: effects of mutation rate and selection stringency on evolutionary outcomes.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Programmable gene insertion in human cells with a laboratory-evolved CRISPR-associated transposase.Science (New York, N.Y.) · 2025Article
- Recent advances on protein engineering for improved stability.Biodesign research · 2025Review
- Effects of selection stringency on the outcomes of directed evolution.bioRxiv : the preprint server for biology · 2024Article
- Continuous evolution of compact protein degradation tags regulated by selective molecular glues.Science (New York, N.Y.) · 2024Article
- Article
- Methods for the directed evolution of biomolecular interactions.Trends in biochemical sciences · 2022Review
- Systematic molecular evolution enables robust biomolecule discovery.Nature methods · 2022Article
- Phage-assisted continuous and non-continuous evolution.Nature protocols · 2020Article
- Making 3D-Cry Toxin Mutants: Much More Than a Tool of Understanding Toxins Mechanism of Action.Toxins · 2020Review
- Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity.Nature biotechnology · 2020Article
- Using Cellular Automata to Simulate Domain Evolution in Proteins.Frontiers in genetics · 2020Article
- Continuous evolution of base editors with expanded target compatibility and improved activity.Nature biotechnology · 2019Article
- Probing pathways of adaptation with continuous evolution.Current opinion in systems biology · 2019Article
- Darwin Assembly: fast, efficient, multi-site bespoke mutagenesis.Nucleic acids research · 2018Article
- Continuous directed evolution of aminoacyl-tRNA synthetases.Nature chemical biology · 2017Article
- Evolution of a split RNA polymerase as a versatile biosensor platform.Nature chemical biology · 2017Article
- Article
- A Panel of Protease-Responsive RNA Polymerases Respond to Biochemical Signals by Production of Defined RNA Outputs in Live Cells.Journal of the American Chemical Society · 2015Article
- Development of potent in vivo mutagenesis plasmids with broad mutational spectra.Nature communications · 2015Article
- Synthetic biology for the directed evolution of protein biocatalysts: navigating sequence space intelligently.Chemical Society reviews · 2015Review
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6 authors.
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Abstract
Protein evolution is a critical component of organismal evolution and a valuable method for the generation of useful molecules in the laboratory. Few studies, however, have experimentally characterized how fundamental parameters influence protein evolution outcomes over long evolutionary trajectories or multiple replicates. In this work, we applied phage-assisted continuous evolution (PACE) as an experimental platform to study evolving protein populations over hundreds of rounds of evolution. We varied evolutionary conditions as T7 RNA polymerase evolved to recognize the T3 promoter DNA sequence and characterized how specific combinations of both mutation rate and selection stringency reproducibly result in different evolutionary outcomes. We observed significant and dramatic increases in the activity of the evolved RNA polymerase variants on the desired target promoter after selection for 96 h, confirming positive selection occurred under all conditions. We used high-throughput sequencing to quantitatively define convergent genetic solutions, including mutational "signatures" and nonsignature mutations that map to specific regions of protein sequence. These findings illuminate key determinants of evolutionary outcomes, inform the design of future protein evolution experiments, and demonstrate the value of PACE as a method for studying protein evolution.
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