ArticleNucleic acids research2012
Evolutionary transitions to new DNA methyltransferases through target site expansion and shrinkage.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Expanding the landscape of BREX diversity: uncovering multi-layered functional frameworks and identification of novel BREX-related defense systems.Nucleic acids research · 2026Article
- Conversion of the CG specific M.MpeI DNA methyltransferase into an enzyme predominantly methylating CCA and CCC sites.Nucleic acids research · 2024Article
- Dan Tawfik's Lessons for Protein Engineers about Enzymes Adapting to New Substrates.Biochemistry · 2023Review
- Engineering the protein dynamics of an ancestral luciferase.Nature communications · 2021Article
- Mutational Pathways and Trade-Offs Between HisA and TrpF Functions: Implications for Evolution via Gene Duplication and Divergence.Frontiers in microbiology · 2020Article
- Isospecific adenine DNA methyltransferases show distinct preferences towards DNA substrates.Scientific reports · 2018Article
- Editorial: Evolution acting on the same target, but at multiple levels: Proteins as the test case.Journal of biosciences · 2017Article
- Functional Trade-Offs in Promiscuous Enzymes Cannot Be Explained by Intrinsic Mutational Robustness of the Native Activity.PLoS genetics · 2016Article
- An Ancient Fingerprint Indicates the Common Ancestry of Rossmann-Fold Enzymes Utilizing Different Ribose-Based Cofactors.PLoS biology · 2016Article
- Systematic Mapping of Protein Mutational Space by Prolonged Drift Reveals the Deleterious Effects of Seemingly Neutral Mutations.PLoS computational biology · 2015Article
- Specificity of the ModA11, ModA12 and ModD1 epigenetic regulator N(6)-adenine DNA methyltransferases of Neisseria meningitidis.Nucleic acids research · 2015Article
- Enzyme promiscuity: engine of evolutionary innovation.The Journal of biological chemistry · 2014Review
- Evolution of DNA specificity in a transcription factor family produced a new gene regulatory module.Cell · 2014Article
- Article
- Increasing cleavage specificity and activity of restriction endonuclease KpnI.Nucleic acids research · 2013Article
- Correlated occurrence and bypass of frame-shifting insertion-deletions (InDels) to give functional proteins.PLoS genetics · 2013Article
- Fidelity index determination of DNA methyltransferases.PloS one · 2013Article
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2 authors.
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No grant is acknowledged in the PubMed record.
Abstract
DNA-binding and modifying proteins show high specificity but also exhibit a certain level of promiscuity. Such latent promiscuous activities comprise the starting points for new protein functions, but this hypothesis presents a paradox: a new activity can only evolve if it already exists. How then, do novel activities evolve? DNA methyltransferases, for example, are highly divergent in their target sites, but how transitions toward novel sites occur remains unknown. We performed laboratory evolution of the DNA methyltransferase M.HaeIII. We found that new target sites emerged primarily through expansion of the original site, GGCC, and the subsequent shrinkage of evolved expanded sites. Variants evolved for sites that are promiscuously methylated by M.HaeIII [GG((A)/(T))CC and GGCGCC] carried mutations in 'gate-keeper' residues. They could thereby methylate novel target sites such as GCGC and GGATCC that were neither selected for nor present in M.HaeIII. These 'generalist' intermediates were further evolved to obtain variants with novel target specificities. Our results demonstrate the ease by which new DNA-binding and modifying specificities evolve and the mechanism by which they occur at both the protein and DNA levels.
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