ArticleMolecular biology and evolution2022
The Structural Determinants of Intra-Protein Compensatory Substitutions.
Article in Molecular biology and evolution, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 16 citations in OpenAlex.
- Epistasis among clustered lineage-specific amino acid substitutions in the Drosophila Trio protein.PLoS genetics · 2026Article
- Tandem repeats in human brain evolution and disease susceptibility.Molecules and cells · 2026Review
- Predictors of Protein Evolution in the drosophilid Immune System.Genome biology and evolution · 2026Article
- Correlated Evolution Drives Structural Convergence of Interacting Proteins.Journal of molecular evolution · 2026Article
- Detecting Convergence of Amino Acid Physicochemical Properties Underlying the Organismal Adaptive Convergent Evolution.Molecular ecology resources · 2025Article
- Epistasis among clustered lineage-specific adaptive amino acid substitutions in the Drosophila Trio protein.bioRxiv : the preprint server for biology · 2025Article
- How residence time works in allosteric drugs.Current opinion in structural biology · 2025Review
- Language models reveal a complex sequence basis for adaptive convergent evolution of protein functions.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- PHACE: Phylogeny-Aware Detection of Molecular Coevolution.Molecular biology and evolution · 2025Article
- Compensatory Evolution Following Deleterious Episodes of GC-biased Gene Conversion in Rodents.Molecular biology and evolution · 2025Article
- Comparative Analysis of Drosophila Bam and Bgcn Sequences and Predicted Protein Structural Evolution.Journal of molecular evolution · 2025Article
- Selection among site-dependent structurally constrained substitution models of protein evolution by approximate Bayesian computation.Bioinformatics (Oxford, England) · 2024Article
- The Site/Group Extended Data Format and Tools.Genome biology and evolution · 2024Article
- Adaptive evolution and co-evolution of chloroplast genomes in Pteridaceae species occupying different habitats: overlapping residues are always highly mutated.BMC plant biology · 2023Article
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Compensatory substitutions happen when one mutation is advantageously selected because it restores the loss of fitness induced by a previous deleterious mutation. How frequent such mutations occur in evolution and what is the structural and functional context permitting their emergence remain open questions. We built an atlas of intra-protein compensatory substitutions using a phylogenetic approach and a dataset of 1,630 bacterial protein families for which high-quality sequence alignments and experimentally derived protein structures were available. We identified more than 51,000 positions coevolving by the mean of predicted compensatory mutations. Using the evolutionary and structural properties of the analyzed positions, we demonstrate that compensatory mutations are scarce (typically only a few in the protein history) but widespread (the majority of proteins experienced at least one). Typical coevolving residues are evolving slowly, are located in the protein core outside secondary structure motifs, and are more often in contact than expected by chance, even after accounting for their evolutionary rate and solvent exposure. An exception to this general scheme is residues coevolving for charge compensation, which are evolving faster than noncoevolving sites, in contradiction with predictions from simple coevolutionary models, but similar to stem pairs in RNA. While sites with a significant pattern of coevolution by compensatory mutations are rare, the comparative analysis of hundreds of structures ultimately permits a better understanding of the link between the three-dimensional structure of a protein and its fitness landscape.
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