ArticleNature communications2022
Deciphering polymorphism in 61,157 Escherichia coli genomes via epistatic sequence landscapes.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 20 citations in OpenAlex.
- Epistasis and co-adaptation in bacterial genome evolution.Nature reviews. Genetics · 2026Review
- Origins and breadth of pairwise epistasis in an α-helix of β-lactamase TEM-1.Nature communications · 2026Article
- DEX: a consensus-based amino acid exchangeability measure for improved codon substitution modelling.bioRxiv : the preprint server for biology · 2026Article
- Functional bottlenecks can emerge from non-epistatic underlying traits.PLoS computational biology · 2026Article
- Inferring context-specific site variation with evotuned protein language models.NAR genomics and bioinformatics · 2026Article
- Estimating the proportion of beneficial mutations that are not adaptive in mammals.PLoS genetics · 2024Article
- Emergent time scales of epistasis in protein evolution.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Understanding epistatic networks in the B1 β-lactamases through coevolutionary statistical modeling and deep mutational scanning.Nature communications · 2024Article
- Machine learning in biological physics: From biomolecular prediction to design.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The physical and evolutionary energy landscapes of devolved protein sequences corresponding to pseudogenes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- In vivo functional phenotypes from a computational epistatic model of evolution.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Predicting the effect of mutations to investigate recent events of selection across 60,472Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Deciphering polymorphism in 61,157 Escherichia coli genomes via epistatic sequence landscapes.Nature communications · 2022Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Characterizing the effect of mutations is key to understand the evolution of protein sequences and to separate neutral amino-acid changes from deleterious ones. Epistatic interactions between residues can lead to a context dependence of mutation effects. Context dependence constrains the amino-acid changes that can contribute to polymorphism in the short term, and the ones that can accumulate between species in the long term. We use computational approaches to accurately predict the polymorphisms segregating in a panel of 61,157 Escherichia coli genomes from the analysis of distant homologues. By comparing a context-aware Direct-Coupling Analysis modelling to a non-epistatic approach, we show that the genetic context strongly constrains the tolerable amino acids in 30% to 50% of amino-acid sites. The study of more distant species suggests the gradual build-up of genetic context over long evolutionary timescales by the accumulation of small epistatic contributions.
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