ArticleGenome biology and evolution2012
Estimating the rate of irreversibility in protein evolution.
Article in Genome biology and evolution, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Tandem repeats in human brain evolution and disease susceptibility.Molecules and cells · 2026Review
- Epistatic drift in protein evolution.Current opinion in genetics & development · 2025Review
- Specialization Restricts the Evolutionary Paths Available to Yeast Sugar Transporters.Molecular biology and evolution · 2024Article
- Specialization restricts the evolutionary paths available to yeast sugar transporters.bioRxiv : the preprint server for biology · 2024Article
- Intragenic compensation through the lens of deep mutational scanning.Biophysical reviews · 2022Review
- Phylogenetic inference of changes in amino acid propensities with single-position resolution.PLoS computational biology · 2022Article
- Genomic Features and Evolution of the Parapoxvirus during the Past Two Decades.Pathogens (Basel, Switzerland) · 2020Article
- Senescence and entrenchment in evolution of amino acid sites.Nature communications · 2020Article
- Disadvantages and benefits of evolved unicellularity versus multicellularity in budding yeast.Ecology and evolution · 2019Article
- Compensatory mutations and epistasis for protein function.Current opinion in structural biology · 2018Review
- Pervasive contingency and entrenchment in a billion years of Hsp90 evolution.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Resurrecting ancestral structural dynamics of an antiviral immune receptor: adaptive binding pocket reorganization repeatedly shifts RNA preference.BMC evolutionary biology · 2016Article
- Epistasis in protein evolution.Protein science : a publication of the Protein Society · 2016Review
- Article
- Causes of molecular convergence and parallelism in protein evolution.Nature reviews. Genetics · 2016Review
- Changing preferences: deformation of single position amino acid fitness landscapes and evolution of proteins.Biology letters · 2015Review
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- Massively parallel enzyme kinetics reveals the substrate recognition landscape of the metalloprotease ADAMTS13.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Contingency and entrenchment in protein evolution under purifying selection.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Whether or not evolutionary change is inherently irreversible remains a controversial topic. Some examples of evolutionary irreversibility are known; however, this question has not been comprehensively addressed at the molecular level. Here, we use data from 221 human genes with known pathogenic mutations to estimate the rate of irreversibility in protein evolution. For these genes, we reconstruct ancestral amino acid sequences along the mammalian phylogeny and identify ancestral amino acid states that match known pathogenic mutations. Such cases represent inherent evolutionary irreversibility because, at the present moment, reversals to these ancestral amino acid states are impossible for the human lineage. We estimate that approximately 10% of all amino acid substitutions along the mammalian phylogeny are irreversible, such that a return to the ancestral amino acid state would lead to a pathogenic phenotype. For a subset of 51 genes with high rates of irreversibility, as much as 40% of all amino acid evolution was estimated to be irreversible. Because pathogenic phenotypes do not resemble ancestral phenotypes, the molecular nature of the high rate of irreversibility in proteins is best explained by evolution with a high prevalence of compensatory, epistatic interactions between amino acid sites. Under such mode of protein evolution, once an amino acid substitution is fixed, the probability of its reversal declines as the protein sequence accumulates changes that affect the phenotypic manifestation of the ancestral state. The prevalence of epistasis in evolution indicates that the observed high rate of irreversibility in protein evolution is an inherent property of protein structure and function.
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