ReviewCurrent opinion in genetics & development2013
Should evolutionary geneticists worry about higher-order epistasis?
Review in Current opinion in genetics & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
183 citing papers in PubMed, 327 citations in OpenAlex.
- Deconstructing empirical fitness seascapes across scales of granularity.G3 (Bethesda, Md.) · 2026Article
- Epistasis: Just say no!The Journal of biological chemistry · 2026Review
- Additive effects of environmental and demographic variation shape the repeatability of evolution across replicated experiments.Evolution letters · 2026Article
- How far can you go? Extrapolating values of catalytic activity from known protein landscapes in natural and directed evolution.Chemical Society reviews · 2026Review
- Maynard Smith's analogy, realized: Common ancestry constrains evolutionary percolation through protein space.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Growth of fatty acid vesicles coupled with amino acid sequences of peptides toward evolvable protocells.Communications chemistry · 2026Article
- Determinants of metal import and specificity in a bacterial transporter.bioRxiv : the preprint server for biology · 2026Article
- Competition's Role in Shaping Cryptic Genetic Variation.Evolution & development · 2026Article
- Functional bottlenecks can emerge from non-epistatic underlying traits.PLoS computational biology · 2026Article
- Deconstructing empirical fitness seascapes across scales of granularity.bioRxiv : the preprint server for biology · 2026Article
- Inference and Visualization of Complex Genotype-Phenotype Maps.Molecular biology and evolution · 2026Article
- Sign Epistasis Can be Absent in Multi-peaked Landscapes With Neutral Mutations.Genome biology and evolution · 2026Article
- Evolutionary cell biology comes of age.Journal of cell science · 2025Article
- Epistatic drift in protein evolution.Current opinion in genetics & development · 2025Review
- Environment-by-Environment Interactions Differ Across Genetic Backgrounds.Molecular biology and evolution · 2025Article
- Inference and visualization of complex genotype-phenotype maps withbioRxiv : the preprint server for biology · 2025Article
- Learning sequence-function relationships with scalable, interpretable Gaussian processes.bioRxiv : the preprint server for biology · 2025Article
- EarlybioRxiv : the preprint server for biology · 2025Article
- Longitudinal sequencing reveals polygenic and epistatic nature of genomic response to selection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Importance of higher-order epistasis in protein sequence-function relationships.bioRxiv : the preprint server for biology · 2025Article
123 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Natural selection drives evolving populations up the fitness landscape, the projection from nucleotide sequence space to organismal reproductive success. While it has long been appreciated that topographic complexities on fitness landscapes can arise only as a consequence of epistatic interactions between mutations, evolutionary genetics has mainly focused on epistasis between pairs of mutations. Here we propose a generalization to the classical population genetic treatment of pairwise epistasis that yields expressions for epistasis among arbitrary subsets of mutations of all orders (pairwise, three-way, etc.). Our approach reveals substantial higher-order epistasis in almost every published fitness landscape. Furthermore we demonstrate that higher-order epistasis is critically important in two systems we know best. We conclude that higher-order epistasis deserves empirical and theoretical attention from evolutionary geneticists.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.