ArticleeLife2021
Global epistasis emerges from a generic model of a complex trait.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed.
- Epistatic impacts of cis- and trans-regulatory mutations on the distribution of mutational effects for gene expression in Saccharomyces cerevisiae.Molecular biology and evolution · 2026Article
- Function-specific epistasis shapes evolutionary trajectories towards antibiotic resistance.Nature communications · 2026Article
- Inference of fitness landscapes with heterogeneous patterns of epistasis across sites.bioRxiv : the preprint server for biology · 2026Article
- Global epistasis in ecosystems arises from resource constraints.bioRxiv : the preprint server for biology · 2026Article
- Mount Fuji's stubby peak: the genotypic density of additive landscapes near maximal fitness.bioRxiv : the preprint server for biology · 2026Article
- Spontaneous mutation rate and spectrum are modulated by organismal fitness.Science advances · 2026Article
- On learning functions over biological sequence space: relating Gaussian process priors, regularization, and gauge fixing.Journal of mathematical biology · 2026Article
- Ecology of metagenomes: incorporating genotype-to-phenotype maps into ecological models.bioRxiv : the preprint server for biology · 2026Article
- Origins and breadth of pairwise epistasis in an α-helix of β-lactamase TEM-1.Nature communications · 2026Article
- Experimental Evolution of Yeast Reveals Trade-offs Between Early and Late Stationary Phase.bioRxiv : the preprint server for biology · 2026Article
- Functional bottlenecks can emerge from non-epistatic underlying traits.PLoS computational biology · 2026Article
- Evolutionary pathways in epistatic mechanical networks.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Inference and Visualization of Complex Genotype-Phenotype Maps.Molecular biology and evolution · 2026Article
- Experimental evolution in an era of molecular manipulation.Nature reviews. Genetics · 2026Review
- Environment-by-Environment Interactions Differ Across Genetic Backgrounds.Molecular biology and evolution · 2025Article
- Global epistasis in budding yeast driven by many natural variants whose effects scale with fitness.Genetics · 2025Article
- Compensatory evolution to DNA replication stress is robust to nutrient availability.Molecular systems biology · 2025Article
- Distinguishing direct interactions from global epistasis using rank statistics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Ecological diversification in rapidly evolving populations.bioRxiv : the preprint server for biology · 2025Article
16 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
2 authors.
Funding
Abstract
Epistasis between mutations can make adaptation contingent on evolutionary history. Yet despite widespread 'microscopic' epistasis between the mutations involved, microbial evolution experiments show consistent patterns of fitness increase between replicate lines. Recent work shows that this consistency is driven in part by global patterns of diminishing-returns and increasing-costs epistasis, which make mutations systematically less beneficial (or more deleterious) on fitter genetic backgrounds. However, the origin of this 'global' epistasis remains unknown. Here, we show that diminishing-returns and increasing-costs epistasis emerge generically as a consequence of pervasive microscopic epistasis. Our model predicts a specific quantitative relationship between the magnitude of global epistasis and the stochastic effects of microscopic epistasis, which we confirm by reanalyzing existing data. We further show that the distribution of fitness effects takes on a universal form when epistasis is widespread and introduce a novel fitness landscape model to show how phenotypic evolution can be repeatable despite sequence-level stochasticity.
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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.