ArticleMolecular biology and evolution2019
Patterns and Mechanisms of Diminishing Returns from Beneficial Mutations.
Article in Molecular biology and evolution, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Historical contingency limits adaptive diversification in a spatially structured environment.Evolution letters · 2026Article
- EML4-ALK Variant-Specific Genetic Interactions Shape Lung Tumorigenesis.Cancer discovery · 2026Article
- Characterising Heatwave Responses and Climate Driver Impacts Using Multicollinearity-Controlled Generalised Linear Mixed Models in Urban and Forest Trees (2018-2023).Earth systems and environment · 2026Article
- Idiosyncratic evolvability among single-point ribosomal mutants towards multi-aminoglycoside resistance.PLoS genetics · 2025Article
- Soft Modes as a Predictive Framework for Low-Dimensional Biological Systems Across Scales.Annual review of biophysics · 2025Review
- Amyloid-β Clearance with Monoclonal Antibodies: Transforming Alzheimer's Treatment.Current protein & peptide science · 2025Review
- Soft Modes as a Predictive Framework for Low Dimensional Biological Systems across Scales.ArXiv · 2024Article
- Forward-in-time simulation of chromosomal rearrangements: The invisible backbone that sustains long-term adaptation.Molecular ecology · 2024Article
- Article
- Environment-independent distribution of mutational effects emerges from microscopic epistasis.Science (New York, N.Y.) · 2024Article
- Formalizing the law of diminishing returns in metabolic networks using an electrical analogy.Royal Society open science · 2024Article
- Patterns of Fitness and Gene Expression Epistasis Generated by Beneficial Mutations in the rho and rpoB Genes of Escherichia coli during High-Temperature Adaptation.Molecular biology and evolution · 2024Article
- Environment-independent distribution of mutational effects emerges from microscopic epistasis.bioRxiv : the preprint server for biology · 2024Article
- The loci of environmental adaptation in a model eukaryote.Nature communications · 2024Article
- Correlated responses to selection across diverse environments during experimental evolution ofEcology and evolution · 2024Article
- Biophysical principles predict fitness of SARS-CoV-2 variants.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Global epistasis in plasmid-mediated antimicrobial resistance.Molecular systems biology · 2024Review
- Biophysical principles predict fitness of SARS-CoV-2 variants.bioRxiv : the preprint server for biology · 2024Article
- Environmental modulation of global epistasis in a drug resistance fitness landscape.Nature communications · 2023Article
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2 authors.
Funding
Abstract
Diminishing returns epistasis causes the benefit of the same advantageous mutation smaller in fitter genotypes and is frequently observed in experimental evolution. However, its occurrence in other contexts, environment dependence, and mechanistic basis are unclear. Here, we address these questions using 1,005 sequenced segregants generated from a yeast cross. Under each of 47 examined environments, 66-92% of tested polymorphisms exhibit diminishing returns epistasis. Surprisingly, improving environment quality also reduces the benefits of advantageous mutations even when fitness is controlled for, indicating the necessity to revise the global epistasis hypothesis. We propose that diminishing returns originates from the modular organization of life where the contribution of each functional module to fitness is determined jointly by the genotype and environment and has an upper limit, and demonstrate that our model predictions match empirical observations. These findings broaden the concept of diminishing returns epistasis, reveal its generality and potential cause, and have important evolutionary implications.
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