ArticleeLife2021
Emergence and propagation of epistasis in metabolic networks.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Polymorphisms in a bacterial signalling pathway alter evolutionary routes of antibiotic resistance in Escherichia coli.PLoS biology · 2026Article
- Genotype-fitness mapping of adaptive mutants reveals shifting low-dimensional structure across divergent environments.PLoS biology · 2026Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- Article
- Article
- Epistatic hotspots organize antibody fitness landscape and boost evolvability.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Environment-independent distribution of mutational effects emerges from microscopic epistasis.Science (New York, N.Y.) · 2024Article
- Environment-independent distribution of mutational effects emerges from microscopic epistasis.bioRxiv : the preprint server for biology · 2024Article
- A continuous epistasis model for predicting growth rate given combinatorial variation in gene expression and environment.Cell systems · 2024Article
- Coupling High-Throughput and Targeted Screening for Identification of Nonobvious Metabolic Engineering Targets.ACS synthetic biology · 2024Article
- Environmental modulation of global epistasis in a drug resistance fitness landscape.Nature communications · 2023Article
- DeconstructingiScience · 2023Article
- The design of mapping populations: Impacts of geographic scale on genetic architecture and mapping efficacy for defense and immunity.Current opinion in plant biology · 2023Review
- Epistasis and evolution: recent advances and an outlook for prediction.BMC biology · 2023Review
- A tractable physical model for the yeast polarity predicts epistasis and fitness.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Fitness of evolving bacterial populations is contingent on deep and shallow history but only shallow history creates predictable patterns.Proceedings. Biological sciences · 2022Article
- On the incongruence of genotype-phenotype and fitness landscapes.PLoS computational biology · 2022Article
- Challenges and potential solutions for studying the genetic and phenotypic architecture of adaptation in microbes.Current opinion in genetics & development · 2022Review
- Mutational robustness changes during long-term adaptation in laboratory budding yeast populations.eLife · 2022Article
- Idiosyncratic epistasis leads to global fitness-correlated trends.Science (New York, N.Y.) · 2022Article
Corrections and comments
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Authors and funding
1 author.
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Abstract
Epistasis is often used to probe functional relationships between genes, and it plays an important role in evolution. However, we lack theory to understand how functional relationships at the molecular level translate into epistasis at the level of whole-organism phenotypes, such as fitness. Here, I derive two rules for how epistasis between mutations with small effects propagates from lower- to higher-level phenotypes in a hierarchical metabolic network with first-order kinetics and how such epistasis depends on topology. Most importantly, weak epistasis at a lower level may be distorted as it propagates to higher levels. Computational analyses show that epistasis in more realistic models likely follows similar, albeit more complex, patterns. These results suggest that pairwise inter-gene epistasis should be common, and it should generically depend on the genetic background and environment. Furthermore, the epistasis coefficients measured for high-level phenotypes may not be sufficient to fully infer the underlying functional relationships.
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Registered trials
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