ArticleScience advances2020
Flux, toxicity, and expression costs generate complex genetic interactions in a metabolic pathway.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Exploring archaeal resources for biomass-derived pentose utilization: pathways, extremozymes, and bioprocessing applications.World journal of microbiology & biotechnology · 2026Review
- Downregulation is the dominant effect of new regulatory mutations in a fungal pathogen.Microbial genomics · 2026Article
- D-LIM: A neural network for interpretable gene-gene interactions.PLoS computational biology · 2026Article
- Cryptic phenotypic variation emerges rapidly during the adaptive evolution of a carbapenemase.Nature ecology & evolution · 2026Article
- Idiosyncratic evolvability among single-point ribosomal mutants towards multi-aminoglycoside resistance.PLoS genetics · 2025Article
- Lethal mutagenesis and the transient within-host dynamics of viral adaptation.Virus evolution · 2025Article
- Environment-independent distribution of mutational effects emerges from microscopic epistasis.Science (New York, N.Y.) · 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
- Mutational biases favor complexity increases in protein interaction networks after gene duplication.Molecular systems biology · 2024Article
- Mechanistic causes of sign epistasis and its applications.Frontiers in genetics · 2024Review
- Transcriptome Analysis Reveals the Involvement of Mitophagy and Peroxisome in the Resistance to QoIs inMicroorganisms · 2023Article
- Deep mutational scanning reveals the molecular determinants of RNA polymerase-mediated adaptation and tradeoffs.Nature communications · 2023Article
- A null model for the distribution of fitness effects of mutations.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Environment-dependent epistasis increases phenotypic diversity in gene regulatory networks.Science advances · 2023Article
- Epistasis decreases with increasing antibiotic pressure but not temperature.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- On the incongruence of genotype-phenotype and fitness landscapes.PLoS computational biology · 2022Article
- Environmental selection and epistasis in an empirical phenotype-environment-fitness landscape.Nature ecology & evolution · 2022Article
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Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our ability to predict the impact of mutations on traits relevant for disease and evolution remains severely limited by the dependence of their effects on the genetic background and environment. Even when molecular interactions between genes are known, it is unclear how these translate to organism-level interactions between alleles. We therefore characterized the interplay of genetic and environmental dependencies in determining fitness by quantifying ~4000 fitness interactions between expression variants of two metabolic genes, starting from various environmentally modulated expression levels. We detect a remarkable variety of interactions dependent on initial expression levels and demonstrate that they can be quantitatively explained by a mechanistic model accounting for catabolic flux, metabolite toxicity, and expression costs. Complex fitness interactions between mutations can therefore be predicted simply from their simultaneous impact on a few connected molecular phenotypes.
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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.