ArticleNature communications2023
Environmental modulation of global epistasis in a drug resistance fitness landscape.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 25 citations in OpenAlex.
- Review
- Deconstructing empirical fitness seascapes across scales of granularity.G3 (Bethesda, Md.) · 2026Article
- Article
- Genotype-fitness mapping of adaptive mutants reveals shifting low-dimensional structure across divergent environments.PLoS biology · 2026Article
- Deconstructing empirical fitness seascapes across scales of granularity.bioRxiv : the preprint server for biology · 2026Article
- 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
- Fitness seascapes are necessary for realistic modeling of the evolutionary response to drug therapy.Science advances · 2025Article
- Repeatability of evolution and genomic predictions of temperature adaptation in seed beetles.Nature ecology & evolution · 2025Article
- Environment-independent distribution of mutational effects emerges from microscopic epistasis.Science (New York, N.Y.) · 2024Article
- Context-dependent fitness benefits of antibiotic resistance mutations.Proceedings. Biological sciences · 2024Article
- Environment-independent distribution of mutational effects emerges from microscopic epistasis.bioRxiv : the preprint server for biology · 2024Article
- Global epistasis in plasmid-mediated antimicrobial resistance.Molecular systems biology · 2024Review
- Environmental modulation of global epistasis in a drug resistance fitness landscape.Nature communications · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Interactions between mutations (epistasis) can add substantial complexity to genotype-phenotype maps, hampering our ability to predict evolution. Yet, recent studies have shown that the fitness effect of a mutation can often be predicted from the fitness of its genetic background using simple, linear relationships. This phenomenon, termed global epistasis, has been leveraged to reconstruct fitness landscapes and infer adaptive trajectories in a wide variety of contexts. However, little attention has been paid to how patterns of global epistasis may be affected by environmental variation, despite this variation frequently being a major driver of evolution. This is particularly relevant for the evolution of drug resistance, where antimicrobial drugs may change the environment faced by pathogens and shape their adaptive trajectories in ways that can be difficult to predict. By analyzing a fitness landscape of four mutations in a gene encoding an essential enzyme of P. falciparum (a parasite cause of malaria), here we show that patterns of global epistasis can be strongly modulated by the concentration of a drug in the environment. Expanding on previous theoretical results, we demonstrate that this modulation can be quantitatively explained by how specific gene-by-gene interactions are modified by drug dose. Importantly, our results highlight the need to incorporate potential environmental variation into the global epistasis framework in order to predict adaptation in dynamic environments.
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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.