ArticleMolecular systems biology2015
Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds.
Article in Molecular systems biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Resolving translational challenges in cancer biology through yeast experimental evolution.Cancer metastasis reviews · 2026Review
- Global genetic rewiring during compensatory evolution in the yeast polarity network.EMBO reports · 2026Article
- Compensatory evolution to DNA replication stress is robust to nutrient availability.Molecular systems biology · 2025Article
- Compensatory Evolution Following Deleterious Episodes of GC-biased Gene Conversion in Rodents.Molecular biology and evolution · 2025Article
- Genetic suppression interactions are highly conserved across genetically diverse yeast isolates.G3 (Bethesda, Md.) · 2025Article
- Prevalence of and gene regulatory constraints on transcriptional adaptation in single cells.Genome biology · 2024Article
- Recombination, admixture and genome instability shape the genomic landscape of Saccharomyces cerevisiae derived from spontaneous grape ferments.PLoS genetics · 2024Article
- Prevalence of and gene regulatory constraints on transcriptional adaptation in single cells.bioRxiv : the preprint server for biology · 2023Article
- Gene-by-environment interactions influence the fitness cost of gene copy-number variation in yeast.G3 (Bethesda, Md.) · 2023Article
- Gene-by-environment interactions influence the fitness cost of gene copy-number variation in yeast.bioRxiv : the preprint server for biology · 2023Article
- Overexpression profiling reveals cellular requirements in the context of genetic backgrounds and environments.PLoS genetics · 2023Article
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- AlphaFold, Artificial Intelligence (AI), and Allostery.The journal of physical chemistry. B · 2022Review
- Temperature-Specific and Sex-Specific Fitness Effects of Sympatric Mitochondrial and Mito-Nuclear Variation inInsects · 2022Article
- The Role of Ancestral Duplicated Genes in Adaptation to Growth on Lactate, a Non-Fermentable Carbon Source for the YeastInternational journal of molecular sciences · 2021Article
- Ploidy and recombination proficiency shape the evolutionary adaptation to constitutive DNA replication stress.PLoS genetics · 2021Article
- The cost of evolved constitutiveEcology and evolution · 2021Article
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- Genetic variation in aneuploidy prevalence and tolerance across Saccharomyces cerevisiae lineages.Genetics · 2021Article
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Authors and funding
6 authors.
Funding
Abstract
Since deleterious mutations may be rescued by secondary mutations during evolution, compensatory evolution could identify genetic solutions leading to therapeutic targets. Here, we tested this hypothesis and examined whether these solutions would be universal or would need to be adapted to one's genetic and environmental make-ups. We performed experimental evolutionary rescue in a yeast disease model for the Wiskott-Aldrich syndrome in two genetic backgrounds and carbon sources. We found that multiple aspects of the evolutionary rescue outcome depend on the genotype, the environment, or a combination thereof. Specifically, the compensatory mutation rate and type, the molecular rescue mechanism, the genetic target, and the associated fitness cost varied across contexts. The course of compensatory evolution is therefore highly contingent on the initial conditions in which the deleterious mutation occurs. In addition, these results reveal biologically favored therapeutic targets for the Wiskott-Aldrich syndrome, including the target of an unrelated clinically approved drug. Our results experimentally illustrate the importance of epistasis and environmental evolutionary constraints that shape the adaptive landscape and evolutionary rate of molecular networks.
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