Idiosyncratic epistasis leads to global fitness–correlated trends
- 6 May 2022
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 376 (6593), 630-635
- https://doi.org/10.1126/science.abm4774
Abstract
Epistasis can markedly affect evolutionary trajectories. In recent decades, protein-level fitness landscapes have revealed extensive idiosyncratic epistasis among specific mutations. By contrast, other work has found ubiquitous and apparently nonspecific patterns of global diminishing-returns and increasing-costs epistasis among mutations across the genome. Here, we used a hierarchical CRISPR gene drive system to construct all combinations of 10 missense mutations from across the genome in budding yeast and measured their fitness in six environments. We show that the resulting fitness landscapes exhibit global fitness-correlated trends but that these trends emerge from specific idiosyncratic interactions. We thus provide experimental validation of recent theoretical work arguing that fitness-correlated trends can emerge as the generic consequence of idiosyncratic epistasis.This publication has 54 references indexed in Scilit:
- The Environment Affects Epistatic Interactions to Alter the Topology of an Empirical Fitness LandscapePLoS Genetics, 2013
- Genome engineering in Saccharomyces cerevisiae using CRISPR-Cas systemsNucleic Acids Research, 2013
- Natural Polymorphism in BUL2 Links Cellular Amino Acid Availability with Chronological Aging and Telomere Maintenance in YeastPLoS Genetics, 2011
- Negative Epistasis Between Beneficial Mutations in an Evolving Bacterial PopulationScience, 2011
- Diminishing Returns Epistasis Among Beneficial Mutations Decelerates AdaptationScience, 2011
- Reciprocal Sign Epistasis between Frequently Experimentally Evolved Adaptive Mutations Causes a Rugged Fitness LandscapePLoS Genetics, 2011
- GCTA: A Tool for Genome-wide Complex Trait AnalysisAmerican Journal of Human Genetics, 2011
- Exploring protein fitness landscapes by directed evolutionNature Reviews Molecular Cell Biology, 2009
- A Catalog of Neutral and Deleterious Polymorphism in YeastPLoS Genetics, 2008
- Robustness–epistasis link shapes the fitness landscape of a randomly drifting proteinNature, 2006