ArticleGenome biology2013
The strength of genetic interactions scales weakly with mutational effects.
Article in Genome biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Article
- Article
- Improved discovery of genetic interactions using CRISPRiSeq across multiple environments.Genome research · 2019Article
- Evolutionary trade-offs and the structure of polymorphisms.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Article
- Genotypic Complexity of Fisher's Geometric Model.Genetics · 2017Article
- Article
- Epistasis and the Structure of Fitness Landscapes: Are Experimental Fitness Landscapes Compatible with Fisher's Geometric Model?Genetics · 2016Article
- A systematic survey of an intragenic epistatic landscape.Molecular biology and evolution · 2015Article
- Properties of selected mutations and genotypic landscapes under Fisher's geometric model.Evolution; international journal of organic evolution · 2014Article
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenetic interactions pervade every aspect of biology, from evolutionary theory, where they determine the accessibility of evolutionary paths, to medicine, where they can contribute to complex genetic diseases. Until very recently, studies on epistatic interactions have been based on a handful of mutations, providing at best anecdotal evidence about the frequency and the typical strength of genetic interactions. In this study, we analyze a publicly available dataset that contains the growth rates of over five million double knockout mutants of the yeast Saccharomyces cerevisiae.
resultsWe discuss a geometric definition of epistasis that reveals a simple and surprisingly weak scaling law for the characteristic strength of genetic interactions as a function of the effects of the mutations being combined. We then utilized this scaling to quantify the roughness of naturally occurring fitness landscapes. Finally, we show how the observed roughness differs from what is predicted by Fisher's geometric model of epistasis, and discuss the consequences for evolutionary dynamics.
conclusionsAlthough epistatic interactions between specific genes remain largely unpredictable, the statistical properties of an ensemble of interactions can display conspicuous regularities and be described by simple mathematical laws. By exploiting the amount of data produced by modern high-throughput techniques, it is now possible to thoroughly test the predictions of theoretical models of genetic interactions and to build informed computational models of evolution on realistic fitness landscapes.
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