The strength of genetic interactions scales weakly with mutational effects
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gb-2013-14-7-r76.pdf
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3.87 MB
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Checksum (MD5)
af2e21274daa631ee094ce56598e9890
Author(s)
Velenich, Andrea
Gore, Jeff
Date Issued
July 2013
Journal
Genome Biology
Publisher
BioMed Central Ltd
Citation
Velenich, Andrea, and Jeff Gore. “The Strength of Genetic Interactions Scales Weakly with Mutational Effects.” Genome Biology 14.7 (2013): R76.
Version
Final published version
Abstract
Background:
Genetic 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.
Results:
We 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.
Conclusions:
Although 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.
MIT Department
Massachusetts Institute of Technology. Department of Physics
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1186/gb-2013-14-7-r76
