The strength of genetic interactions scales weakly with mutational effects

Genome Biology

Jeff Gore¹  Andrea Velenich¹ 

[1] Department of Physics, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA

关键词: Yeast;    Genetic interactions;    Fitness landscapes;    Evolution;    Epistasis;   

Others  :  864139
DOI  :  10.1186/gb-2013-14-7-r76

 received in 2013-02-11, accepted in 2013-07-26,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Velenich et al.; licensee BioMed Central Ltd.

【 图 表 】

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