Cargando…

The strength of genetic interactions scales weakly with mutational effects

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 ha...

Descripción completa

Detalles Bibliográficos
Autores principales: Velenich, Andrea, Gore, Jeff
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053755/
https://www.ncbi.nlm.nih.gov/pubmed/23889884
http://dx.doi.org/10.1186/gb-2013-14-7-r76
_version_ 1782320432256385024
author Velenich, Andrea
Gore, Jeff
author_facet Velenich, Andrea
Gore, Jeff
author_sort Velenich, Andrea
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4053755
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-40537552014-06-12 The strength of genetic interactions scales weakly with mutational effects Velenich, Andrea Gore, Jeff Genome Biol Research 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. BioMed Central 2013 2013-07-26 /pmc/articles/PMC4053755/ /pubmed/23889884 http://dx.doi.org/10.1186/gb-2013-14-7-r76 Text en Copyright © 2013 Velenich et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Velenich, Andrea
Gore, Jeff
The strength of genetic interactions scales weakly with mutational effects
title The strength of genetic interactions scales weakly with mutational effects
title_full The strength of genetic interactions scales weakly with mutational effects
title_fullStr The strength of genetic interactions scales weakly with mutational effects
title_full_unstemmed The strength of genetic interactions scales weakly with mutational effects
title_short The strength of genetic interactions scales weakly with mutational effects
title_sort strength of genetic interactions scales weakly with mutational effects
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053755/
https://www.ncbi.nlm.nih.gov/pubmed/23889884
http://dx.doi.org/10.1186/gb-2013-14-7-r76
work_keys_str_mv AT velenichandrea thestrengthofgeneticinteractionsscalesweaklywithmutationaleffects
AT gorejeff thestrengthofgeneticinteractionsscalesweaklywithmutationaleffects
AT velenichandrea strengthofgeneticinteractionsscalesweaklywithmutationaleffects
AT gorejeff strengthofgeneticinteractionsscalesweaklywithmutationaleffects