Feb 25, 2011

Epistatic interaction maps relative to multiple metabolic phenotypes

PLoS Genetics
Evan S Snitkin, Daniel Segrè

Abstract

An epistatic interaction between two genes occurs when the phenotypic impact of one gene depends on another gene, often exposing a functional association between them. Due to experimental scalability and to evolutionary significance, abundant work has been focused on studying how epistasis affects cellular growth rate, most notably in yeast. However, epistasis likely influences many different phenotypes, affecting our capacity to understand cellular functions, biochemical networks adaptation, and genetic diseases. Despite its broad significance, the extent and nature of epistasis relative to different phenotypes remain fundamentally unexplored. Here we use genome-scale metabolic network modeling to investigate the extent and properties of epistatic interactions relative to multiple phenotypes. Specifically, using an experimentally refined stoichiometric model for Saccharomyces cerevisiae, we computed a three-dimensional matrix of epistatic interactions between any two enzyme gene deletions, with respect to all metabolic flux phenotypes. We found that the total number of epistatic interactions between enzymes increases rapidly as phenotypes are added, plateauing at approximately 80 phenotypes, to an overall connectivity that is ...Continue Reading

Mentioned in this Paper

Metabolic Process, Cellular
Biochemical Pathway
Choline
Ethanol
Genetic Disorders Screening
Glycerin
Ethanol Measurement
Imbalance
Genome
Enzymes, antithrombotic

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