Abstract
Epistasis describes the phenomenon that mutations at different loci do not have independent effects with regard to certain phenotypes. Understanding the global epistatic landscape is vital for many genetic and evolutionary theories. Current knowledge for epistatic dynamics under multiple conditions is limited by the technological difficulties in experimentally screening epistatic relations among genes. We explored this issue by applying flux balance analysis to simulate epistatic landscapes under various environmental perturbations. Specifically, we looked at gene-gene epistatic interactions, where the mutations were assumed to occur in different genes. We predicted that epistasis tends to become more positive from glucose-abundant to nutrient-limiting conditions, indicating that selection might be less effective in removing deleterious mutations in the latter. We also observed a stable core of epistatic interactions in all tested conditions, as well as many epistatic interactions unique to each condition. Interestingly, genes in the stable epistatic interaction network are directly linked to most other genes whereas genes with condition-specific epistasis form a scale-free network. Furthermore, genes with stable epistasis tend to have similar evolutionary rates, whereas this co-evolving relationship does not hold for genes with condition-specific epistasis. Our findings provide a novel genome-wide picture about epistatic dynamics under environmental perturbations.
Highlights
Epistasis refers to the phenomenon wherein mutations of two genes can modify each other’s phenotypic outcomes
We found that differential epistasis had functional importance after performing both Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to compare genes with positive and negative differential epistases through the glucose-abundant to ethanol transition
Positive epistasis alleviates the total harm when multiple deleterious mutations combine together and reduces the effectiveness of natural selection in removing these deleterious mutations, whereas negative epistasis plays the opposite role by increasing the efficiency of purging deleterious mutations by natural selection
Summary
Epistasis refers to the phenomenon wherein mutations of two genes can modify each other’s phenotypic outcomes. It can be positive (alleviating), or negative (aggravating), when a combination of deleterious mutations shows a fitness value that is higher, or lower, than expectation, respectively. A mutation that hampers a pathway’s function may allow for other mutations in the same pathway without a fitness consequence, resulting in positive epistasis. Genes or pathways with redundant functions can give rise to negative epistasis PLOS ONE | DOI:10.1371/journal.pone.0114911 January 27, 2015
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