  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.
