Prevalent positive epistasis in Escherichia coli and Saccharomyces cerevisiae metabolic networks.
Epistasis refers to the interaction between genes. Although high-throughput epistasis data from model organisms are being generated and used to construct genetic networks, the extent to which genetic epistasis reflects biologically meaningful interactions remains unclear. We have addressed this question through in silico mapping of positive and negative epistatic interactions amongst biochemical reactions within the metabolic networks of Escherichia coli and Saccharomyces cerevisiae using flux balance analysis. We found that negative epistasis occurs mainly between nonessential reactions with overlapping functions, whereas positive epistasis usually involves essential reactions, is highly abundant and, unexpectedly, often occurs between reactions without overlapping functions. We offer mechanistic explanations of these findings and experimentally validate them for 61 S. cerevisiae gene pairs.
He
Xionglei
X
Department of Ecology and Evolutionary Biology, Ann Arbor, Michigan, USA.
Qian
Wenfeng
W
Wang
Zhi
Z
Li
Ying
Y
Zhang
Jianzhi
J
D016000:Cluster Analysis; D004843:Epistasis, Genetic; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008957:Models, Genetic; D025941:Protein Interaction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
D029968:Escherichia coli Proteins; D029701:Saccharomyces cerevisiae Proteins