Prevalent positive epistasis in Escherichia coli and Saccharomyces cerevisiae metabolic networks.
Prevalent positive epistasis in Escherichia coli and Saccharomyces cerevisiae metabolic networks.
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上位性是指基因间的相互作用。尽管来自模式生物的高通量上位性数据正在被生成并用于构建遗传网络，但遗传上位性在多大程度上反映了生物学上有意义的相互作用仍不清楚。我们通过使用通量平衡分析，在大肠杆菌和酿酒杆菌代谢网络内的生化反应之间的积极和消极上位相互作用的硅图来解决这个问题。我们发现，负上位主要发生在功能重叠的非必要反应之间，而正上位通常涉及必要反应，数量丰富，而且令人惊讶的是，经常发生在功能不重叠的反应之间。我们对这些发现进行了机制解释，并对61对酿酒葡萄球菌基因对进行了实验验证。
Epistasis refers to the interaction between genes. Although high-throughput epistasis data from model organisms are being generated and used to construct genetic networks, to what extent genetic epistasis reflects biologically meaningful interactions remains unclear. We address this question by in silico mapping of positive and negative epistatic interactions amongst biochemical reactions within the metabolic networks of E. coli and S. 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 surprisingly, often occurs between reactions without overlapping functions. We offered mechanistic explanations of these findings and experimentally validated them for 61 S. cerevisiae gene pairs.