Department of Ecology and Evolutionary Biology, Ann Arbor, Michigan, USA.
Nat Genet. 2010 Mar;42(3):272-6. doi: 10.1038/ng.524. Epub 2010 Jan 24.
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.
上位性是指基因之间的相互作用。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，对大肠杆菌和酿酒酵母代谢网络中的生化反应之间的正、负上位性相互作用进行了计算机模拟映射，从而解决了这个问题。我们发现，负上位性主要发生在具有重叠功能的非必需反应之间，而正上位性通常涉及必需反应，并且数量非常丰富，出人意料的是，正上位性经常发生在没有重叠功能的反应之间。我们对这些发现提供了机制解释，并通过实验验证了 61 对酿酒酵母基因对。
