The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
PLoS Comput Biol. 2011 Feb;7(2):e1001092. doi: 10.1371/journal.pcbi.1001092. Epub 2011 Feb 24.
If perturbing two genes together has a stronger or weaker effect than expected, they are said to genetically interact. Genetic interactions are important because they help map gene function, and functionally related genes have similar genetic interaction patterns. Mapping quantitative (positive and negative) genetic interactions on a global scale has recently become possible. This data clearly shows groups of genes connected by predominantly positive or negative interactions, termed monochromatic groups. These groups often correspond to functional modules, like biological processes or complexes, or connections between modules. However it is not yet known how these patterns globally relate to known functional modules. Here we systematically study the monochromatic nature of known biological processes using the largest quantitative genetic interaction data set available, which includes fitness measurements for ∼5.4 million gene pairs in the yeast Saccharomyces cerevisiae. We find that only 10% of biological processes, as defined by Gene Ontology annotations, and less than 1% of inter-process connections are monochromatic. Further, we show that protein complexes are responsible for a surprisingly large fraction of these patterns. This suggests that complexes play a central role in shaping the monochromatic landscape of biological processes. Altogether this work shows that both positive and negative monochromatic patterns are found in known biological processes and in their connections and that protein complexes play an important role in these patterns. The monochromatic processes, complexes and connections we find chart a hierarchical and modular map of sensitive and redundant biological systems in the yeast cell that will be useful for gene function prediction and comparison across phenotypes and organisms. Furthermore the analysis methods we develop are applicable to other species for which genetic interactions will progressively become more available.
如果同时干扰两个基因的效果比预期的要强或弱，那么这两个基因就被认为存在遗传相互作用。遗传相互作用很重要，因为它们有助于确定基因的功能，并且功能相关的基因具有相似的遗传相互作用模式。最近，在全球范围内对定量（正的和负的）遗传相互作用进行映射已成为可能。这些数据清楚地显示了通过主要的正或负相互作用连接的基因组，称为单色组。这些组通常对应于功能模块，如生物过程或复合物，或模块之间的连接。然而，目前还不知道这些模式如何与已知的功能模块在全局上相关。在这里，我们使用最大的定量遗传相互作用数据集系统地研究了已知生物过程的单色性质，该数据集包括酵母酿酒酵母中约 540 万个基因对的适合度测量。我们发现，只有 10%的生物过程（根据基因本体论注释定义）和不到 1%的过程间连接是单色的。此外，我们还表明，蛋白质复合物是造成这些模式的一个重要原因。这表明复合物在塑造生物过程的单色景观中起着核心作用。总的来说，这项工作表明，正的和负的单色模式都存在于已知的生物过程及其连接中，并且蛋白质复合物在这些模式中起着重要的作用。我们发现的单色过程、复合物和连接描绘了酵母细胞中敏感和冗余生物系统的层次化和模块化图谱，这对于基因功能预测以及在表型和生物体之间进行比较将非常有用。此外，我们开发的分析方法适用于其他具有遗传相互作用的物种，这些物种的遗传相互作用将越来越多地被发现。
