Commensurate distances and similar motifs in genetic congruence and protein interaction networks in yeast
Commensurate distances and similar motifs in genetic congruence and protein interaction networks in yeast
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DOI：
10.1186/1471-2105-6-270
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发表时间：
2005-11-09
影响因子：
3
通讯作者：
Bader, JS
中科院分区：
文献类型：
--
作者：
Ye, P;Peyser, BD;Bader, JS
背景：在遗传相互作用中，双突变体的表型不同于潜在单突变体的组合表型。当单突变体没有生长缺陷，而双突变体是致命的或生长缓慢时，这种相互作用称为合成致死性或合成适应度。这些基因相互作用揭示了基因冗余和补偿途径。最近可获得的酿酒酵母遗传相互作用和蛋白质相互作用的大规模数据集为阐明生物途径的拓扑结构以及基因如何在这些途径中起作用提供了独特的机会。结果：我们将同余基因定义为具有相似遗传相互作用伙伴的基因对，并通过将同余基因连接起来构建了一个遗传同余网络。通过比较遗传互作、遗传一致性和蛋白质互作三种网络的路径长度，我们发现高遗传一致性不仅与蛋白质直接相互作用连锁相关，而且与蛋白质相互作用网络具有相称的距离。然而，在遗传和蛋白质相互作用网络之间没有观察到一致的距离。我们还证明，同余和蛋白质网络富含表明网络传递性的基序，而遗传网络同时具有传递性（三角形）和非传递性（正方形）基序类型。这些结果表明，酵母细胞对基因缺失的稳健性部分是由于两个互补途径（方形基序）或三个互补途径，其中任何两个都是生存所必需的（三角形基序）。结论：遗传一致性在预测蛋白质相互作用和功能关联方面优于遗传互作。遗传相互作用对通常属于平行补偿通路，可以产生传递基序（需要三条通路中的任意两条）或不可传递基序（需要两条通路中的任何一条）。
Background: In a genetic interaction, the phenotype of a double mutant differs from the combined phenotypes of the underlying single mutants. When the single mutants have no growth defect, but the double mutant is lethal or exhibits slow growth, the interaction is termed synthetic lethality or synthetic fitness. These genetic interactions reveal gene redundancy and compensating pathways. Recently available large-scale data sets of genetic interactions and protein interactions in Saccharomyces cerevisiae provide a unique opportunity to elucidate the topological structure of biological pathways and how genes function in these pathways.Results: We have defined congruent genes as pairs of genes with similar sets of genetic interaction partners and constructed a genetic congruence network by linking congruent genes. By comparing path lengths in three types of networks (genetic interaction, genetic congruence, and protein interaction), we discovered that high genetic congruence not only exhibits correlation with direct protein interaction linkage but also exhibits commensurate distance with the protein interaction network. However, consistent distances were not observed between genetic and protein interaction networks. We also demonstrated that congruence and protein networks are enriched with motifs that indicate network transitivity, while the genetic network has both transitive (triangle) and intransitive (square) types of motifs. These results suggest that robustness of yeast cells to gene deletions is due in part to two complementary pathways (square motif) or three complementary pathways, any two of which are required for viability (triangle motif).Conclusion: Genetic congruence is superior to genetic interaction in prediction of protein interactions and function associations. Genetically interacting pairs usually belong to parallel compensatory pathways, which can generate transitive motifs (any two of three pathways needed) or intransitive motifs (either of two pathways needed).