Decourty Laurence, Saveanu Cosmin, Zemam Kenza, Hantraye Florence, Frachon Emmanuel, Rousselle Jean-Claude, Fromont-Racine Micheline, Jacquier Alain
Institut Pasteur, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, Unité de Recherche Associée 2171, Paris Cedex 15, France.
Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5821-6. doi: 10.1073/pnas.0710533105. Epub 2008 Apr 11.
Describing at a genomic scale how mutations in different genes influence one another is essential to the understanding of how genotype correlates with phenotype and remains a major challenge in biology. Previous studies pointed out the need for accurate measurements of not only synthetic but also buffering interactions in the characterization of genetic networks and functional modules. We developed a sensitive and efficient method that allows such measurements at a genomic scale in yeast. In a pilot experiment (41 genome-wide screens), we quantified the fitness of 140,000 double deletion strains relative to the corresponding single mutants and identified many genetic interactions. In addition to synthetic growth defects (validated experimentally with factors newly identified as genetically interfering with mRNA degradation), most of the identified genetic interactions measured weak epistatic effects. These weak effects, rarely meaningful when considered individually, were crucial to defining specific signatures for many gene deletions and had a major contribution in defining clusters of functionally related genes.
在基因组尺度上描述不同基因中的突变如何相互影响，对于理解基因型与表型的关联至关重要，并且仍然是生物学中的一项重大挑战。先前的研究指出，在遗传网络和功能模块的表征中，不仅需要准确测量合成相互作用，还需要测量缓冲相互作用。我们开发了一种灵敏且高效的方法，能够在酵母中进行基因组尺度的此类测量。在一项先导实验（41次全基因组筛选）中，我们相对于相应的单突变体对140,000个双缺失菌株的适应性进行了量化，并鉴定出许多遗传相互作用。除了合成生长缺陷（通过新鉴定出的对mRNA降解具有遗传干扰作用的因子进行实验验证）外，大多数鉴定出的遗传相互作用测量的是微弱的上位效应。这些微弱效应单独考虑时很少有意义，但对于定义许多基因缺失的特定特征至关重要，并且在定义功能相关基因簇方面发挥了主要作用。
