Institut Pasteur, Genetique des Interactions Macromoleculaires, Centre National de la Recherche Scientifique, Unite de Recherche Associee 2171, Paris Cedex 15, France-
Abstract: 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-