Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene.To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insights into the functional wiring diagram of the cell. In addition to suppressor mutations, we identified frequent secondary mutations, in a subset of genes, that likely cause a delay in the onset of stationary phase, which appears to promote their enrichment within a propagating population.These findings allow us to formulate and quantify general mechanisms of genetic suppression.
Bibliographical noteFunding Information:
We thank G. Fairn, C. Dunn, N. Pascoe, and E. Styles for reagents and technical assistance. This work was primarily supported by grants from the NIH (R01HG005853, R01HG005084, P50HG004233, and U01HG001715) (C.B., B.J.A., C.L.M., and F.P.R.); the Canadian Institutes of Health Research (FDN-143264 and FDN-143265) (C.B. and B.J.A.); the Ontario Research Fund (Research Excellence Grant) (F.P.R.); the Canada Excellence Research Chairs Program (F.P.R.); and a postdoctoral fellowship from the Canadian Institutes of Health Research (J.v.L.). Additional support was provided by the Canadian Institutes of Health Research (FDN-143301) (A.-C.G.), the Vienna Science and Technology Fund (LS08-QM03) (C.O. and M.P.), and the NIH (R01GM107978) (T.R.G.). C.B., B.J.A., F.P.R., and C.L.M. are Senior Fellows in the Canadian Institute for Advanced Research Genetic Networks program. All whole-genome sequencing data are publicly available at NCBI's Sequencing Read Archive, under accession number SRP067030. All suppression interaction data are included in tables S1 and S2.