Exploring genetic suppression interactions on a global scale

Jolanda Van Leeuwen, Carles Pons, Joseph C. Mellor, Takafumi N. Yamaguchi, Helena Friesen, John Koschwanez, Mojca Mattiazzi Ušaj, Maria Pechlaner, Mehmet Takar, Matej Ušaj, Benjamin Vander Sluis, Kerry Andrusiak, Pritpal Bansal, Anastasia Baryshnikova, Claire E. Boone, Jessica Cao, Atina Cote, Marinella Gebbia, Gene Horecka, Ira HoreckaElena Kuzmin, Nicole Legro, Wendy Liang, Natascha Van Lieshout, Margaret McNee, Bryan Joseph San Luis, Fatemeh Shaeri, Ermira Shuteriqi, Song Sun, Lu Yang, Ji Young Youn, Michael Yuen, Michael Costanzo, Anne Claude Gingras, Patrick Aloy, Chris Oostenbrink, Andrew Murray, Todd R. Graham, Chad L. Myers, Brenda J. Andrews, Frederick P. Roth, Charles Boone

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numberaag0839
JournalScience
Volume354
Issue number6312
DOIs
StatePublished - Nov 4 2016

Bibliographical note

Funding 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.

Publisher Copyright:
Copyright © 2016 by the American Association for the Advancement of Science.

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

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