Journal Article

Exploring genetic suppression interactions on a global scale

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

2016

Overview

The genetic background of an organism can influence the overall effects of new genetic variants. Some mutations can amplify a deleterious phenotype, whereas others can suppress it. Starting with a literature survey and expanding into a genomewide assay, van Leeuwen et al. generated a large-scale suppression network in yeast. The data set reveals a set of general properties that can be used to predict suppression interactions. Furthermore, the study provides a template for extending suppression studies to other genes or to more complex organisms. Science , this issue p. 599 A large-scale study in yeast reveals how defects associated with a mutation in one gene can be compensated for by a second mutation in a suppressor gene. 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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Cell Physiological Phenomena - genetics / Chromosome Mapping / Delay / Gene Regulatory Networks / Genes / Genes, Fungal / Genes, Suppressor / Genetic variance / Genetics / Genotype & phenotype / Growth conditions / Literature Reviews / Mutation / Mutations / Networks / Organisms / RESEARCH ARTICLE SUMMARY / Saccharomyces cerevisiae - genetics / Saccharomyces cerevisiae Proteins - genetics / Suppression, Genetic / Yeast / Yeasts