Differential genetic interactions of yeast stress response MAPK pathways

Abstract Genetic interaction screens have been applied with great success in several organisms to study gene function and the genetic architecture of the cell. However, most studies have been performed under optimal growth conditions even though many functional interactions are known to occur under specific cellular conditions. In this study, we have performed a large-scale genetic interaction analysis in Saccharomyces cerevisiae involving approximately 49 × 1,200 double mutants in the presence of five different stress conditions, including osmotic, oxidative and cell wall-altering stresses. This resulted in the generation of a differential E-MAP (or dE-MAP) comprising over 250,000 measurements of conditional interactions. We found an extensive number of conditional genetic interactions that recapitulate known stress-specific functional associations. Furthermore, we have also uncovered previously unrecognized roles involving the phosphatase regulator Bud14, the histone methylation complex COMPASS and membrane trafficking complexes in modulating the cell wall integrity pathway. Finally, the osmotic stress differential genetic interactions showed enrichment for genes coding for proteins with conditional changes in phosphorylation but not for genes with conditional changes in gene expression. This suggests that conditional genetic interactions are a powerful tool to dissect the functional importance of the different response mechanisms of the cell. Synopsis A differential genetic interaction screen performed in different stress conditions shows that genetic interactions are often context specific. Conditional genetic interactions recapitulate known signalling interactions and can be used to identify novel conditional functional associations. 250,000 measurements of genetic interactions are performed, covering five different stress conditions (e.g. osmotic, oxidative and cell wall-altering stresses). Genetic interactions tend to be context specific and differential genetic interactions identify condition-specific functional associations. Osmotic stress conditional genetic interactions suggest that the post-translational response of the osmotic pathway is more critical and/or specific than the transcriptional response. A differential genetic interaction screen performed in different stress conditions shows that genetic interactions are often context specific. Conditional genetic interactions recapitulate known signalling interactions and can be used to identify novel conditional functional associations.