Functional Repurposing Revealed by Comparing S. pombe and S. cerevisiae Genetic Interactions

SummaryWe present a genetic interaction map of pairwise measures including ∼40% of nonessential S. pombe genes. By comparing interaction maps for fission and budding yeast, we confirmed widespread conservation of genetic relationships within and between complexes and pathways. However, we identified an important subset of orthologous complexes that have undergone functional “repurposing”: the evolution of divergent functions and partnerships. We validated three functional repurposing events in S. pombe and mammalian cells and discovered that (1) two lumenal sensors of misfolded ER proteins, the kinase/nuclease Ire1 and the glucosyltransferase Gpt1, act together to mount an ER stress response; (2) ESCRT factors regulate spindle-pole-body duplication; and (3) a membrane-protein phosphatase and kinase complex, the STRIPAK complex, bridges the cis-Golgi, the centrosome, and the outer nuclear membrane to direct mitotic progression. Each discovery opens new areas of inquiry and—together—have implications for model organism-based research and the evolution of genetic systems.

Graphical AbstractFigure optionsDownload high-quality image (196 K)Download as PowerPoint slideHighlights
► Genetic interaction data set for 40% of nonessential S. pombe genes
► Mapping of functional divergence between orthologous genes in two eukaryotes
► Discovery of ER stress-response and spindle-pole-body duplication determinants
► Mitotic STRIPAK signaling complexes bridge centrosomes, nuclear envelope, and Golgi