Functional repurposing revealed by comparing S. pombe and S. cerevisiae genetic interactions

Adam Frost, Marc G. Elgort, Onn Brandman, Clinton Ives, Sean Collins, Lakshmi Miller-Vedam, Jimena Weibezahn, Marco Y. Hein, Ina Poser, Matthias Mann, Anthony A. Hyman, Jonathan S. Weissman

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

We 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.

Original languageEnglish (US)
Pages (from-to)1339-1352
Number of pages14
JournalCell
Volume149
Issue number6
DOIs
StatePublished - Jun 8 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Frost, A., Elgort, M. G., Brandman, O., Ives, C., Collins, S., Miller-Vedam, L., Weibezahn, J., Hein, M. Y., Poser, I., Mann, M., Hyman, A. A., & Weissman, J. S. (2012). Functional repurposing revealed by comparing S. pombe and S. cerevisiae genetic interactions. Cell, 149(6), 1339-1352. https://doi.org/10.1016/j.cell.2012.04.028