Functional repurposing revealed by comparing S. pombe and S. cerevisiae genetic interactions.
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.
Department of Biochemistry, Huntsman Cancer Institute, University of Utah, School of Medicine, Salt Lake City, 84112, USA. frost@biochem.utah.edu
Adam
A
Frost
Marc G
MG
Elgort
Onn
O
Brandman
Clinton
C
Ives
Sean R
SR
Collins
Lakshmi
L
Miller-Vedam
Jimena
J
Weibezahn
Marco Y
MY
Hein
Ina
I
Poser
Matthias
M
Mann
Anthony A
AA
Hyman
Jonathan S
JS
Weissman
D005075:Biological Evolution; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D004843:Epistasis, Genetic; D008562:Membrane Glycoproteins; D008938:Mitosis; D046912:Multiprotein Complexes / Q000378:metabolism; D060066:Protein Interaction Maps; D017346:Protein Serine-Threonine Kinases; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D008941:Spindle Apparatus; D056811:Unfolded Protein Response
D056827:Endosomal Sorting Complexes Required for Transport; D008562:Membrane Glycoproteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; C082863:IRE1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases