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Published Online September 25, 2008
Science DOI: 10.1126/science.1162609

Research Articles

Submitted on July 1, 2008
Accepted on September 12, 2008

Conservation and Rewiring of Functional Modules Revealed by an Epistasis Map in Fission Yeast

Assen Roguev 1, Sourav Bandyopadhyay 2, Martin Zofall 3, Ke Zhang 3, Tamas Fischer 3, Sean R. Collins 4, Hongjing Qu 1, Michael Shales 1, Han-Oh Park 5, Jacqueline Hayles 6, Kwang-Lae Hoe 7, Dong-Uk Kim 7, Trey Ideker 2*, Shiv I. Grewal 3*, Jonathan S. Weissman 4*, Nevan J. Krogan 1*

1 Department of Cellular and Molecular Pharmacology, University of California–San Francisco, San Francisco, CA 94158, USA.; The California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA 94158, USA.
2 Department of Bioengineering and Program in Bioinformatics, University of California–San Diego, La Jolla, CA 92093, USA.
3 Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
4 Department of Cellular and Molecular Pharmacology, University of California–San Francisco, San Francisco, CA 94158, USA.; The California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA 94158, USA.; Howard Hughes Medical Institute, San Francisco, CA 94158, USA.
5 Bioneer Corporation, Daejeon, Korea.
6 Cell Cycle Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
7 Genomic Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.

* To whom correspondence should be addressed.
Trey Ideker , E-mail: trey{at}bioeng.ucsd.edu
Shiv I. Grewal , E-mail: grewals{at}mail.nih.gov
Jonathan S. Weissman , E-mail: weissman{at}cmp.ucsf.edu
Nevan J. Krogan , E-mail: krogan{at}cmpmail.ucsf.edu

An epistasis map (E-MAP) was constructed in the fission yeast, Schizosaccharomyces pombe, by systematically measuring the phenotypes associated with pairs of mutations. This high-density, quantitative genetic interaction map, focused on various aspects of chromosome function, including transcription regulation and DNA repair/replication. The E-MAP uncovered a novel component of the RNAi machinery (rsh1) and linked the RNAi pathway to several other biological processes. Comparison of the S. pombe E-MAP to an analogous genetic map from the budding yeast revealed that while negative interactions were conserved between genes involved in similar biological processes, positive interactions and overall genetic profiles between pairs of genes coding for physically associated proteins were even more conserved. Hence, conservation occurs at the level of the functional module (i.e., protein complex), but the genetic cross-talk between modules can differ significantly.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)