Ryan, Colm J.Colm J.RyanRoguev, AssenAssenRoguevPatrick, KristinKristinPatrickGreene, DerekDerekGreeneCunningham, PádraigPádraigCunninghamCagney, GerardGerardCagneyet al.2013-07-222013-07-222012 Elsev2012-06Molecular cellhttp://hdl.handle.net/10197/4461To date, cross-species comparisons of genetic interactomes have been restricted to small or functionally related gene sets, limiting our ability to infer evolutionary trends. To facilitate a more comprehensive analysis, we constructed a genome-scale epistasis map (E-MAP) for the fission yeast Schizosaccharomyces pombe, providing phenotypic signatures for ~60% of the nonessential genome. Using these signatures, we generated a catalog of 297 functional modules, and we assigned function to 144 previously uncharacterized genes, including mRNA splicing and DNA damage checkpoint factors. Comparison with an integrated genetic interactome from the budding yeast Saccharomyces cerevisiae revealed a hierarchical model for the evolution of genetic interactions, with conservation highest within protein complexes, lower within biological processes, and lowest between distinct biological processes. Despite the large evolutionary distance and extensive rewiring of individual interactions, both networks retain conserved features and display similar levels of functional crosstalk between biological processes, suggesting general design principles of genetic interactomes.enThis is the author’s version of a work that was accepted for publication in Molecular Cell. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Volume 46, Issue 5, 8 June 2012, Pages 691–704) DOI:10.1016/j.molcel.2012.05.028 Elsevier Inc.Genetic interactionsEpistatic interactionsSchizosaccharomyces pombeSaccharomyces cerevisiaeJournal Article46569170410.1016/j.molcel.2012.05.0282013-07-01https://creativecommons.org/licenses/by-nc-nd/3.0/ie/