@article{92b9e9b524b94d43aa27c62d913cc3ba,
title = "Hierarchical Modularity and the Evolution of Genetic Interactomes across Species",
abstract = "To 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.",
author = "Ryan, {Colm J.} and Assen Roguev and Kristin Patrick and Jiewei Xu and Harlizawati Jahari and Zongtian Tong and Pedro Beltrao and Michael Shales and Hong Qu and Collins, {Sean R.} and Kliegman, {Joseph I.} and Lingli Jiang and Dwight Kuo and Elena Tosti and Kim, {Hyun Soo} and Winfried Edelmann and Keogh, {Michael Christopher} and Derek Greene and Chao Tang and P{\'a}draig Cunningham and Shokat, {Kevan M.} and Gerard Cagney and Svensson, {J. Peter} and Christine Guthrie and Espenshade, {Peter J.} and Trey Ideker and Krogan, {Nevan J.}",
note = "Funding Information: The authors wish to thank members of the Krogan lab and J.E. Haber for helpful discussion. We are grateful to Patrick Kemmermen for support with the online database and the Pombase team for responding to technical queries. This work was supported by grants from QB3@UCSF, the NIH (GM084448, GM084279, GM081879, and GM098101 to N.J.K.; GM085764 and GM084279 to T.I.; GM21119 to C.G.; HL077588 to P.E.; ES019966 and CA013330 to W.E. and M.C.K.) and the Science Foundation Ireland (grant number 08/SRC/I1407 to P.C., D.G., and G.C.). C.R. is supported by the IRCSET-funded Ph.D. program in Bioinformatics and Systems Biology. P.B. is supported by the Human Frontiers Science Program. P.E. is an Established Investigator of the American Heart Association. T.I. is a David and Lucille Packard Fellow. C.G. is an American Cancer Society Research Professor of Molecular Genetics. N.J.K. is a Searle Scholar and a Keck Young Investigator. ",
year = "2012",
month = jun,
day = "8",
doi = "10.1016/j.molcel.2012.05.028",
language = "English (US)",
volume = "46",
pages = "691--704",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "5",
}