Hierarchical Modularity and the Evolution of Genetic Interactomes across Species

作者：Ryan Colm J; Roguev Assen; Patrick Kristin; Xu Jiewei; Jahari Harlizawati; Tong Zongtian; Beltrao Pedro; Shales Michael; Qu Hong; Collins Sean R; Kliegman Joseph I; Jiang Lingli; Kuo Dwight; Tosti Elena; Kim Hyun Soo; Edelmann Winfried; Keogh Michael Christopher; Greene Derek; Tang Chao; Cunningham Padraig; Shokat Kevan M; Cagney Gerard; Svensson J Peter; Guthrie Christine; Espenshade Peter J; Ideker Trey; Krogan Nevan J^*

来源：Molecular Cell, 2012, 46(5): 691-704.

DOI：10.1016/j.molcel.2012.05.028

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 similar to 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.

• 出版日期2012-6-8
• 单位北京大学