Hierarchical Modularity and the Evolution of Genetic Interactomes across Species

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

Research output: Contribution to journalArticle

119 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)691-704
Number of pages14
JournalMolecular Cell
Volume46
Issue number5
DOIs
StatePublished - Jun 8 2012

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Ryan, C. J., Roguev, A., Patrick, K., Xu, J., Jahari, H., Tong, Z., Beltrao, P., Shales, M., Qu, H., Collins, S. R., Kliegman, J. I., Jiang, L., Kuo, D., Tosti, E., Kim, H. S., Edelmann, W., Keogh, M. C., Greene, D., Tang, C., ... Krogan, N. J. (2012). Hierarchical Modularity and the Evolution of Genetic Interactomes across Species. Molecular Cell, 46(5), 691-704. https://doi.org/10.1016/j.molcel.2012.05.028