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Hierarchical modularity and the evolution of genetic interactomes across species.


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.

Pubmed ID: 22681890


  • Ryan CJ
  • Roguev A
  • Patrick K
  • Xu J
  • Jahari H
  • Tong Z
  • Beltrao P
  • Shales M
  • Qu H
  • Collins SR
  • Kliegman JI
  • Jiang L
  • Kuo D
  • Tosti E
  • Kim HS
  • Edelmann W
  • Keogh MC
  • Greene D
  • Tang C
  • Cunningham P
  • Shokat KM
  • Cagney G
  • Svensson JP
  • Guthrie C
  • Espenshade PJ
  • Ideker T
  • Krogan NJ


Molecular cell

Publication Data

June 8, 2012

Associated Grants

  • Agency: NCI NIH HHS, Id: CA013330
  • Agency: NIEHS NIH HHS, Id: ES019966
  • Agency: NIGMS NIH HHS, Id: GM081879
  • Agency: NIGMS NIH HHS, Id: GM084279
  • Agency: NIGMS NIH HHS, Id: GM084448
  • Agency: NIGMS NIH HHS, Id: GM085764
  • Agency: NIGMS NIH HHS, Id: GM098101
  • Agency: NIGMS NIH HHS, Id: GM21119
  • Agency: NHLBI NIH HHS, Id: HL077588
  • Agency: NIAID NIH HHS, Id: P30 AI027763
  • Agency: NIGMS NIH HHS, Id: P50 GM085764
  • Agency: NIGMS NIH HHS, Id: R01 GM084279

Mesh Terms

  • Epistasis, Genetic
  • Evolution, Molecular
  • Gene Expression Regulation, Fungal
  • Gene Regulatory Networks
  • Genes, Fungal
  • Genome, Fungal
  • Saccharomyces cerevisiae
  • Schizosaccharomyces
  • Species Specificity