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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

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,Gut

doi

10.1016/j.molcel.2012.05.028

subject

Has Abstract

pub_date

2012-06-08 00:00:00

pages

691-704

issue

5

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(12)00444-3

journal_volume

46

pub_type

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