Hierarchical Modularity and the Evolution of Genetic Interactomes across Species

被引：151

作者：

Ryan, Colm J. ^{[1
,4
,5
]}

Roguev, Assen ^{[1
,4
]}

Patrick, Kristin ^{[1
,2
,4
]}

Xu, Jiewei ^{[1
,4
]}

Jahari, Harlizawati ^{[1
,4
,7
]}

Tong, Zongtian ^{[8
]}

Beltrao, Pedro ^{[1
,4
]}

Shales, Michael ^{[1
,4
]}

Qu, Hong ^{[1
,4
]}

Collins, Sean R. ^{[9
]}

Kliegman, Joseph I. ^{[1
,4
,10
]}

Jiang, Lingli ^{[3
,4
]}

Kuo, Dwight ^{[11
,12
]}

Tosti, Elena ^{[13
]}

Kim, Hyun-Soo ^{[13
]}

Edelmann, Winfried ^{[13
]}

Keogh, Michael-Christopher ^{[13
]}

Greene, Derek ^{[5
]}

Tang, Chao ^{[3
,4
,14
]}

Cunningham, Padraig ^{[5
]}

Shokat, Kevan M. ^{[1
,4
,10
]}

Cagney, Gerard ^{[6
]}

Svensson, J. Peter ^{[15
]}

Guthrie, Christine ^{[2
]}

Espenshade, Peter J. ^{[8
]}

Ideker, Trey ^{[11
,12
]}

Krogan, Nevan J. ^{[1
,4
,16
]}

机构：

[1] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA

[3] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA

[4] Calif Inst Quantitat Biosci, QB3, San Francisco, CA 94158 USA

[5] Natl Univ Ireland Univ Coll Dublin, Sch Comp Sci & Informat, Dublin 4, Ireland

[6] Natl Univ Ireland Univ Coll Dublin, Sch Biomol & Biomed Sci, Dublin 4, Ireland

[7] Minist Sci Technol & Innovat MOSTI, Malaysian Inst Pharmaceut & Nutraceut, Gelugor 11700, Penang, Malaysia

[8] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA

[9] Dept Chem & Syst Biol, Stanford, CA 94305 USA

[10] Howard Hughes Med Inst, San Francisco, CA 94158 USA

[11] Univ Calif San Diego, Dept Med & Bioengn, La Jolla, CA 92093 USA

[12] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

[13] Albert Einstein Coll Med, Dept Cell Biol, New York, NY 10461 USA

[14] Peking Univ, Ctr Quantitat Biol, Beijing 100871, Peoples R China

[15] Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden

[16] J David Gladstone Inst, San Francisco, CA 94158 USA

来源：

MOLECULAR CELL | 2012年 / 46卷 / 05期

基金：

爱尔兰科学基金会;

关键词：

SACCHAROMYCES-CEREVISIAE; PROTEIN COMPLEXES; INTERACTION MAP; FUNCTIONAL-ORGANIZATION; MISSING HERITABILITY; HIGH-THROUGHPUT; REVEALS LINKS; YEAST; EPISTASIS; NETWORK;

D O I：

10.1016/j.molcel.2012.05.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：691 / 704

页数：14

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