Systematic analysis of complex genetic interactions

被引：184

作者：

Kuzmin, Elena ^{[1
,2
,11
]}

VanderSluis, Benjamin ^{[3
]}

Wang, Wen ^{[3
]}

Tan, Guihong ^{[1
]}

Deshpande, Raamesh ^{[3
]}

Chen, Yiqun ^{[1
]}

Usaj, Matej ^{[1
]}

Balint, Attila ^{[1
,4
,12
]}

Usaj, Mojca Mattiazzi ^{[1
]}

van Leeuwen, Jolanda ^{[1
]}

Koch, Elizabeth N. ^{[3
]}

Pons, Carles ^{[3
]}

Dagilis, Andrius J. ^{[5
]}

Pryszlak, Michael ^{[1
]}

YangWang, Jason Zi ^{[1
,2
]}

Hanchard, Julia ^{[1
,2
]}

Riggi, Margot ^{[6
,7
,8
,9
]}

Xu, Kaicong ^{[3
]}

Heydari, Hamed ^{[1
,2
]}

Luis, Bryan-Joseph San ^{[1
]}

Shuteriqi, Ermira ^{[1
]}

Zhu, Hongwei ^{[1
]}

Van Dyk, Nydia ^{[1
]}

Sharifpoor, Sara ^{[1
]}

Costanzo, Michael ^{[1
]}

Loewith, Robbie ^{[6
,8
,9
]}

Caudy, Amy ^{[1
,2
]}

Bolnick, Daniel ^{[5
]}

Brown, Grant W. ^{[1
,4
]}

Andrews, Brenda J. ^{[1
,2
]}

Boone, Charles ^{[1
,2
,10
]}

Myers, Chad L. ^{[3
]}

机构：

[1] Univ Toronto, Donnelly Ctr, 160 Coll St, Toronto, ON M5S 3E1, Canada

[2] Univ Toronto, Dept Mol Genet, 160 Coll St, Toronto, ON M5S 3E1, Canada

[3] Univ Minnesota Twin Cities, Dept Comp Sci & Engn, 200 Union St, Minneapolis, MN 55455 USA

[4] Univ Toronto, Dept Biochem, 160 Coll St, Toronto, ON M5S 3E1, Canada

[5] Univ Texas Austin, Dept Integrat Biol, 1 Univ Stn C0990, Austin, TX 78712 USA

[6] Univ Geneva, Dept Mol Biol, CH-1211 Geneva, Switzerland

[7] Univ Geneva, Dept Biochem, CH-1211 Geneva, Switzerland

[8] IGE3 Inst Genet & Genom Geneva, CH-1211 Geneva, Switzerland

[9] Swiss Natl Ctr Competence Res Programme Chem Biol, CH-1211 Geneva, Switzerland

[10] RIKEN, Ctr Sustainable Resource Sci, Wako, Saitama, Japan

[11] McGill Univ, Rosalind & Morris Goodman Canc Res Ctr, 1160 Ave Pins Ouest, Montreal, PQ H3A 1A3, Canada

[12] Univ Copenhagen, Ctr Chromosome Stabil, Dept Cellular & Mol Med, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark

来源：

SCIENCE | 2018年 / 360卷 / 6386期

基金：

瑞士国家科学基金会; 欧洲研究理事会; 加拿大健康研究院;

关键词：

MISSING HERITABILITY; PROTEIN COMPLEXES; YEAST; LANDSCAPE; EVOLUTION; EPISTASIS; DELETION; GENOME; MODELS; FORM;

D O I：

10.1126/science.aao1729

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

To systematically explore complex genetic interactions, we constructed similar to 200,000 yeast triple mutants and scored negative trigenic interactions. We selected double-mutant query genes across a broad spectrum of biological processes, spanning a range of quantitative features of the global digenic interaction network and tested for a genetic interaction with a third mutation. Trigenic interactions often occurred among functionally related genes, and essential genes were hubs on the trigenic network. Despite their functional enrichment, trigenic interactions tended to link genes in distant bioprocesses and displayed a weaker magnitude than digenic interactions. We estimate that the global trigenic interaction network is similar to 100 times as large as the global digenic network, highlighting the potential for complex genetic interactions to affect the biology of inheritance, including the genotype-to-phenotype relationship.

引用

页数：9

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