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.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
Colm J
CJ
Ryan
Assen
A
Roguev
Kristin
K
Patrick
Jiewei
J
Xu
Harlizawati
H
Jahari
Zongtian
Z
Tong
Pedro
P
Beltrao
Michael
M
Shales
Hong
H
Qu
Sean R
SR
Collins
Joseph I
JI
Kliegman
Lingli
L
Jiang
Dwight
D
Kuo
Elena
E
Tosti
Hyun-Soo
HS
Kim
Winfried
W
Edelmann
Michael-Christopher
MC
Keogh
Derek
D
Greene
Chao
C
Tang
Pádraig
P
Cunningham
Kevan M
KM
Shokat
Gerard
G
Cagney
J Peter
JP
Svensson
Christine
C
Guthrie
Peter J
PJ
Espenshade
Trey
T
Ideker
Nevan J
NJ
Krogan
D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D005800:Genes, Fungal; D016681:Genome, Fungal; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity