An inter-species protein-protein interaction network across vast evolutionary distance.
In cellular systems, biophysical interactions between macromolecules underlie a complex web of functional interactions. How biophysical and functional networks are coordinated, whether all biophysical interactions correspond to functional interactions, and how such biophysical-versus-functional network coordination is shaped by evolutionary forces are all largely unanswered questions. Here, we investigate these questions using an "inter-interactome" approach. We systematically probed the yeast and human proteomes for interactions between proteins from these two species and functionally characterized the resulting inter-interactome network. After a billion years of evolutionary divergence, the yeast and human proteomes are still capable of forming a biophysical network with properties that resemble those of intra-species networks. Although substantially reduced relative to intra-species networks, the levels of functional overlap in the yeast-human inter-interactome network uncover significant remnants of co-functionality widely preserved in the two proteomes beyond human-yeast homologs. Our data support evolutionary selection against biophysical interactions between proteins with little or no co-functionality. Such non-functional interactions, however, represent a reservoir from which nascent functional interactions may arise.
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA Department of Biological Sciences, Wright State University, Dayton, OH, USA marc_vidal@dfci.harvard.edu fritz.roth@utoronto.ca brandon.xia@mcgill.ca quan.zhong@wright.edu.
Quan
Q
Zhong
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA Department of Biomedical Engineering, Boston University, Boston, MA, USA Boston University School of Medicine, Boston, MA, USA.
Samuel J
SJ
Pevzner
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Tong
T
Hao
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Yang
Y
Wang
Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona Catalonia, Spain.
Roberto
R
Mosca
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Center for Complex Network Research (CCNR) and Department of Physics, Northeastern University, Boston, MA, USA.
Jörg
http://orcid.org/0000-0002-1583-6404
J
Menche
Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
Mikko
M
Taipale
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Departments of Molecular Genetics and Computer Science, University of Toronto, Toronto, ON, Canada Donnelly Centre, University of Toronto, Toronto, ON, Canada Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON, Canada.
Murat
M
Taşan
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Changyu
C
Fan
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Xinping
X
Yang
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Patrick
P
Haley
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Ryan R
RR
Murray
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Flora
F
Mer
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Fana
F
Gebreab
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Stanley
S
Tam
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Andrew
A
MacWilliams
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Amélie
A
Dricot
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Patrick
P
Reichert
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Balaji
B
Santhanam
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Lila
L
Ghamsari
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Michael A
http://orcid.org/0000-0001-6475-1418
MA
Calderwood
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Thomas
T
Rolland
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Benoit
B
Charloteaux
Whitehead Institute for Biomedical Research, Cambridge, MA, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
Susan
S
Lindquist
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Center for Complex Network Research (CCNR) and Department of Physics, Northeastern University, Boston, MA, USA Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Albert-László
AL
Barabási
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
David E
http://orcid.org/0000-0001-5192-0921
DE
Hill
Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona Catalonia, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
Patrick
P
Aloy
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA.
Michael E
ME
Cusick
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Bioengineering, McGill University, Montreal, QC, Canada marc_vidal@dfci.harvard.edu fritz.roth@utoronto.ca brandon.xia@mcgill.ca quan.zhong@wright.edu.
Yu
Y
Xia
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Departments of Molecular Genetics and Computer Science, University of Toronto, Toronto, ON, Canada Donnelly Centre, University of Toronto, Toronto, ON, Canada Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON, Canada Canadian Institute for Advanced Research, Toronto, ON, Canada marc_vidal@dfci.harvard.edu fritz.roth@utoronto.ca brandon.xia@mcgill.ca quan.zhong@wright.edu.
Frederick P
FP
Roth
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA marc_vidal@dfci.harvard.edu fritz.roth@utoronto.ca brandon.xia@mcgill.ca quan.zhong@wright.edu.
Marc
http://orcid.org/0000-0003-3391-5410
M
Vidal
D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D025941:Protein Interaction Mapping / Q000379:methods*; D020543:Proteome / Q000378:metabolism*
D005656:Fungal Proteins; D020543:Proteome
Cross‐species complementation; Network evolution; Selection