An inter-species protein-protein interaction network across vast evolutionary distance.
Quan Zhong, Samuel J Pevzner, Tong Hao, Yang Wang, Roberto Mosca, Jörg Menche, Mikko Taipale, Murat Taşan, Changyu Fan, Xinping Yang, Patrick Haley, Ryan R Murray, Flora Mer, Fana Gebreab, Stanley Tam, Andrew MacWilliams, Amélie Dricot, Patrick Reichert, Balaji Santhanam, Lila Ghamsari, Michael A Calderwood, Thomas Rolland, Benoit Charloteaux, Susan Lindquist, Albert-László Barabási, David E Hill, Patrick Aloy, Michael E Cusick, Yu Xia, Frederick P Roth, Marc Vidal
Author Information
Quan 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 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.
Samuel J 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 Department of Biomedical Engineering, Boston University, Boston, MA, USA Boston University School of Medicine, Boston, MA, USA.
Tong 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 Wang: 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.
Roberto Mosca: 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.
Jörg Menche: 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. ORCID
Mikko Taipale: Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
Murat Taşan: 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.
Changyu 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 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 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 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 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 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 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 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 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 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 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 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 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. ORCID
Thomas 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 Charloteaux: 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.
Susan Lindquist: 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.
Albert-László Barabási: 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.
David E Hill: 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. ORCID
Patrick Aloy: 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.
Michael E Cusick: 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.
Yu Xia: 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.
Frederick P Roth: 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.
Marc Vidal: 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. ORCID
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.
