Panorama of ancient metazoan macromolecular complexes.
Macromolecular complexes are essential to conserved biological processes, but their prevalence across animals is unclear. By combining extensive biochemical fractionation with quantitative mass spectrometry, here we directly examined the composition of soluble multiprotein complexes among diverse metazoan models. Using an integrative approach, we generated a draft conservation map consisting of more than one million putative high-confidence co-complex interactions for species with fully sequenced genomes that encompasses functional modules present broadly across all extant animals. Clustering reveals a spectrum of conservation, ranging from ancient eukaryotic assemblies that have probably served cellular housekeeping roles for at least one billion years, ancestral complexes that have accrued contemporary components, and rarer metazoan innovations linked to multicellularity. We validated these projections by independent co-fractionation experiments in evolutionarily distant species, affinity purification and functional analyses. The comprehensiveness, centrality and modularity of these reconstructed interactomes reflect their fundamental mechanistic importance and adaptive value to animal cell systems.
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.|Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA.
Cuihong
C
Wan
Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA.
Blake
B
Borgeson
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Sadhna
S
Phanse
Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA.
Fan
F
Tu
Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA.
Kevin
K
Drew
Department of Medical Biophysics, Toronto, Ontario M5G 1L7, Canada.
Greg
G
Clark
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.|Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Xuejian
X
Xiong
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Olga
O
Kagan
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Julian
J
Kwan
Department of Medical Biophysics, Toronto, Ontario M5G 1L7, Canada.
Alexandr
A
Bezginov
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.|Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Kyle
K
Chessman
Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Swati
S
Pal
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.|Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Graham
G
Cromar
Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA.
Ophelia
O
Papoulas
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Zuyao
Z
Ni
Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA.
Daniel R
DR
Boutz
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Snejana
S
Stoilova
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Pierre C
PC
Havugimana
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Xinghua
X
Guo
Department of Biochemistry, University of Regina, Regina, Saskatchewan S4S 0A2, Canada.
Ramy H
RH
Malty
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Mihail
M
Sarov
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Jack
J
Greenblatt
Department of Biochemistry, University of Regina, Regina, Saskatchewan S4S 0A2, Canada.
Mohan
M
Babu
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.|Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
W Brent
WB
Derry
Department of Medical Biophysics, Toronto, Ontario M5G 1L7, Canada.
Elisabeth R
ER
Tillier
Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA.|Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas 78712, USA.
John B
JB
Wallingford
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.|Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
John
J
Parkinson
Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA.|Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas 78712, USA.
Edward M
EM
Marcotte
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Andrew
A
Emili
D000818:Animals; D066264:Datasets as Topic; D019143:Evolution, Molecular; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism*; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D015203:Reproducibility of Results; D049490:Systems Biology; D053719:Tandem Mass Spectrometry
D046912:Multiprotein Complexes