Open Access Research article

An evolutionary and structural characterization of mammalian protein complex organization

Philip Wong1, Sonja Althammer1, Andrea Hildebrand1, Andreas Kirschner2, Philipp Pagel12, Bernd Geissler2, Pawel Smialowski12, Florian Blöchl1, Matthias Oesterheld1, Thorsten Schmidt12, Normann Strack1, Fabian J Theis13, Andreas Ruepp1 and Dmitrij Frishman12*

Author Affiliations

1 Helmholtz Center Munich – German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Ingolstädter Landstraße 1 D-85764 Neuherberg, Germany

2 Department of Genome Oriented Bioinformatics, Technische Universität München, Wissenschaftzentrum Weihenstephan, 85350 Freising, Germany

3 Max-Planck-Institute for Dynamics and Self-Organization, Bunsenstrasse 10, 37073 Göttingen, Germany

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BMC Genomics 2008, 9:629  doi:10.1186/1471-2164-9-629

Published: 23 December 2008



We have recently released a comprehensive, manually curated database of mammalian protein complexes called CORUM. Combining CORUM with other resources, we assembled a dataset of over 2700 mammalian complexes. The availability of a rich information resource allows us to search for organizational properties concerning these complexes.


As the complexity of a protein complex in terms of the number of unique subunits increases, we observed that the number of such complexes and the mean non-synonymous to synonymous substitution ratio of associated genes tend to decrease. Similarly, as the number of different complexes a given protein participates in increases, the number of such proteins and the substitution ratio of the associated gene also tends to decrease. These observations provide evidence relating natural selection and the organization of mammalian complexes. We also observed greater homogeneity in terms of predicted protein isoelectric points, secondary structure and substitution ratio in annotated versus randomly generated complexes. A large proportion of the protein content and interactions in the complexes could be predicted from known binary protein-protein and domain-domain interactions. In particular, we found that large proteins interact preferentially with much smaller proteins.


We observed similar trends in yeast and other data. Our results support the existence of conserved relations associated with the mammalian protein complexes.