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Open Access Highly Accessed Research

Unequal evolutionary conservation of human protein interactions in interologous networks

Kevin R Brown12 and Igor Jurisica123*

Author Affiliations

1 Department of Medical Biophysics, University of Toronto, Toronto, Canada M5G 1L7

2 Ontario Cancer Institute, Toronto Medical Discovery Tower, Toronto, Canada M5G 1L7

3 Department of Computer Science, University of Toronto, Toronto, Canada M5G 1L71

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Genome Biology 2007, 8:R95  doi:10.1186/gb-2007-8-5-r95

Published: 29 May 2007

Abstract

Background

Protein-protein interaction (PPI) networks have been transferred between organisms using interologs, allowing model organisms to supplement the interactomes of higher eukaryotes. However, the conservation of various network components has not been fully explored. Unequal conservation of certain network components may limit the ability to fully expand the target interactomes using interologs.

Results

In this study, we transfer high quality human interactions to lower eukaryotes, and examine the evolutionary conservation of individual network components. When human proteins are mapped to yeast, we find a strong positive correlation (r = 0.50, P = 3.9 × 10-4) between evolutionary conservation and the number of interacting proteins, which is also found when mapped to other model organisms. Examining overlapping PPI networks, Gene Ontology (GO) terms, and gene expression data, we are able to demonstrate that protein complexes are conserved preferentially, compared to transient interactions in the network. Despite the preferential conservation of complexes, and the fact that the human interactome comprises an abundance of transient interactions, we demonstrate how transferring human PPIs to yeast augments this well-studied protein interaction network, using the coatomer complex and replisome as examples.

Conclusion

Human proteins, like yeast proteins, show a correlation between the number of interacting partners and evolutionary conservation. The preferential conservation of proteins with higher degree leads to enrichment in protein complexes when interactions are transferred between organisms using interologs.