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MBE Advance Access published online on September 15, 2006
Molecular Biology and Evolution, doi:10.1093/molbev/msl121
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© The Author 2006. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted September 12, 2006

Research Article

Preferential Duplication in the Sparse Part of Yeast Protein Interaction Network

Li Li 1, Yingwu Huang 1, Xuefeng Xia 1, and Zhirong Sun 1 *

1 MOE Key Laboratory of Bioinformatics, State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biology, Tsinghua University, Beijing, China

* To whom correspondence should be addressed.
Zhirong Sun, E-mail: sunzhr{at}mail.tsinghua.edu.cn


  Abstract

Gene duplication is an important mechanism driving the evolution of biomolecular network. Thus it is expected that there should be a strong relationship between a gene's duplicability and the interactions of its protein product with other proteins in the network. We studied this question in the context of the protein interaction network of Saccharomyces cerevisiae. We found that duplicates have, on average, significantly lower clustering coefficient (CC) than singletons, and the proportion of duplicates (PD) decreases steadily with CC. Furthermore, using functional annotation data, we observed a strong negative correlation between PD and the mean CC for functional categories. By partitioning the network into modules and assigning each protein a modularity measure Qn, we found that CC of a protein is a reection of its modularity. Moreover, the core components of complexes identified in a recent high-throughput experiment, characterized by high CC, have lower PD than that of the attachments. Subsequently, two types of hub were identified by their degree, CC and Qn. While PD of intra-modular hubs is much less than the network average, PD of inter-modular hubs is comparable to, or even higher than the network average. Our results suggest that high CC, thus high modularity, pose strong evolutionary constraints on gene duplicability, and gene duplication prefer to happen in the sparse part of protein interaction networks.

Keywords: gene duplicability; yeast; clustering coefficient; protein interaction network; modularity; network evolution.
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