network evolution rewiring and signatures of conservation in signaling网络进化重新布线和签名的保护信号.pdfVIP

Network Evolution: Rewiring and Signatures of Conservation in Signaling Mark G. F. Sun1., Martin Sikora2,3,4.¤, Michael Costanzo2,3, Charles Boone2,3, Philip M. Kim1,2,3,5* 1 Department of Computer Science, University of Toronto, Toronto, Canada, 2 Banting and Best Department of Medical Research, University of Toronto, Toronto, Canada, 3 Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada, 4 Institut de Biologia Evolutiva (UPF-CSIC), CEXS-UPF-PRBB, Barcelona, Spain, 5 Department of Molecular Genetics, University of Toronto, Toronto, Canada Abstract The analysis of network evolution has been hampered by limited availability of protein interaction data for different organisms. In this study, we investigate evolutionary mechanisms in Src Homology 3 (SH3) domain and kinase interaction networks using high-resolution specificity profiles. We constructed and examined networks for 23 fungal species ranging from Saccharomyces cerevisiae to Schizosaccharomyces pombe. We quantify rates of different rewiring mechanisms and show that interaction change through binding site evolution is faster than through gene gain or loss. We found that SH3 interactions evolve swiftly, at rates similar to those found in phosphoregulation evolution. Importantly, we show that interaction changes are sufficiently rapid to exhibit saturation phenomena at the observed timescales. Finally, focusing on the SH3 interaction network, we observe extensive clustering of binding sites on target proteins by SH3 domains and a strong correlation between the number of domains that bind a target protein (target in-degree) and interaction conservation. The relationship between in-degree and interaction conservation is driven by two different effects, namely the number of clusters that correspond to i