@misc{oai:ir.soken.ac.jp:00001011,
 author = {牧野, 能士 and マキノ, タカシ and MAKINO, Takashi},
 month = {2016-02-17},
 note = {In Chapter 1, I explained how PPIs were important as one of the major components in biological networks. In particular, I put an emphasis on the importance of evolutionary studies of PPIs.<br />　In Chapter 2, I studied the evolutionary rates of duplicated gene products that were involved with PPIs. When a gene is duplicated, the evolutionary rates of the duplicated gene pair may depend not only on the functional differentiation of their gene products but also on the changes of PPIs in which the proteins are involved. Thus, it is of particular interest to know whether the difference in evolutionary rate exists between a duplicated pair encoding the proteins in the PPI network. It is also interesting to understand how the functional differentiation of these duplicated gene products influences the evolution of PPIs. To answer these questions, I examined the relationship between the evolutionary rate and the functional differentiation of duplicated gene pairs encoding the proteins with their PPI partners. In this examination, I used the carefully selected PPI data of Saccharomyces cerevisiae. For a duplicated pair, I have found that the evolutionary rate of a protein with more PPI partners is much slower than that of the other with fewer PPI partners. Moreover, I estimated the ratios of evolutionary rates for duplicated pairs (a faster rate /a slower rate), and found that the ratios for duplicated pairs sharing the same PPI partners were significantly lower than those for pairs sharing no PPI partners. In particular, I pointed out that there were many pairs sharing no PPI partners in the functional classes such as transcription and protein fate. These results indicate that gene duplication leads to the functional differentiation of the duplicated gene pairs through the losses and/or gains of the PPI partners, resulting in the change in their evolutionary rates.<br />　In Chapter 3, I focused upon how the evolutionary rates of proteins were influenced by the characteristic features of PPIs. Because the recent advancement of molecular technologies enables us to understand actual features of PPIs, it becomes possible to make objective descriptions about the characteristic features of the proteins in the PPI networks. In this analysis, I defined a protein having a larger number of PPI partners of the same functional class as the SF (Same Function) protein, and a protein having a larger number of PPI partners of different functional classes as the DF (Different Function) protein. I also classified proteins in the PPI networks into respective proteins in dense and sparse parts of the PPI network, denoting these proteins as the DP (Dense part) and SP (Sparse Part) proteins, respectively. Because these two classifications were independent of each other, I classified the proteins in PPIs further into the four categories, the SF-DP, SF-SP, DF-DP and DF-SP proteins. Then, I compared the evolutionary rates between the SF and DF proteins, between the DP and SP proteins, and among the four categories. As a result, I found that the DF proteins evolved at a slower rate than the SF proteins. I also found that the SP proteins evolved at a slower rate than the DP proteins. In particular, I pointed out that the DF-SP proteins evolved at the slowest rate in the proteins examined. Because all these differences in the evolutionary rates are statistically significant, it is suggested that the proteins with their PPI partners belonging to different functional classes and occupying a sparse part of the PPI network are under strong functional constraints. It is also implied that those proteins are very important for the maintenance and survival of the PPI network.<br />　In Chapter 4, I concluded that the evolutionary rates of the proteins in the PPI networks were strongly influenced by their PPI partners. Thus, it is reasonable to state that the evolutionary features of proteins in the PPI networks have been well reflected by their biological characteristics and functions of their PPI partners. Finally, I emphasized that evolutionary considerations of the PPI proteins were very important for understanding the building up of the current PPI networks., 総研大甲第869号},
 title = {Evolution of protein-protein interaction network},
 year = {}
}