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内容記述 |
A variety of biological molecules play important roles in maintaining life through their intermingling networks. Among the networks is the metabolic one that functions as the interactions between substrates and enzymes. In other words, the metabolic network is composed of the enzymatic reactions (ERs) in which one or more enzymes catalyze the reactions of the pertinent substrates. Since metabolism is indispensable for maintaining life in all organisms, any changes of the metabolic networks must have greatly affected the organismic evolution.<br /> In his thesis, Tsuyoshi Tanaka has studied the evolution of the metabolic networks using the complete genome sequences and genealogical relationships among a number of species, both eukaryotes and prokaryotes. Based on the complete gene sets of the species studied, he examined whether a particular gene encoding the corresponding enzyme existed in the species in question. In particular, he conducted a comparative analysis of the metabolic networks among the species using the set of genes. First, he investigated the evolutionary process of the metabolic networks focusing on the gain and loss of ERs, because a single gene often functioned in more than one ER in the metabolic networks. Next, taking the pathways of vitamin B<SUB>6</SUB> (VB6) metabolism as an example, he systematically estimated the gain and loss of the genes during evolution of the species in order to elucidate the evolutionary process of the metabolic networks. In this examination, he used genes instead of ERs because he was able to identify directly the genes encoding for particular enzymes that were involved with the corresponding ERs in the pathways of VB6 metabolism.<br /> In Chapter 1, he has given an overview of his evolutionary study of the metabolic networks using the complete genome sequences. He has also described the motivation and purposes of the present study.<br /> In Chapter 2, he conducted comparative studies of ERs in the metabolic networks among the 6 eukaryotic species whose complete genome sequences were determined. For prokaryotes, it has been known that many gene losses had occurred during evolution. For eukaryotes, however, the evolutionary events of the gain and loss of genes in the metabolic networks are unknown, because no systematic studies have been conducted. The aim of this chapter is to examine how often gains and losses of enzymatic reactions (ERs) have occurred during the evolution of metabolic networks in eukaryotes, and how these evolutionary events have affected phenotypic traits of the organisms.<br /> As a result, he found that the losses of ERs had occurred more frequently than the gains during the evolutionary diversification of metabolic networks in different lineages of eukaryotic species. However, the vertebrate lineage after the separation from Drosophila melanogaster showed a remarkable increase in the number of ER gains compared with that of ER losses. In particular, 41% of ER gains were deeply involved with the lipid and complex lipid metabolisms. Because some products of these two metabolisms function as hormones, he concluded that ER gains of the two metabolisms accelerated the development of hormonal signal transduction for the elaborated regulation of physiological system during the vertebrate evolution.<br /> In Chapter 3, in order to understand the evolutionary process of the metabolic networks more detail, he focused upon the VB6 metabolism as an example. The group of VB6, particularly pyridoxal 5’- phosphate (PLP), functions as a cofactor of diverse enzymes in the amino acid metabolism. Most unicellular organisms and plants can biosynthesize PLP using any one of the three known PLP biosynthetic pathways; the de novo pathway, the salvage pathway and the fungi-type pathway. On the other hand, animals such as insects and mammals have to take it as nourishment, because they are deficient in the VB6 metabolism.<br /> To understand the evolutionary diversification and breakdown of the VB6 metabolism from the viewpoint of gain and loss of the genes, he conducted a comparative analysis of the sets of the genes involved in the VB6 metabolism among 122 species, including prokaryotes whose genome sequences were completely determined. In this study, he discussed the gain and loss of the 10 pertinent genes instead of ERs. As a result, he found that every one of the 10 genes was lost more than once in the evolutionary lineages of the 122 species.<br /> He has also made the following three findings in the evolution of VB6 biosynthesis: (1) A breakdown of the fungi-type pathway occurred at least three times independently in some of animal lineages, (2) the de novo pathway was established by generation of pdxB gene in gamma-proteobacteria, and (3) a fixed order of gene losses in the PLP biosynthetic pathways was evolutionarily conserved among lineages of the different species. These findings strongly suggest that an evolutionary process of the vitamin B<SUB>6</SUB> metabolism had remarkably been dynamic through the events of gain and loss of the genes during the evolution of the 122 species.<br /> Finally, in Chapter 4, Tsuyoshi Tanaka described the conclusions of his study. In particular, he came to the conclusion that the study of the gain and loss of ERs provided us with profound insight into the understanding of the evolutionary process of metabolic networks. Moreover, he concluded that the gain and loss of ERs not only played important roles in evolutionary diversification of the metabolic networks, but also greatly affected the whole evolutionary process from prokaryotes to eukaryotes. |
要旨・審査要旨 / Abstract, Screening Result (390.5 kB)
