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内容記述 |
It is believed that primordial eukaryotes were derived from prokaryotes, acquiring<br />nucleus. A number of attempts have been made to reveal the early evolution of<br />eukaryotes, and some hypotheses for the emergence of the early eukaryotes are<br />proposed so far. However, the evolutionary process of early eukaryotes is still a<br />controversial issue and remains one of the biggest questions in current biology. In this<br />study, with the eventual goal toward elucidation of the evolutionary origin and process<br />of early eukaryotes, I conducted molecular evolutionary analyses of transporter proteins<br />of ribosomes between the nucleus and the cytoplasm, called ribosome export factors<br />(REFs).<br /> This thesis consists of four chapters and an appendix. In <b>Chapter 1</b>, I described the<br />research background for this study, with particular emphasis on the molecular function<br />of the REFs. The ribosome, one of the largest complexes in eukaryotic cells, is to be<br />exported from the nucleus to the cytoplasm through nuclear pores. As discovered in<br />recent years, the kinetic steps in this nucleocytoplasmic transport pathway are<br />stimulated by the REFs. The REFs would be worth focusing on because they can be<br />considered as one of the components in the eukaryotic core system, translation, and as<br />one of the key genes in the evolutionary process of early eukaryotes for maintaining the<br />mobility of the ribosomes under the existence of nuclear membrane in the<br />then-emerging eukaryotic cells. <br /> In <b>Chapter 2</b>, with the aim of revealing the functional significance of the REFs in<br />the process of eukaryotic evolution, I examined the functional constraints of the entire<br />translation system, the ribosomal proteins and the REF proteins. Estimating the relative<br />evolutionary rates of the yeast REF proteins, I found that, although not as much as the<br />ribosomal proteins, the REF proteins do slowly evolve. More interestingly, the<br />evolutionary rates of the REFs can be classified into two groups. In order to explain this<br />difference in evolutionary rates between the two groups, I considered two subcategories<br />for the REFs, according to the steps in which the REFs are involved. Those two<br />subcategories are non-membranous REFs (non-mREFs) and membranous REFs<br />(mREFs). Interestingly, this categorization was coincided with the evolutionary rate<br />difference: Namely, the rapidly evolving REFs were the non-mREFs while the slowly<br />evolving REFs were the mREFs. These results show that the mREF proteins evolve<br />slower than the non-mREF proteins, suggesting the functional importance of mREFs in<br />the evolutionary process of eukaryotes. <br /> In <b>Chapter 3</b>, I examined the evolutionary origin of the eukaryotic nucleus by<br />conducting the ortholog detection analysis of the REFs in prokaryotic lineages. The<br />evolutionary origin of the nucleus is still unclear, although a number of hypotheses have<br />been proposed so far. I searched for the origin of the REFs in archaeal and eubacterial<br />lineages by the method of PSI-BLAST. The results obtained showed that the<br />non-mREFs originated exclusively from eubacterial proteins whereas the mREFs were<br />from both archaeal and eubacterial proteins. Thus, the REFs working inside the nuclear<br />membrane (<i>i.e.</i>non-mREFs) are derived only from eubacteria, while alternatively, the<br />REFs shuttling between the nucleus and the cytoplasm (<i>i.e.</i> mREFs) are from both<br />archaea and eubacteria. If we assume that the early nucleus has parsimoniously<br />employed intranuclear proteins as the intranuclear transporters (<i>i.e.</i> non-mREFs), these<br />data suggest that the structure of the nucleus may be a descendant of the eubacterial cell. <br />At least, it is suggested that the nucleus arose in a cell that contained chromosomes<br />possessing a substantial fraction of eubacterial genes. Therefore, from the viewpoint of<br />ribosome transport, it is plausible that the nuclear structure is not originated from<br />archaea, but from eubacteria. <br /> Lastly, in <b>Chapter 4</b>,I provided a summary and conclusions for the present study. I<br />have shown that the REFs evolve slowly, in addition, the mREFs evolve more slowly, <br />suggesting that the entire eukaryotic translation system is under the functional<br />constraints, and in particular, that the mREFs are functionally important in the process<br />of eukaryotic evolution. Moreover, from the prokaryotic origin of the REFs, it is<br />suggested that the nucleus is rather a descendant of the eubacterial cell, not the archaeal cell. <br /> In <b>Appendix</b>, I made particular mention to the biological database projects for<br />eukaryotes, in which I have been involved. Comprehensive annotations of model<br />eukaryotes and integrated databases for such annotations are becoming more and more important in the current post-genome era. Moreover, such databases are useful for the study of early evolution of eukaryotes that is the main aim of the present study. Such<br />databases are also invaluable for comprehensive access to the information resources, <br />and will stimulate the comparative evolutionary genomics. With the eventual goal to<br />know the early evolution of eukaryotes, here I refer to three eukaryotic database projects<br />in which I have been involved, <u>the Molecular Database of <i>Hydra</i> Cells</u>, <u>the Rice<br />Annotation Project Database (RAP-DB)</u>, and <u>the H-Invitational Database (H-InvDB)</u>. <br /> The Molecular Database of <i>Hydra</i> Cells includes the invaluable data of expression<br />patterns of cell type-specific genes in <i>Hydra</i>, a member of phylum Cnidaria, which<br />branched more than 500 million years ago from the main stem leading to all bilaterian<br />animals. The database framework was developed by myself, and it serves a unique<br />opportunity for graphically browsing more than 100 cell type-specific genes in <i>Hydra.</i> <br />All of the resources can be accessed through http://hydra.lab.nig.ac.jp/hydra/.<br /> The RAP-DB is a database for <i>Oryza sativa</i> ssp. <i>Japonica</i>, one of the model<br />eukaryotes, and has been developed in order to comprehensively house all the<br />annotations produced by the RAP (Rice Annotation Project), which is internationally<br />organized with the aim of providing standardized and highly accurate annotations of the<br />rice genome. The latest version of the RAP-DB contains 3l,439 genes validated by<br />cDNAs. The RAP-DB has been also developed by myself, and employed in the analyses<br />within <b>Chapter 2</b>. The RAP-DB is available at http://rapdb.lab.nig.ac.jp/.<br /> The H-Invitational Database (H-InvDB) was originally developed as an integrated<br />database of the human transcriptome that was based on extensive annotation of large<br />sets of full-length cDNA (FLcDNA) clone. I participated in the Annotation Meeting of<br />Genome Information Integration Project for the further development of the human<br />genome annotations. Now, the database provides annotation for 175,537 human<br />transcripts and 120,558 human mRNAs extracted from the public DNA databank, in<br />addition to 54,978 human FLcDNA, in the latest release, H-InvDB_4.3. The H-InvDB<br />is available at http://www.h-invitational jp/.<br /> The three projects in which I have been involved produced comprehensive<br />information for the model eukaryotes. Each database provides a nice implementation for<br />each biological resource and will stimulate the further exploration in the early evolution<br />of eukaryotes. |
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