{"created":"2023-06-20T13:20:54.815684+00:00","id":984,"links":{},"metadata":{"_buckets":{"deposit":"4a1cf093-8feb-4e85-a745-6189c9dc3415"},"_deposit":{"created_by":1,"id":"984","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"984"},"status":"published"},"_oai":{"id":"oai:ir.soken.ac.jp:00000984","sets":["2:430:20"]},"author_link":["10094","10092","10093"],"item_1_creator_2":{"attribute_name":"著者名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"花田, 耕介"}],"nameIdentifiers":[{}]}]},"item_1_creator_3":{"attribute_name":"フリガナ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"ハナダ, コウスケ"}],"nameIdentifiers":[{}]}]},"item_1_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2003-03-24"}]},"item_1_degree_grantor_5":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"総合研究大学院大学"}]}]},"item_1_degree_name_6":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(理学)"}]},"item_1_description_12":{"attribute_name":"要旨","attribute_value_mlt":[{"subitem_description":"It is known that many kinds of diseases are caused by viruses having RNA as their genetic materials. In general, RNA viruses evolve by evolutionary factors including mutation and selection. Selection against RNA viruses is mainly caused by the interaction with the host species, because RNA viruses can survive only as parasites of the host species. Therefore, it is of particular importance to investigate the interactions between RNA viruses and the host for studying the evolution of RNA viruses. In this thesis, l focused on the following three interacting features with the host; 1) modes of viral infection to the host, 2) viral adaptation to a single host and 3) exchanging genomic regions between RNA viruses and the host.
In chapter 1, first, I defined the virus as an organism that could survive and grow only in the living cell, and that contained a protein coat surrounding a nucleic acid core but having no semi permeable membrane. In addition to the definitions, I outlined the taxonomy and evolutionary mechanisms of RNA viruses.
In chapter 2, I estimated the rates of synonymous substitution for 46 species of RNA viruses and found a large amount of variation in the rates (the difference in the 3rd orders of magnitude). On the other hand, through constancy in the rate of replication error among RNA viruses examined, I concluded that the main factor for the variation of the substitution rates was the differences in the replication frequency. This is because we can assume that the rate of synonymous substitution is determined by the rate of replication error and the replication frequency. Moreover, I examined relationships between the rates of synonymous substitution and several modes of viral infections to the host including the transmission modes. The results obtained indicate that the rate of synonymous substitution was strongly related to the difference in the modes of viral infection to the host. The reason was speculated as that the modes of viral infection to the host altered the replication frequency.
In chapter 3, using porcine reproductive and respiratory syndrome virus(PRRSV) whose synonymous substitution rate was the highest among the 46 species of RNA viruses, I conducted evolutionary analyses in order to understand the evolutionary process of PRRSV. The virus is a recently emerged pathogen in domesticated swines. Epidemiological data suggest that the divergence time of PRRSV is about 15 years ago. For confirming the rapidness of the synonymous substitution rate in PRRSV, I first estimated the divergence time of PRRSV by molecular evolutionary analysis, and compared it with that inferred from the epidemiological data. As a result, the divergence time estimated by the evolutionary analysis well corresponded to that estimated by the epidemiological data. This correspondence ensured the rapidness of the rate in PRRSV Second, I studied the envelope regions as an important element for viral adaptation to the host. In particular, positively selected sites were detected in the envelope gene by my computer analysis. Interestingly, the sites were located not only in the regions attacked by the host immune system but also in the transmembrane regions including a signal peptide. The positively selected sites in the transmembrane regions were considered to be irrelevant for escaping the immune system, because no amino acid substitutions were observed in the transmembrane regions of the sequences isolated from piglets that were experimentally infected by PRRSV. In other words, the transmembrane regions and the signal peptide are thought to be specific to a given membrane. Therefore, l think that the positively selected sites of the membrane regions are important not for the viral adaptation to the host immune system but for the viral attachment to the membrane of the new host cell, because PRRSV emerged recently as mentioned above.
In chapter 4, I searched for eukaryotic genomic regions homologous to RNA viruses to find how often the exchange of a genomic sequence has occurred between RNA viruses including retro and non-retro viruses and 6 eukaryotic genomes such as Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, and Saccharomyces cerevisiae. The evolutionary origin of the homologous regions was studied by phylogenetic analysis.
For the non-retrovirus RNA viruses, I obtained two major results: First, a part of the Borna virus genome (nucleocapsid protein gene) was shown for the first time to be derived from mammalian genomes. Second, the 6 eukaryotic genomes did not have any part of the virus genome.
In the case of the retroviruses and the two mammalian species, Homo sapiens and Mus musculus, I obtained four results. First, retrovirus-like regions occupied about 0.1% of each of the whole genomes of the two species. Second, physical maps indicating the locations of the retrovirus-like regions were constructed for both genomes. Third, the retrovirus-like regions were not randomly distributed in both complete genomes at a significant level (P<0.01). Forth, there exists a positive correlation
between the GC content of retrovirus-like regions and that of the flanking regions for both species. From these results, I have concluded that retroviruses have been integrated into the host genome where the GC content was similar to each other.
The present study will give a insight not only into the evolutionary origin and process of RNA viruses but also the interacting features between RNA viruses and their hosts.","subitem_description_type":"Other"}]},"item_1_description_18":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_1_description_7":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"総研大甲第684号","subitem_description_type":"Other"}]},"item_1_select_14":{"attribute_name":"所蔵","attribute_value_mlt":[{"subitem_select_item":"有"}]},"item_1_select_8":{"attribute_name":"研究科","attribute_value_mlt":[{"subitem_select_item":"生命科学研究科"}]},"item_1_select_9":{"attribute_name":"専攻","attribute_value_mlt":[{"subitem_select_item":"18 遺伝学専攻"}]},"item_1_text_10":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_text_value":"2002"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"HANADA, Kousuke","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲684_要旨.pdf","filesize":[{"value":"307.4 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"要旨・審査要旨 / Abstract, Screening Result","url":"https://ir.soken.ac.jp/record/984/files/甲684_要旨.pdf"},"version_id":"dfa390e6-82ac-49fa-986d-95e6342313e3"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲684_本文.pdf","filesize":[{"value":"4.1 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"本文","url":"https://ir.soken.ac.jp/record/984/files/甲684_本文.pdf"},"version_id":"7703bde3-6c19-4cdc-9cca-0aab53631ab0"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"Evolutionary features of RNA viruses with special reference to mutation rates and transmission modes","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Evolutionary features of RNA viruses with special reference to mutation rates and transmission modes"},{"subitem_title":"Evolutionary features of RNA viruses with special reference to mutation rates and transmission modes","subitem_title_language":"en"}]},"item_type_id":"1","owner":"1","path":["20"],"pubdate":{"attribute_name":"公開日","attribute_value":"2010-02-22"},"publish_date":"2010-02-22","publish_status":"0","recid":"984","relation_version_is_last":true,"title":["Evolutionary features of RNA viruses with special reference to mutation rates and transmission modes"],"weko_creator_id":"1","weko_shared_id":1},"updated":"2023-06-20T14:40:44.384547+00:00"}