{"created":"2023-06-20T13:20:52.558141+00:00","id":938,"links":{},"metadata":{"_buckets":{"deposit":"922f92a1-2679-4159-92d0-40498571dc41"},"_deposit":{"created_by":1,"id":"938","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"938"},"status":"published"},"_oai":{"id":"oai:ir.soken.ac.jp:00000938","sets":["2:430:20"]},"author_link":["9970","9971","9969"],"item_1_creator_2":{"attribute_name":"著者名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"北野, 誉"}],"nameIdentifiers":[{}]}]},"item_1_creator_3":{"attribute_name":"フリガナ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"キタノ, タカシ"}],"nameIdentifiers":[{}]}]},"item_1_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"1999-03-24"}]},"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":"　　　Majority of the genes are evolving under the neutral mutation pressure. However, some genes are evolving through positive selection. Blood types were originally distinguished by the different molecular structure on erythrocytes. Therefore these products of blood group genes may cause interactions with other organisms, and there is possibility of positive selection on those genes. Because the Rh blood group gene products are membrane proteins, these products of blood group genes seemed to be affected by interactions with other organisms or cells on surface regions. It is known that the Rh blood group genes have homologous genes named Rh50, and hominoids have two or three Rh blood group genes. Therefore the Rh blood group genes and their related genes experienced a series of gene duplication events. Analyses of gene duplication events are also important to elucidate evolutionary rates and patterns of these genes. I thus analyzed the Rh blood group genes and their related genes from primates to fish to clarify the tempo and mode of evolution of these genes.<br />　　　The human Rh blood type is one of the major blood group systems, and plays important roles in transfusion and clinical medicine, including haemolytic diseases of newborns, autoimmune diseases, and mild haemolytic anemia. Landsteiner and Wiener detected an antibody that agglutinates blood cells from rhesus macaques, and it was named Rh. Nucleotide sequences of Rh blood group genes in some primates were reported, and the phylogenetic relationship of primate Rh blood group genes have been conducted. However, the phylogenetic relationship of primate Rh blood group genes from these studies is not compatible with each other. Because hominoids have two or three loci of Rh blood group genes by gene duplication, gene conversion events (or some kind of convergent effects) may prevent to determine the true gene tree.<br />　　　I examined the evolution of the Rh blood group genes of primates. Because we don't know the actual gene tree topology of primate Rh blood group genes, I assumed two plausible trees from nucleotide sequence data by using phylogenetic networks. I used the site by site reconstruction method under the maximum likelihood estimates to identify regions of gene conversion events assuming the two trees, and detected 9 or 11 converted regions. After eliminating the effect of gene conversions, I estimated numbers of nonsynonymous and synonymous substitutions for each branch of the both trees. Whichever we selected gene trees, the branch connecting hominoids and Old World monkeys showed significantly higher nonsynonymous than synonymous substitutions, that is, indication of positive selection by using a statistical test. Many other branches also showed higher nonsynonymous than synonymous substitutions, and this suggests that the Rh genes have experienced some kind of positive selection. In any case, we should be very careful when we analyse the evolutionary history of tandemly duplicated genes, for there is always possibility of gene conversions.<br />　　　To examine evolutionary patterns of other mammalian Rh blood group genes, I determined complete coding regions of Rh blood group genes of five mouse subspecies and rat, and Rh50 genes of five mouse subspecies, rat, and crab-eating macaque, and examined these genes. Nucleotide and amino acid sequence similarities between Rh genes and Rh50 genes are 47.2-48.9% and 34.4-37.8%, respectively. Comparison of synonymous and nonsynonymous substitutions for the Rh50 gene also revealed a possibility of existence of positive selection for this gene in primates. Because primates showed more clear sign of positive selection than rodents both for Rh and Rh50 genes, it is possible that the pattern of host-parasite interaction is different between primates and rodents. Phylogenetic analyses of Rh and Rh50 amino acid sequences indicate that the Rh50 gene has been evolving about two times more slowly than the Rh blood group gene both in primates and rodents. This conservative nature of the Rh50 gene suggests its relative importance to the Rh blood group gene. From the comparison of synonymous substitutions between Rh and Rh50 genes, it is suggested that the mutation rate of rodents is about three times higher than that of primates, and the divergence time between mouse and rat is estimated to be ca. 30 million years ago.<br />　　　I also determined the Rh50-like genes of Xenopus and Japanese medaka and examined the long-term evolution of Rh, Rh50, and their related genes. The phylogenetic tree shows four clusters in this tree; Rh50 genes of mammals and the Xenopus Rh50-like gene, Rh genes of mammals, the Rh50-like gene of Japanese medaka, and two genes of C. elegans. Therefore, the Xenopus Rh50-like gene is probably orthologous to the Rh50 genes of mammals.<br />　　　The topology of the phylogenetic tree suggests that the gene duplication of Rh and Rh50 genes occurred just before or after the divergence of teleost fish and other vertebrates. The branch lengths of Rh50 genes are much shorter than those of Rh genes, indicating a lower evolutionary rate in the Rh50 gene than in the Rh gene. Because its evolutionary rate is lower than that for the Rh protein gene, the Rh50 protein may be closer to the ancestral form before the gene duplication of Rh and Rh50 genes. The time of gene duplication that produced the Rh and Rh50 genes was estimated to be about 450-480 million years ago. This period roughly corresponds to the early Paleozoic, around the divergence between tetrapods and teleost fish lineages.<br />　　　From database searches, it is suggested that the Rh blood group genes and their related genes are related to ammonium transporter genes of many organisms, especially trans-membrane domains. The phylogenetic tree for ammonium transporter proteins indicated two major groups for ammonium transporter proteins. I propose to call these two groups of ammonium transporter genes as α and β groups, and the Rh genes group is more similar to the amt β group than to the amt α group. It is suggested that the Rh blood group genes and their related genes have probably been existing as essential membrane proteins in many animal phyla.","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403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":"1998"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"KITANO, Takashi","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403_要旨.pdf","filesize":[{"value":"334.3 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/938/files/甲403_要旨.pdf"},"version_id":"2cfc10a0-3ac6-40da-8e3d-f4705526bced"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲403_本文.pdf","filesize":[{"value":"16.1 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"本文","url":"https://ir.soken.ac.jp/record/938/files/甲403_本文.pdf"},"version_id":"907cf6e8-91c9-4bf5-8673-c88bcf4be199"}]},"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":"Evolution of the Rh Blood Group Genes andTheir Related Genes","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Evolution of the Rh Blood Group Genes andTheir Related Genes"},{"subitem_title":"Evolution of the Rh Blood Group Genes andTheir Related Genes","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":"938","relation_version_is_last":true,"title":["Evolution of the Rh Blood Group Genes andTheir Related Genes"],"weko_creator_id":"1","weko_shared_id":1},"updated":"2023-06-20T14:41:59.517739+00:00"}