{"_buckets": {"deposit": "5acf9695-2aef-4cca-99ca-dfa0be872306"}, "_deposit": {"created_by": 1, "id": "1223", "owners": [1], "pid": {"revision_id": 0, "type": "depid", "value": "1223"}, "status": "published"}, "_oai": {"id": "oai:ir.soken.ac.jp:00001223", "sets": ["23"]}, "author_link": ["0", "0", "0"], "item_1_biblio_info_21": {"attribute_name": "書誌情報（ソート用）", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2007-03-23", "bibliographicIssueDateType": "Issued"}, "bibliographic_titles": [{}]}]}, "item_1_creator_2": {"attribute_name": "著者名", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "金子, 聡子"}], "nameIdentifiers": [{"nameIdentifier": "0", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_creator_3": {"attribute_name": "フリガナ", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "カネコ, サトコ"}], "nameIdentifiers": [{"nameIdentifier": "0", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_date_granted_11": {"attribute_name": "学位授与年月日", "attribute_value_mlt": [{"subitem_dategranted": "2007-03-23"}]}, "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_1": {"attribute_name": "ID", "attribute_value_mlt": [{"subitem_description": "2007062", "subitem_description_type": "Other"}]}, "item_1_description_12": {"attribute_name": "要旨", "attribute_value_mlt": [{"subitem_description": "Processed pseudogenes are produced from the reverse transcription of mRNA followed\u003cbr /\u003eby integration into the genome. This process is mediated by enzymes encoded by \u003cbr /\u003eretrotransposable elements such as LINE-1 in mammals. In most cases, processed \u003cbr /\u003epseudogenes can not produce transcripts because of lacking functional promoter. \u003cbr /\u003eTherefore, processed pseudogenes are treated as genomic `fossil records\u0027. However, \u003cbr /\u003erecently, processed pseudogene has been shown to carry out biochemical function. In\u003cbr /\u003e mice, the \u003ci\u003eMakorinl-pl\u003c/i\u003e processed pseudogene regulates the mRNA stability of its\u003cbr /\u003e homologous coding gene (\u003ci\u003eMakorin 1\u003c/i\u003e) by competitive interaction for degradation\u003cbr /\u003efactors. In this thesis, molecular evolutionary and population genetics approaches are\u003cbr /\u003eused to investigate the  origin and evolution of \u003ci\u003eMakorin 1\u003c/i\u003e-derived processed\u003cbr /\u003epseudogenes. \u003cbr /\u003e　　　　　It is shown that \u003ci\u003eMakorin 1-p1\u003c/i\u003e originated almost immediately before the\u003cbr /\u003e\u003ci\u003emusculus\u003c/i\u003e and \u003ci\u003ecervicolor\u003c/i\u003e species groups diverged from each other some 4 mi11ion years ago and that the \u003ci\u003eMakorinl-pl\u003c/i\u003e orthologs in various Mus species are transcribed. \u003cbr /\u003eHowever,\u003ci\u003eMus caroli\u003c/i\u003e in the \u003ci\u003ecervicolor\u003c/i\u003e species group transcribes not only \u003ci\u003eMakorinl-pl,\u003c/i\u003e\u003cbr /\u003ebut also another older \u003ci\u003eMakorinl\u003c/i\u003e-derived processed pseudogene, demonstrating the\u003cbr /\u003erapid generation and turnover of the pseudogenes in the subgenus \u003ci\u003eMus\u003c/i\u003e. Under this\u003cbr /\u003ecircumstance, transcribed processed pseudogenes of \u003ci\u003eMakorin1\u003c/i\u003e evolve in a strictly\u003cbr /\u003eneutral fashion even with an enchanced substitution rate at CpG dinucleotide sites.\u003cbr /\u003e\u003ci\u003eMakorin1-pl\u003c/i\u003e is divided into three regions by its function and the homology to\u003cbr /\u003e\u003ci\u003eMakorin1\u003c/i\u003e; region A has no homology with \u003ci\u003eMakorin1\u003c/i\u003e, region B has homology with\u003cbr /\u003e\u003ci\u003eMakorin1\u003c/i\u003e and includes the target region of degradation factors, and region C has\u003cbr /\u003ehomology with \u003ci\u003eMakorin1\u003c/i\u003e but has no relationship with its mRNA stability. In mouse\u003cbr /\u003e\u003ci\u003eMakorin1-p1\u003c/i\u003eorthologs, there is no difference at the nucleotide substitution rate\u003cbr /\u003ebetween regions. \u003cbr /\u003e　　　　　Extended analyses of \u003ci\u003eMakorin1\u003c/i\u003e-derived processed pseudogenes in the genome \u003cbr /\u003edatabase and genomic PCRs show that rats have their own \u003ci\u003eMakorin1\u003c/i\u003e-derived\u003cbr /\u003eprocessed pseudogene. Furthermore, RT-PCRs using testis tota1 RNA demonstrate the\u003cbr /\u003ecotranscription of \u003ci\u003eMakorin1\u003c/i\u003e and \u003ci\u003eMakorinl\u003c/i\u003e-derived processed pseudogenes in rats.\u003cbr /\u003eThese results suggest that the rat  specific \u003ci\u003eMakorin1\u003c/i\u003e-derived processed pseudogene can take over the role of \u003ci\u003eMakorin1-p1\u003c/i\u003e in the subgenus \u003ci\u003eMus.\u003c/i\u003e Extended analyses to other\u003cbr /\u003emammals (dogs, cows, chimpanzees and humans) using genome databases also shows that each species has its own \u003ci\u003eMakorin1\u003c/i\u003e-derived processed pseudogenes, except for chimpanzees and humans. In dogs, they  have three relatively recently originated \u003ci\u003eMakorin1\u003c/i\u003e-derived processed pseudogenes, suggesting that \u003ci\u003eMakorin1\u003c/i\u003e-derived processed pseudogenes are rapidly generated in dogs as in mice. Thus, there is a possibility that \u003ci\u003eMakorin1\u003c/i\u003e mRNA stability has been maintained by its processed pseudogenes in dogs. In cows, chimpanzees and humans, however, relatively recent \u003ci\u003eMakorin1\u003c/i\u003e-derived processed pseudogenes do not exist. In cows, due to incompleteness of the genome database, such newly emerged sequences may not be identified. In humans and chimpanzees, seven\u003ci\u003eMakorin1\u003c/i\u003e-derived processed pseudogenes exist, and all of them show the relatively old origin. For stability of \u003ci\u003eMakorin1\u003c/i\u003emRNA, the impormt featue is sequence similarity and transcription. RT-PCRs using testis total RNA demonstrate the cotranscription of \u003ci\u003eMakorin1\u003c/i\u003e and \u003ci\u003eMakorin1\u003c/i\u003e-derived processed pseudogenes in humans too. If humans and chimpanzees do not have relatively recent \u003ci\u003eMakorin1\u003c/i\u003e-derived processed pseudogenes, preexisting pseudogenes must be prevented from accumulating detrimental mutations by negative selection on functionally related region (B region). In fact, comparison between human and chimpanzee orthologs reveals that the B region in two \u003ci\u003eMakorin1\u003c/i\u003e-derived processed pseudogenes,\u003ci\u003eMKRN4\u003c/i\u003e and \u003ci\u003eMKRNP1\u003c/i\u003e, isconserved. \u003cbr /\u003e　　　　　To examine whether this conservation is general in primale lineage and human populations, extended analyses to simian primates and human populations using genomic PCRs and genome database searches were carried out. Prosimians have their own specific \u003ci\u003eMakorin1\u003c/i\u003e-derived processed pseudogenes. \u003ci\u003eGalagoides demidoff\u003c/i\u003e\u003cbr /\u003e(Demidoff’s galago) has one \u003ci\u003eMakorinl\u003c/i\u003e-derived processed pseudogene which has high\u003cbr /\u003e homology with \u003ci\u003eMakorin1\u003c/i\u003e in humans and mice, while \u003ci\u003eGalago moholi\u003c/i\u003e(South African\u003cbr /\u003egalago) and \u003ci\u003eOtolemur  crassieaudatus\u003c/i\u003e(thick-tailed bush baby) have two pairs of\u003cbr /\u003eorthlogous \u003ci\u003eMakorin1\u003c/i\u003e-derived processed pseudogenes and one of them indicates the\u003cbr /\u003econservation of the B region. New World monkeys and Catarrhini have orthologous\u003cbr /\u003epairs of human Makorin1-derived processed pseudogenes. Unlike rodents,\u003cbr /\u003e\u003ci\u003eMakorin1\u003c/i\u003e-derived processed pseudogenes occur rather infrequently in simian primates.\u003cbr /\u003eUnder this circumstance, it is hypothesized that preexisting transcribed processed\u003cbr /\u003epseudogenes must be prevented from accumulating detrimental mutations by negative\u003cbr /\u003eselection. Comparison of \u003ci\u003eMKRN4\u003c/i\u003eorthologous pairs shows that the conservation of the\u003cbr /\u003eB region is limited to humans and chimpanzees.　In contrast to \u003ci\u003eMKRN4\u003c/i\u003e, comparison of\u003cbr /\u003e\u003ci\u003eMKRNP1\u003c/i\u003e orthlogous pairs shows that the conservation of the B region is general, and\u003cbr /\u003eespecially, the strict conservation is observed in hominoids. In human populations,\u003cbr /\u003e both \u003ci\u003eMKRN4\u003c/i\u003e and \u003ci\u003eMKRNPI1\u003c/i\u003eshow the reduction of the nucleotide diversity in the B\u003cbr /\u003e region, compared with other region. \u003cbr /\u003e　　　　　From the above observation it is concluded as follows: 1) The transcription of\u003cbr /\u003e\u003ci\u003eMakorinl\u003c/i\u003e-derived processed pseudogene is not limited to mice. The phenomenon is\u003cbr /\u003erather general in mammals. 2) The rate of emergence of these pseudogenes is, however, different from species to species. And 3) The evolutionary rate and pattern of\u003cbr /\u003e\u003ci\u003eMakorin1\u003c/i\u003e-derived processed pseudogenes depend heavily on how frequently they are\u003cbr /\u003edisseminated in the genome.", "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1077号", "subitem_description_type": "Other"}]}, "item_1_select_14": {"attribute_name": "所蔵", "attribute_value_mlt": [{"subitem_select_item": "有"}]}, "item_1_select_16": {"attribute_name": "複写", "attribute_value_mlt": [{"subitem_select_item": "印刷物から複写可"}]}, "item_1_select_17": {"attribute_name": "公開状況", "attribute_value_mlt": [{"subitem_select_item": "要旨のみ公開"}]}, "item_1_select_8": {"attribute_name": "研究科", "attribute_value_mlt": [{"subitem_select_item": "先導科学研究科"}]}, "item_1_select_9": {"attribute_name": "専攻", "attribute_value_mlt": [{"subitem_select_item": "21 生命体科学専攻"}]}, "item_1_text_10": {"attribute_name": "学位授与年度", "attribute_value_mlt": [{"subitem_text_value": "2006"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "KANEKO, Satoko", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "0", "nameIdentifierScheme": "WEKO"}]}]}, "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", "download_preview_message": "", "file_order": 0, "filename": "甲1077_要旨.pdf", "filesize": [{"value": "371.5 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_11", "mimetype": "application/pdf", "size": 371500.0, "url": {"label": "要旨・審査要旨", "url": "https://ir.soken.ac.jp/record/1223/files/甲1077_要旨.pdf"}, "version_id": "c45524db-670d-4654-9797-a5238a8858c0"}]}, "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": "Molecular Evolutionary and Population Genetics Studies on Regulatory Makorin1-derived Processed Pseudogenes", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Molecular Evolutionary and Population Genetics Studies on Regulatory Makorin1-derived Processed Pseudogenes"}, {"subitem_title": "Molecular Evolutionary and Population Genetics Studies on Regulatory Makorin1-derived Processed Pseudogenes", "subitem_title_language": "en"}]}, "item_type_id": "1", "owner": "1", "path": ["23"], "permalink_uri": "https://ir.soken.ac.jp/records/1223", "pubdate": {"attribute_name": "公開日", "attribute_value": "2010-02-22"}, "publish_date": "2010-02-22", "publish_status": "0", "recid": "1223", "relation": {}, "relation_version_is_last": true, "title": ["Molecular Evolutionary and Population Genetics Studies on Regulatory Makorin1-derived Processed Pseudogenes"], "weko_shared_id": 1}