{"_buckets": {"deposit": "47cc9f78-05dd-443e-9917-48529fc74088"}, "_deposit": {"created_by": 21, "id": "2713", "owners": [21], "pid": {"revision_id": 0, "type": "depid", "value": "2713"}, "status": "published"}, "_oai": {"id": "oai:ir.soken.ac.jp:00002713", "sets": ["25"]}, "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": "2011-09-30", "bibliographicIssueDateType": "Issued"}, "bibliographic_titles": [{}]}]}, "item_1_creator_2": {"attribute_name": "著者名", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "桂, 有加子"}], "nameIdentifiers": [{"nameIdentifier": "0", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_creator_3": {"attribute_name": "フリガナ", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "カツラ, ユカコ"}], "nameIdentifiers": [{"nameIdentifier": "0", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_date_granted_11": {"attribute_name": "学位授与年月日", "attribute_value_mlt": [{"subitem_dategranted": "2011-09-30"}]}, "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": "2011070", "subitem_description_type": "Other"}]}, "item_1_description_12": {"attribute_name": "要旨", "attribute_value_mlt": [{"subitem_description": "\u0026nbsp;\u0026nbsp;Sex determination is essential to the reproductive success of an individual in sexuallyreproducing species, but the system of sex determination has evolved variously amongorganisms. In most sexually reproducing species, the sex of an individual is determinedby combination of sex chromosomes. On the sex chromosome, different species havedifferent types of a sex-determining gene, which is the most primary factor for thegonadal differentiation. I conducted evolutionary genetics research on the emergenceand evolution of sex chromosomes and a primary sex-determination gene in mammalsto better understand the evolution of sex determination systems. In Chapter 1, Iprovided a general introduction to this study and described the aims of this research.\r\n\u0026nbsp;\u0026nbsp;In mammals, the sex-determining region Y (SRY) is a testis-determining geneon the Y chromosome. Chapter 2 described the molecular evolution of mammalianmale-determining SRY genes. By comparing marsupial and eutherian SRY genes, Iattempted to elucidate how SRY genes evolved and proposed a new scenario forexplaining how the specialized function of male determination developed independentlyin marsupials and eutherians. The results revealed that the functional differentiation ofthe marsupial SRY differed from that of the eutherian. The lineage-specific changes thathave been observed in the SRY and other sex determination-related genes (SOX9 andAd4BP/SF-1) implied that molecular coevolution of genes has occurred in the sexdetermination system of eutherians. \r\n\u0026nbsp;\u0026nbsp;In Chapter 3, I proposed how therian (marsupial and eutherian) sexchromosomes became differentiated. Essentially, the X and Y chromosomes of thesetaxa originated from a pair of autosomes, with this differentiation of sex chromosomesbeing attributable to the suppression of recombination. Although a previous hypothesisproposed that X and Y differentiation in therian ancestors arose through a two-stepprocess (called “evolutionary strata 1 and 2”; Lahn and Page, 1999), I posited that thisdifferentiation arose only once and the entire sex chromosome differentiatedsimultaneously in the therian ancestor. However gene conversion in eutherians reducedthe nucleotide divergence between some gametologs, which meant that they couldsubsequently be categorized as different strata. Based on these findings, I provided anew scenario to explain the differentiation of mammalian sex chromosomes byconsidering the effects of genomic rearrangements, such as a chromosomal inversion,on the sex chromosome.\r\n\u0026nbsp;\u0026nbsp;Chapter 4 clarified the genome structure and gene family on sexchromosomes. I focused on intrachromosomal segmental duplications (ISDs) thatproduce tandem and/or inverted repeats (\u003e50 kb) in neighboring regions; compared toother chromosomes, the X chromosomes of humans possess the highest number of theseISDs. Comparisons of mammalian sex chromosomes revealed that the pattern, numberand/or size of ISDs on the chromosomes differed among the examined species (human,mouse, opossum, and platypus). In particular, the characteristics of these structures inthe human and mouse X chromosome were shown to be considerably more complicatedthan those observed in the opossum and platypus. These findings implied that theseISDs accumulated extensively in the X chromosomes of therian ancestors. I thendiscussed that the complexity of these structures on the eutherian X chromosome mightbe correlated with the evolution of multigene families, such as cancer testis antigengenes (CTAs).\r\n\u0026nbsp;\u0026nbsp;In chapter 5, the molecular evolution and genome structure of the melanomaantigen gene (MAGE) family, which is one of CTAs and is located on the Xchromosome, was examined in primate genomes. I proposed that human-specificpalindromic sequences, including the MAGE-A genes, were conserved by negativeselection. Since the MAGE-A genes encode epitopes of cancer cells, the bindingcapacity of the epitopes to highly divergent human leukocyte antigen (HLA) moleculeswas preserved. This finding was interesting because it could be used to betterunderstand the significance of genomic structure on the X chromosome.\r\n\u0026nbsp;\u0026nbsp;Chapter 6 provided general discussion about the results presented in Chapters2 to 5, including sex determination systems in both mammalian and non-mammaliantaxa. In Chapter 7, all of the chapters were summarized and, based on all of the findingspresented, I provided a generalized description of evolution of sex determinationsystems, and described the biological significance of such a system having theapparently contradictory characteristics of evolutionary flexibility and stability. 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