{"created":"2023-06-20T13:21:06.636177+00:00","id":1205,"links":{},"metadata":{"_buckets":{"deposit":"5ce088a2-67e0-4de7-8fea-0c3be5867678"},"_deposit":{"created_by":1,"id":"1205","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"1205"},"status":"published"},"_oai":{"id":"oai:ir.soken.ac.jp:00001205","sets":["2:431:23"]},"author_link":["10193","10191","10192"],"item_1_creator_2":{"attribute_name":"著者名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"岩瀬, 峰代"}],"nameIdentifiers":[{}]}]},"item_1_creator_3":{"attribute_name":"フリガナ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"イワセ, ミネヨ"}],"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":"Humans and other mammals have a chromosomal system of sex determination.  Although the X and Y are quite different in size and gene content, they do share some homologous genes.  Nineteen X-Y homologous geme pairs could be categorized into four distinct groups (strata 1 to 4) based on the extent of synonymous sequence divergence (ks).  The mammalian amelogenin (AMEL) genes are shared by X and Y chromosomes.  They are gametologous and are designated as AMELX and AMELV respectively.  It is also known that the human AMELX is located near the boundary between strata 3 and 4.<br />  I confirmed that both AMELX and AMELY are single copy genes in non-human primates and located on the X and Y chromosome, respectively, by using fluorescence in situ hybridization (FISH).  Furthermore, I compared 20 kb human BAC clones that encompass the AMELX and AMELY loci.  I found that although the downstream region from intron 2 exhibits about 10 % sequence differences per site (p-distance), the upstream region exhibits higher level (p > 20%).  This observation suggests that the human AMELs span the boundary of strata 3 and 4.  I determined the genomic sequences of AMELs in five primates, two Artiodactyla and one Perissodactyla to examine their boundary region.  Comparisons of these genomic AMEL sequences reveal that the p-distances (the numbers of nucleotide differences per site) are significantly greater in the 5' portion from intron 2 than those in the 3' portion.  The observation is the same as that in the case of the human AMELs.  Furthermore, the phylogenetic analysis of gametologous AMELS shows their contrasting clustering patterns in different regions.  I therefore concluded that the boundary between strata 3 and 4 in the mammalian X chromosome also lies within AMEL intron 2.<br />  To investigate causes and mechanisms of creating evolutionary strata, I examined the human X and Y chromosome sequences which encompass strata 3 and 4 as well as the pseudoautosomal region 1 (PAR1).  To this end, I retrieved the sequences of the short arm of the human X chromosome (22 Mb) and aligned them with the Y homologous sequences.  Because of extensive sequence changes in the Y chromosome, l could align only one fifth (544 Kb) of the total X chromosome sequences.  It turned out that the X chromosome sequences could be divided into eleven segments (region I to XI) that ranges from the PAR1 to the region containing ZFX in stratum 3 on the X chromosome.  These eleven segments correspond to fourteen segments dispersed on the Y chromosome.  For each of these homologous regions, I examined the pattern and degree of nucleotide differences.  Results revealed that the p-distances are <0.1% in the PAR1 and increase abruptly to 10% in the middle of the XG locus that encompasses the pseudoautosomal boundary 1 (PAB1).  The p-distances remain around 10% in region II through the distal part of region IX, and then abruptly increase again to >20% at intron 2 of AMEL and in regions X and XI in stratum 3.<br />  To elucidate any features common to the PAB1 and the boundary between strata 3 and 4, I investigated if there are any sequence motifs that are shared by these boundaries.  To this end, I analyzed the above eleven X chromosome segments in terms of GC content, AT and GC skews, and the resolution sequences for Holliday intermediates.  Although in both regions I and IX, the p-distances increase sharply, no common sequence motifs were found.  It therefore seems difficult to attribute these sequence motifs or the primary nucleotide sequence in formation to any signal for the formation of stratum boundaries.<br />  Based on these results, I discussed the dating of sex chromosome differentiation, the roles of chromosomal inversion, the origin of evolutionary strata on the human sex chromosomes, and the tight linkages of male-determining genes as causes of the recombination suppression.  To date the emergence of strata 3 and 4, Jukes-Cantor distances (d-distances) were used to reconstruct the NJ tree.  I estimated that the emergence of stratum 3 occurred at 88-117 million years ago (mya) based on AMELX and 76-102 mya based on AMELY.  It therefore appeared that the mammalian AMELXs and AMELYs began to differentiate from each other almost immediately after they were translocated from an autosomal region.  The boundary spanning the AMEL locus is an ancient PAB and was formed in the stem lineage of ancestral mammals.  Furthermore, FISH results indicated that both X and Y chromosomal rearrangements have also occurred in the primate lineage.  Moreover, it was apparent that the order of eleven human X chromosomal regions is substantially different from that of fourteen human Y chromosomal regions.  Nevertheless, there were several evidences suggesting that inversions could not be a cause of strata.<br />  On the other hand, for the stratum 4 differentiation, I showed that genes or regions containing PART are different from species to species.  Those genes straddle evolutionary strata 4 and PART.  It thus seems that the PART was determined independently in diverse mammalian lineages.  This relatively recent and independent emergence of stratum 4 is reflected in a wide range of sequence divergences (8 to 15 %) exhibited in AMEL 3' region.  In fact, I came to the conclusion that the emergence of stratum 4 initiated 27～70 mya, depending on different mammalian lineages.<br />  I have found that the ancient PAB between strata 3 and 4 is the same among different mammals and interpreted this finding as the common ancestry of stratum 3.  In other words, it was formed in the common ancestor of eutherian mammals.  On the other hand, the present PAB was determined independently in diverse mammals.  I therefore argued that both ancient and present PABs were determined by chance events during the evolution of mammals and primates.<br />  However, I have failed to find molecular mechanisms that were responsible for stepwise suppression of homologous recombination in the mammalian sex chromosomes.  It is likely that the suppression was caused by some mechanisms working at the higher level than at the molecular level.  Population genetics theory suggested that one such cause is the necessity of tight linkage between male-determining genes on the Y chromosome.","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707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":"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":"2002"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"IWASE, Mineyo","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707_要旨.pdf","filesize":[{"value":"386.5 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/1205/files/甲707_要旨.pdf"},"version_id":"c81018f9-b062-46bc-ba34-8c74a2bcd9cd"}]},"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":"The tempo and mode of mammalian sex chromosome evolution","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"The tempo and mode of mammalian sex chromosome evolution"},{"subitem_title":"The tempo and mode of mammalian sex chromosome evolution","subitem_title_language":"en"}]},"item_type_id":"1","owner":"1","path":["23"],"pubdate":{"attribute_name":"公開日","attribute_value":"2010-02-22"},"publish_date":"2010-02-22","publish_status":"0","recid":"1205","relation_version_is_last":true,"title":["The tempo and mode of mammalian sex chromosome evolution"],"weko_creator_id":"1","weko_shared_id":1},"updated":"2023-06-20T14:39:44.827314+00:00"}