{"created":"2023-06-20T13:20:54.298676+00:00","id":973,"links":{},"metadata":{"_buckets":{"deposit":"02590495-435d-4542-a96e-a24bb6df4cd2"},"_deposit":{"created_by":1,"id":"973","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"973"},"status":"published"},"_oai":{"id":"oai:ir.soken.ac.jp:00000973","sets":["2:430:20"]},"author_link":["10061","10060","10059"],"item_1_creator_2":{"attribute_name":"著者名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"峯田, 克彦"}],"nameIdentifiers":[{}]}]},"item_1_creator_3":{"attribute_name":"フリガナ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"ミネタ, カツヒコ"}],"nameIdentifiers":[{}]}]},"item_1_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2002-03-22"}]},"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":"The understanding of the evolutionary process of the central nervous system (CNS), in particular a brain, is one of the challenging tasks in modern biology. It is easily imaginable that biological complexity of the CNS is mainly due to not only structural complexity but also complicated and elaborated network of function. There is no doubt that functional network must be maintained by a network of multiple gene interaction that are intriguingly maintained by gene expression control. The extreme difficulty of studying the CNS might be due to a lack of definite approach to understand multiple interaction of gene expression. However, it is fortunate that the recent advancement of genome projects and cDNA projects provided us with the molecular biological methods for identifying gene sets and the degree of gene expression in a particular organ of a given species. When we define a gene expression profile as an occurrence frequency of the expressed gene species in a given organ, I thought that comparative studies of gene expression profiles in the CNS among various organisms might give profound insight into the understanding of evolutionary processes of the CNS. Here in my thesis, I proposed a novel approach for the evolutionary study of CNS, focusing on the gene expression profiles. Since an expression profile results from the transcriptional activities of all genes involved in the networks, the expression profile should reflect the outcome of transcriptional regulations of all genes expressed in a given organ. Thus, the purpose of my thesis is to answer the question whether the evolutionary process of CNSs can be understood from the gene expression profiles.
To attain the purpose, I examined the gene expression profiles at the following levels; (1) a conservation pattern of the nervous system-related genes, (2) the divergence of the gene expression profiles at the cell level, and (3) the divergence of the gene expression profiles at the level of the organs such as a brain. In particular, I examined if the correspondence is good between the species tree conventionally obtained and the tree of gene expression profile invented in my study.
This thesis is composed of five chapters. In chapter 1, 1 described the outline of the present thesis, placing particular emphasis on the motivation and purpose of my study. I also noted that the evolutionary study of the CNS, in particular a brain, is of biological significance. In chapter 2, taking the planarian CNS as an example, I, first, examined the evolutionary divergence of the genes that were related to the nervous system, because the planarian is known to possess one of the most primitive brains. To elucidate the evolutionary process of CNS, I then conducted the comparative genomics studies of gene expression profiles in the CNS among different organisms. We sequenced 5,433 5'-ESTs from the cDNA library that was derived from the head portions of planarians (Dugesia japonica), obtaining a total of 3,101 non-redundant EST clones.
To deal with the large amount of EST data, I have developed a computer software package, FinEST, in which an information analysis of EST sequence data including homology search can be done automatically. Conducting the homology search in my software package, I found that 44% of the 3,101 clones had significant similarity of amino acid sequences of gene products whose functions were known. Among these genes, at least 116 genes were found to be homologous to the CNS-related genes. I compared these 116 planarian gene sequences with all ORFs of the complete genome sequences of human,fruit fry and nematode. I then found that 110 genes were evolutionarily shared among all the bilateral animals examined, although only the remaining 6 genes were shared among a limited number of species. This feature of gene conservation can be considered as strong reflection of the selective constraints against CNS-related genes, suggesting that these shared genes are a part of the basic gene set of CNS which might have existed in the common ancestral CNS of bilateral animals. Based on these findings, I proposed a model of the evolutionary process of the CNS.
In chapter 3, with the aim of studying the diversity of the genes expressed in different cell types, we took a comparative approach using the gene expression profiles of single cells of ascidians (Ciona intestinalis). The swimming larval stage of ascidian has two different sensory organs, called \"ocellus\" and \"otolith\". These organs exist in a cerebral vesicle, which is often called as a brain. It has been reported that there are only two pigment cells in a total of about 2,600 cells that form the swimming larva. One pigment cell is found in the ocellus and the other is otolith. Thus, in this study, these pigment cells were called as ocellus cell and otolith cell. To attain our purpose, we examined the expression profiles of the ocellus cell and the otolith cell, and compared the expression profiles between these two different types of cells. First, we sequenced 964 and 774 ESTs from the cDNA libraries of the pigment cells of ocellus and otolith, respectively. As a result, we obtained 485 and 505 non-redundant clones from the ocellus and otolith cells, respectively. The composition of the highly expressed clones illustrated clear difference from that of planarian head ESTs, showing that one of characteristic features of the gene expression profiles in these single cells is less amount of the cytoskeltal genes expressed. Comparing the gene expression profiles between ocellus and otolith cells, we found that 60 clones were commonly
expressed between two pigment cells. The relative frequencies of these 60 clones showed obviously distinct patterns between these two cells. This is the first report about the gene expression profiles of the single cells that compose an organ, showing clear characteristic features of the expression profiles at the single cell level.
In chapter 4, I made an attempt to understand the evolutionary process of a brain from the viewpoint of gene expression profiles. To attain the purpose, I raised a question of whether the degree of the differences in the gene expression profiles of a particular organ between different species corresponds proportionally to the degree of the evolutionary divergence between the species. In practice, we sequenced EST clones from the cDNA libraries of brains of chickens (Gallus gallus) and lampreys (Lampetra japonica), the head of planarians (see above), and the whole body of the jellyfish (Aureria aurita), obtaining over 2,000 clones from each library. If difference of the gene expression profiles corresponds to the evolutionary divergence of species, a topology of the tree based on the difference in the gene expression profiles (designated as a gene expression tree) might correspond to a topology of the species tree. To examine this statement, I quantified the differences in the gene expression profiles between different species by the Euclidean distance, and then constructed a gene expression tree. As a result, the topology of the gene expression tree showed clear correspondence to that of the species tree, though the current number of clones sequenced was still relatively small. Thus, I concluded that the gene expression profiles of brains might reflect the evolutionary process of the brain.
Finally, in chapter 5, I described the summary and conclusion of the present study. I also discussed the future perspectives of the present study. In conclusion, this is the first attempt to conduct an evolutionary study by use of the gene expression profiles, successfully showing that the evolutionary process of the CNS can be traceable by use of the gene expression profiles.","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603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":"2001"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"MINETA, Katsuhiko","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603_要旨.pdf","filesize":[{"value":"414.5 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/973/files/甲603_要旨.pdf"},"version_id":"36bd1c82-d2c7-4366-9053-04ee06f317b7"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲603_本文.pdf","filesize":[{"value":"18.2 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"本文","url":"https://ir.soken.ac.jp/record/973/files/甲603_本文.pdf"},"version_id":"6c8f37cf-7a06-4feb-a6ce-ce1bd03f3fbb"}]},"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 the central nervous system revealed by the comparative approach of the gene expression profiles","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Evolutionary features of the central nervous system revealed by the comparative approach of the gene expression profiles"},{"subitem_title":"Evolutionary features of the central nervous system revealed by the comparative approach of the gene expression profiles","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":"973","relation_version_is_last":true,"title":["Evolutionary features of the central nervous system revealed by the comparative approach of the gene expression profiles"],"weko_creator_id":"1","weko_shared_id":1},"updated":"2023-06-20T14:41:04.659751+00:00"}