{"created":"2023-06-20T13:20:53.486650+00:00","id":956,"links":{},"metadata":{"_buckets":{"deposit":"5b2f06cc-a101-46b5-a01d-a0e8e5f040b4"},"_deposit":{"created_by":1,"id":"956","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"956"},"status":"published"},"_oai":{"id":"oai:ir.soken.ac.jp:00000956","sets":["2:430:20"]},"author_link":["9787","9786","9788"],"item_1_creator_2":{"attribute_name":"著者名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"鈴木, 善幸"}],"nameIdentifiers":[{}]}]},"item_1_creator_3":{"attribute_name":"フリガナ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"スズキ, ヨシユキ"}],"nameIdentifiers":[{}]}]},"item_1_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2000-03-24"}]},"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":"The molecular evolutionary analyses have been conducted to clarify the evolutionary mode and history of pathogenic viruses.  The evolutionary mode and history include (1) the phylogenetic relationships, (2) the rates of nucleotide substitutiolls, (3) the divergence times, (4) the patterns of nucleotide substitutions, and (5) the natural selection.<br />In Chapter I, the significances of analyzing the above subjects are summarized. (1) The investigation of the phylogenetic relationships among virus <br />strains is known as the molecular epidemiology. Once the phylogenetic relationships among virus strains are established, it is possible to identify the transmission routes of the virus within human population. The identification of the transmission route is then useful to infer the possible transmission mode of viruses. The investigation of the phylogenetic relationships among virus strains is also useful to clarify the geographical origin of viruses. Moreover, the comparison of the phylogenetic relationships among virus strains obtained from various host species with the phylogenetic relationships among the host species may indicate the possible occurrence of interspecies transmissions.<br />(2) The studies of the rate of nucleotide substitutions for various viruses clarified that the RNA viruses can be divided into two categories, according to their rates of nucleotide substitutions. The first category consists of the rapidly evolving RNA viruses with the rate of nucleotide substitutions of the order of 10-3 to 10-4 per site per year. The second category includes the slowly evolving RNA viruses with the rate of nucleotide substitutions of the order of 10-6 to 10-7. It implies that the evolutionary theories so far proposed can be tested experimentally using rapidly evolving RNA viruses. The evolutionary rate of viruses is also useful to predict the possibility of developing effective vaccines against viruses.<br />(3) Applying the rate of nucleotide substitutions to the phylogenetic tree reconstructed for virus strains, the divergence times among virus strains can be estimated. The comparison of the divergence times among virus strains with the divergence times among their host species indicates the possible interspecies transmission of viruses.<br />(4) In general, the exact knowledge of the pattern of nucleotide substitutions for a particular organism is important to choose appropriate nucleotide substitution models in the molecular evolutionary analyses for that organism. The study for the pattern of nucleotide substitutiors for viruses is also useful for developing new drugs, particularly nucleotide analogues, against virus infections.<br />(5) The factors determining the mode of molecular evolution include the mutation rate, the random genetic drift, and the natural selection. The mutation rates for the rapidly evolving RNA viruses seem to be more than million times faster than the mutation rate for humans, as is the case for the rate of nucleotide substitutions. According to the neutral theory of molecular evolution, the great majority of evolutionary changes at the molecular level are caused not by positive selection but by random drift of selectively neutral or nearly neutral mutants. However, positive selection operating at the amino acid sequence level has been detected on many protein coding genes of viruses.<br />In Chapter II, studies on human T-cell lymphotropic virus types I(HTLV-I) and II(HTLV-II) are briefly reviewed from the viewpoint of molecular evolution, with special reference to the evolutionary rate ard evolutionary relationships among different isolates of these viruses. In particular, it appears that, in contrast to the low level of variability of HTLV-I among different isolates, individual isolates form quasispecies structures,  Elucidating the underlying mechanisms of these two phenomena will be one of the future problems in the study of the molecular <br />evolution  of HTLV-I and HTLV-II.<br />In Chapter III, with the aim of elucidating evolutionary features of GB virus C/hepatitis G virus (GBV-C/HGV), molecular evolutionary analyses were conducted using the entire coding region of this virus. In particular, the rate of nucleotide substitutions for this virus was estimated to be less than 9.0×10-6 per site per year, which was much slower than those for other RNA viruses. The phylogenetic tree reconstructed for GBV-C/HGV, by using GB virus A (GBV-A) as outgroup, indicated that there were three major clusters(the HG, GB, and Asian types) in GBV-C/HGV, and the divergence between the ancestor of GB and Asian type strains and that of HG type strains first took place more than 7,000-10,000 years ago. The slow evolutionary rate for GBV-C/HGV suggested that this virus cannot escape from the immune response of the host by means of producing escape mutants, implying that it may have evolved other systems for persistent infection.<br />In Chapter IV, molecular evolutionary analyses for Ebola and Marburg viruses were conducted with the aim of elucidating evolutionary features of these viruses. ln Particular, the rate of nonsynonymous substitutions for the glycoprotein (GP) gene of Ebola virus was estimated to be, on the average,3.6×10-5 per site per year. <br />Marburg virus was also suggested to be evolving at a similar rate. Those rates were a hundred times slower than those of retroviruses and human influenza A virus, but were of the same order of magnitude as that of hepatitis B virus. When these rates were applied to the degree of sequence divergence, the divergence time between Ebola and Marburg viruses was estimated to be more than several thousand years ago, Moreover, most of the nucleotide substitutions were transitional and synonymous for Marburg virus.  This observation suggests that purifying selection has operated <br />on Marburg virus during evolution.<br />In Chapter V, a method was developed for detecting the selective force at single amino acid sites, given a multiple alignment of protein coding sequences. The phylogenetic tree was reconstructed using the number of synonymous substitutions. Then, the neutrality was tested for each codon site using the numbers of synonymous and nonsynonymous changes throughout the phylogenetic tree. Computer simulation showed that this method estimated accurately the numbers of synonymous and nonsynonymous substitutions per site, as long as the substitution number on each branch was relatively small. The false positive rate for detecting the selective force was generally low. On the other hand, the true positive rate for  detecting the selective force depended upon the parameter values. Within the range of parameter values used in the simulation, the true positive rate increased as the strength of the selective force and the total branch length, namely the total number of synonymous substitutions per site, in the phylogenetic tree increased. In particular, most of the positively selected codon sites, with the relative rate of nonsynonymous substitulion to synonymous substitution being 5.0, were correctly detected when the total branch length in the phylogenetic tree was 2.5 or more. When this method was applied to the human leukocyte antigen (HLA) gene, which included antigen recognition sites (ARSs), positive selection was detected mainly on ARSs. This finding confirmed the effectiveness of the present method wlth actual data. Moreover, two amino acid sites were newly identified as positively selected in non-ARSs. Three-dimensional structure of the HLA molecule indicated that these sites might be involved in antigen recognition. Positively selected amino acid sites were also identified in the envelope protein of human immunodeficiency virus and the influenza virus hemagglutinin protein. This method is helpful for predicting functions of amino acid sites in proteins, especially in the present situation that sequence data is accumulating at an enormous speed.","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":"総研大乙第78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":"1999"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"SUZUKI, Yoshiyuki","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":"乙78_要旨.pdf","filesize":[{"value":"418.2 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/956/files/乙78_要旨.pdf"},"version_id":"73e4f3d9-b3ac-4106-911e-53c39a00c2dd"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"乙78_本文.pdf","filesize":[{"value":"4.4 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"本文","url":"https://ir.soken.ac.jp/record/956/files/乙78_本文.pdf"},"version_id":"c95662f6-5f85-4378-b82c-b7fe7cf3eca7"}]},"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 evolution of pathogenic viruses","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Molecular evolution of pathogenic viruses"},{"subitem_title":"Molecular evolution of pathogenic viruses","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":"956","relation_version_is_last":true,"title":["Molecular evolution of pathogenic viruses"],"weko_creator_id":"1","weko_shared_id":1},"updated":"2023-06-20T14:43:49.718895+00:00"}