2017年09月, 日本学術振興会, 審査委員表彰　　　　　　　　　　　　　　　
渡邉 日出海

2012年06月, 画像電子学会, 優秀論文賞　　　　　　　　　　　　　　　
補完的投票に基づくオプティカルフローのロバスト推定
方 明;髙氏 秀則;金子 俊一;渡邉 日出海

2001年11月, The fourth international workshop on advanced genomics, The 3rd poster award　　　　　　　　　　　　　　　

壊死性網膜炎を伴うアデノウイルス関連ぶどう膜炎　　　　　　　　　　　　　　　
杉田 直, 臼井 嘉彦, 渡邉 日出海, Laura Panto, 飯田 雅, 杉之下 景介, 小柳 香奈子, 西田 明弘, 栗本 康夫, 髙橋 政代, 進藤 達哉, 西岡 弘晶, 高野 雅彦, 毛塚 剛司, 後藤 浩, 北市 伸義
日本眼科学会雑誌, 127, 10, 930, 930, 2023年10月, ［招待有り］
日本語

Adenovirus-associated uveitis with necrotizing retinitis
Nobuyoshi Kitaichi, Sunao Sugita, Yoshihiko Usui, Hidemi Watanabe, Laura Panto, Miyabi Iida, Keisuke Suginoshita, Kanako K Koyanagi, Akihiro Nishida, Yasuo Kurimoto, Masayo Takahashi, Tatsuya Shindo, Hiroaki Nishioka, Masahiko Takano, Takeshi Kezuka, Hiroshi Goto
Ophthalmology, 130, 4, 443, 445, 2022年12月, ［査読有り］, ［招待有り］, ［筆頭著者］, ［国際誌］
英語, 研究論文（学術雑誌）

アデノウイルスにより急性網膜壊死様の眼所見を呈した1例　　　　　　　　　　　　　　　
臼井 嘉彦, 杉田 直, 國見 敬子, 高野 雅彦, 毛塚 剛司, 後藤 浩, 渡邉 日出海, 北市 伸義
日本眼科学会雑誌, 126, 臨増, 215, 215, (公財)日本眼科学会, 2022年03月
日本語

サイトメガロウイルス網膜炎様壊死性網膜炎を伴うアデノウイルス関連ぶどう膜炎の1例　　　　　　　　　　　　　　　
杉田 直, 西田 明弘, 高橋 政代, 栗本 康夫, 臼井 嘉彦, 渡邉 日出海, 北市 伸義
日本眼科学会雑誌, 126, 臨増, 215, 215, (公財)日本眼科学会, 2022年03月
日本語

ICTV Virus Taxonomy Profile: Adenoviridae 2022
Mária Benkő, Koki Aoki, Niklas Arnberg, Andrew J. Davison, Marcela Echavarría, Michael Hess, Morris S. Jones, Győző L. Kaján, Adriana E. Kajon, Suresh K. Mittal, Iva I. Podgorski, Carmen San Ma, Göran Wadell, Hidemi Watanabe, Balázs Harrach, ICTV Report Consortium
Journal of General Virology, 103, 3, 2022年03月, ［査読有り］, ［招待有り］
英語, 研究論文（学術雑誌）

霊長類北限環境に生息するニホンザルの排泄物メタゲノム解析による食性の解明
藤原 遼人, 小柳 香奈子, 渡邉 日出海
霊長類研究 Supplement, 38, 64, 日本霊長類学会, 2022年
日本語, 非ヒト霊長類の多くは低緯度の熱帯および亜熱帯地域の森林に生息し、主に果実や昆虫などを食べて生活する。一方、非ヒト霊長類中でニホンザルのみが、下北半島を北限とする積雪・落葉・気温低下により果実や昆虫を得られなくなる冬季を有する高緯度地域にも生息している。本研究では、そのようなニホンザルの特異的高緯度環境適応を可能にした要因を明らかにするために、2012年より下北半島に生息する野生ニホンザルの糞便を収集してきた。初秋季および冬季に得たニホンザル糞便試料よりDNAを抽出し、PCR等によるターゲット選択をすること無くOxford Nanopore社のMinIONシステムによる塩基配列決定を行った。その結果得られた計111.1メガ塩基対となる131,120 リード配列データを国際塩基配列データベースに対して相同配列検索を行い、各リード配列の由来生物を推定した。さらに、霊長目以外の真核生物に分類されたリード配列の分類群頻度解析を行うことで、秋季と冬季において下北半島生息ニホンザル集団が摂取している主要食物を推定した。その結果、秋季中は、下北半島に自生しているマタタビ、ヤマブドウなどの高カロリー食を大量に食べ、冬季はアジサイやニシキギなどに依存しているということが示唆された。また、タンパク質源として、海産魚も摂っている可能性や、住血胞子虫などの寄生虫に冒されている可能性も示唆された。これらの結果に基づき、ニホンザルの高緯度地域への適応要因について考察する。

Adenoviridae
Mária Benkő, Koki Aoki, Niklas Arnberg, Andrew J. Davison, Marcela Echavarría, Michael Hess, Morris S. Jones, Győző L. Kaján, Adriana E. Kajon, Suresh K. Mittal, Iva I. Podgorski, Carmen San Martín, Göran Wadell, Hidemi Watanabe, Balázs Harrach
The ICTV Report on Virus Classification and Taxon Nomenclature, 2021年11月, ［国際誌］
英語, 研究論文（その他学術会議資料等）, Adenoviridae is a family of viruses with non-enveloped, icosahedral virions containing linear dsDNA genomes of 25–48 kb (Table 1.Adenoviridae). Its members infect a variety of vertebrate hosts ranging from fish to humans and are allocated to six genera. Members of genus Mastadenovirus infect mammals, those of Aviadenovirus infect birds, Ichtadenovirus has a single fish adenovirus, and strains of genus Testadenovirus occur in turtles. Members of Atadenovirus occur in squamate reptiles, birds, ruminants, marsupials and tortoises, and those of Siadenovirus infect birds, frog and tortoise. The severity of infections ranges from subclinical to lethal. Adenoviruses are popular virus vectors, e.g. for vaccination against the coronavirus SARS-CoV-2.

Genomic characterization of human adenovirus type 4 strains isolated worldwide since 1953 identifies two separable phylogroups evolving at different rates from their most recent common ancestor
Gabriel Gonzalez, Camden R. Bair, Daryl M. Lamson, Hidemi Watanabe, Laura Panto, Michael J. Carr, Adriana E. Kajon
Virology, 538, 11, 23, 2019年, ［査読有り］
英語, 研究論文（学術雑誌）, Species Human mastadenovirus E (HAdV-E) comprises several simian types and a single human type: HAdV-E4, a respiratory and ocular pathogen. RFLP analysis for the characterization of intratypic genetic variability has previously distinguished two HAdV-E4 clusters: prototype (p)-like and a-like. Our analysis of whole genome sequences confirmed two distinct lineages, which we refer to as phylogroups (PGs). PGs I and II comprise the p- and a-like genomes, respectively, and differ significantly in their G + C content (57.7% ± 0.013 vs 56.3% ± 0.015). Sequence differences distinguishing the two clades map to several regions of the genome including E3 and ITR. Bayesian analyses showed that the two phylogroups diverged approximately 602 years before the present. A relatively faster evolutionary rate was identified for PG II. Our data provide a rationale for the incorporation of phylogroup identity to HAdV-E4 strain designation to reflect the identified unique genetic characteristics that distinguish PGs I and II.

Human mastadenovirusにおける流行性角結膜炎原因アミノ酸サイトの探索　　　　　　　　　　　　　　　
飯田 雅, 小柳 香奈子, 日隈 陸太郎, 青木 功喜, 渡邉 日出海
感染症学雑誌, 91, 臨増, 379, 379, (一社)日本感染症学会, 2017年03月
日本語

Comparative genomic analysis of retrogene repertoire in two green algae Volvox carteri and Chlamydomonas reinhardtii
Marcin Jakalski, Kazutaka Takeshita, Mathieu Deblieck, Kanako O. Koyanagi, Izabela Makalowska, Hidemi Watanabe, Wojciech Makalowski
BIOLOGY DIRECT, 11, BIOMED CENTRAL LTD, 2016年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Retroposition, one of the processes of copying the genetic material, is an important RNA-mediated mechanism leading to the emergence of new genes. Because the transcription controlling segments are usually not copied to the new location in this mechanism, the duplicated gene copies (retrocopies) become pseudogenized. However, few can still survive, e.g. by recruiting novel regulatory elements from the region of insertion. Subsequently, these duplicated genes can contribute to the formation of lineage-specific traits and phenotypic diversity. Despite the numerous studies of the functional retrocopies (retrogenes) in animals and plants, very little is known about their presence in green algae, including morphologically diverse species. The current availability of the genomes of both uni- and multicellular algae provides a good opportunity to conduct a genome-wide investigation in order to fill the knowledge gap in retroposition phenomenon in this lineage.
Results: Here we present a comparative genomic analysis of uni-and multicellular algae, Chlamydomonas reinhardtii and Volvox carteri, respectively, to explore their retrogene complements. By adopting a computational approach, we identified 141 retrogene candidates in total in both genomes, with their fraction being significantly higher in the multicellular Volvox. Majority of the retrogene candidates showed signatures of functional constraints, thus indicating their functionality. Detailed analyses of the identified retrogene candidates, their parental genes, and homologs of both, revealed that most of the retrogene candidates were derived from ancient retroposition events in the common ancestor of the two algae and that the parental genes were subsequently lost from the respective lineages, making many retrogenes 'orphan'.
Conclusion: We revealed that the genomes of the green algae have maintained many possibly functional retrogenes in spite of experiencing various molecular evolutionary events during a long evolutionary time after the retroposition events. Our first report about the retrogene set in the green algae provides a good foundation for any future investigation of the repertoire of retrogenes and facilitates the assessment of the evolutionary impact of retroposition on diverse morphological traits in this lineage.
Reviewers: This article was reviewed by William Martin and Piotr Zielenkiewicz.

Interregional Coevolution Analysis Revealing Functional and Structural Interrelatedness between Different Genomic Regions in Human Mastadenovirus D
Gabriel Gonzalez, Kanako O. Koyanagi, Koki Aoki, Hidemi Watanabe
JOURNAL OF VIROLOGY, 89, 12, 6209, 6217, AMER SOC MICROBIOLOGY, 2015年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Human mastadenovirus D (HAdV-D) is exceptionally rich in type among the seven human adenovirus species. This feature is attributed to frequent intertypic recombination events that have reshuffled orthologous genomic regions between different HAdV-D types. However, this trend appears to be paradoxical, as it has been demonstrated that the replacement of some of the interacting proteins for a specific function with other orthologues causes malfunction, indicating that intertypic recombination events may be deleterious. In order to understand why the paradoxical trend has been possible in HAdV-D evolution, we conducted an interregional coevolution analysis between different genomic regions of 45 different HAdV-D types and found that ca. 70% of the genome has coevolved, even though these are fragmented into several pieces via short intertypic recombination hot spot regions. Since it is statistically and biologically unlikely that all of the coevolving fragments have synchronously recombined between different genomes, it is probable that these regions have stayed in their original genomes during evolution as a platform for frequent intertypic recombination events in limited regions. It is also unlikely that the same genomic regions have remained almost untouched during frequent recombination events, independently, in all different types, by chance. In addition, the coevolving regions contain the coding regions of physically interacting proteins for important functions. Therefore, the coevolution of these regions should be attributed at least in part to natural selection due to common biological constraints operating on all types, including protein-protein interactions for essential functions. Our results predict additional unknown protein interactions.
IMPORTANCE
Human mastadenovirus D, an exceptionally type-rich human adenovirus species and causative agent of different diseases in a wide variety of tissues, including that of ocular region and digestive tract, as well as an opportunistic infection in immunocompromised patients, is known to have highly diverged through frequent intertypic recombination events; however, it has also been demonstrated that the replacement of a component protein of a multiprotein system with a homologous protein causes malfunction. The present study solved this apparent paradox by looking at which genomic parts have coevolved using a newly developed method. The results revealed that intertypic recombination events have occurred in limited genomic regions and been avoided in the genomic regions encoding proteins that physically interact for a given function. This approach detects purifying selection against recombination events causing the replacement of partial components of multiprotein systems and therefore predicts physical and functional interactions between different proteins and/or genomic elements.

DNA barcoding of Oeneis butterflies newly sampled in Mongolia
Takatoshi Abe, Hidemi Watanabe, Kanako O. Koyanagi, Botaro Inoue
GENOME, 58, 5, 185, 185, CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS, 2015年05月, ［査読有り］
英語

A Novel Complex Recombinant Form of Type 48-Related Human Adenovirus Species D Isolated in Japan (vol 67, pg 282, 2014)
Tsuguto Fujimoto, Shotaro Yamane, Tomoko Ogawa, Nozomu Hanaoka, Atsushi Ogura, Chiemi Hotta, Takeshi Niwa, Yakou Chiba, Gabriel Gonzalez, Koki Aoki, Kanako Ono Koyanagi, Hidemi Watanabe
JAPANESE JOURNAL OF INFECTIOUS DISEASES, 67, 5, 416, 416, NATL INST INFECTIOUS DISEASES, 2014年09月, ［査読有り］
英語

Intertypic modular exchanges of genomic segments by homologous recombination at universally conserved segments in human adenovirus species D
Gabriel Gonzalez, Kanako O. Koyanagi, Koki Aoki, Nobuyoshi Kitaichi, Shigeaki Ohno, Hisatoshi Kaneko, Susumu Ishida, Hidemi Watanabe
GENE, 547, 1, 10, 17, ELSEVIER SCIENCE BV, 2014年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Human adenovirus species D (HAdV-D), which is composed of clinically and epidemiologically important pathogens worldwide, contains more taxonomic "types" than any other species of the genus Mastadenovirus, although the mechanisms accounting for the high level of diversity remain to be disclosed. Recent studies of known and new types of HAdV-D have indicated that intertypic recombination between distant types contributes to the increasing diversity of the species. However, such findings raise the question as to how homologous recombination events occur between diversified types since homologous recombination is suppressed as nucleotide sequences diverge. In order to address this question, we investigated the distribution of the recombination boundaries in comparison with the landscape of intergenomic sequence conservation assessed according to the synonymous substitution rate (d(s)). The results revealed that specific genomic segments are conserved between even the most distantly related genomes; we call these segments "universally conserved segments" (UCSs). These findings suggest that UCSs facilitate homologous recombination, resulting in intergenomic segmental exchanges of UCS-flanking genomic regions as recombination modules. With the aid of such a mechanism, the haploid genomes of HAdV-Ds may have been reshuffled, resulting in chimeric genomes out of diversified repertoires in the HAdV-D population analogous to the MHC region reshuffled via crossing over in vertebrates. In addition, some HAdVs with chimeric genomes may have had the opportunity to avoid host immune responses thereby causing epidemics. (C) 2014 Elsevier B.V. All rights reserved.

A Novel Complex Recombinant Form of Type 48-Related Human Adenovirus Species D Isolated in Japan
Tsuguto Fujimoto, Shotaro Yamane, Tomoko Ogawa, Nozomu Hanaoka, Atsushi Ogura, Chiemi Hotta, Takeshi Niwa, Yakou Chiba, Gabriel Gonzalez, Koki Aoki, Kanako Ono Koyanagi, Hidemi Watanabe
JAPANESE JOURNAL OF INFECTIOUS DISEASES, 67, 4, 282, 287, NATL INST INFECTIOUS DISEASES, 2014年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Recently, new genotypes of human adenoviruses (HAdVs) have been reported and many of them have been found to be recombinant forms of different known types of HAdV species D (HAdV-D). The objective of this study was to document the evolutionary features of a novel isolate (HAdV_Chiba_E086/2012) obtained from the eye swab of a patient with conjunctivitis in Japan. Viral DNA was extracted from the isolate to sequence the whole genome by the Sanger method and aligned with available genome sequences of HAdV-Ds. The phylogenetic trees of the nucleotide sequences of the penton base, hexon, and fiber genes and the E3 region showed that HAdV_Chiba_E086/2012 is closest to HAdV genotype 65 (HAdV-GT65), HAdV-48, HAdV-GT60 and HAdV-22 at 98%, 99%, 95% and 98% identity, respectively, suggesting that this isolate is a novel recombinant form to be designated as P65H48F60. Further phylogenetic and recombination analyses of the genome alignment of the new isolate implied that nested recombination events involving HAdV-GT59, GT65, 48, GT60, 22, and some ancestral lineages or their close relatives have shaped its genome. These results showed that HAdV_Chiba_E086/2012 is the first HAdV-48-related HAdV found in Japan, which has the most complicated evolutionary history among the known HAdVs so far.

院内感染を起こす新型ヒトアデノウイルスのバイオインフォマティクス
青木功喜, 金子久俊, 北市伸義, 渡邉日出海, 石田晋, 大野重昭
日本眼科学会雑誌, 117, 9, 721, 6, 2013年09月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, 流行性角結膜炎を引き起こすヒトアデノウイルス(HAdV)はすべてD種かE種である。バイオインフォマティクスの進歩により、その病態は宿主の免疫応答に関与するearly transcription unit 3(E3)、標的器官に接着するファイバー.ノブ、細胞に侵入するためのペントンベースにあるRGDモチーフ、中和決定基のヘキソンとその可変領域であるループ１と2という構造が関与することがあきらかになってきた。サルからヒトへ種の壁を越えた感染が起こった可能性が指摘され（HAdV-52型）、さらに近年はゲノムの組み換えによりHAdV-53、-54、-56型などの新型が次々に出現している。バイオインフォマティクスを用いた全ゲノム系統解析をアデノウイルス研究に応用し、臨床と遺伝子の相互関連の解明に取り組み、新しい型の命名法、院内感染の病原体の特定、遺伝子構造と進化、流行の予測と治療薬の標的推定への利用が期待される。

バッテリー駆動による2000m 級小型ROV の開発と運用法の構築
山本 潤, 岩森利弘, 星 直樹, 阿部拓三, 坂岡桂一郎, 亀井佳彦, 高木省吾, 沼本 修, 阪 幸宏, 桜井泰憲, 末岡和久, 有村博紀, 渡邉日出海
水産技術, 5, 2, 171, 174, 水産総合研究センター, 2013年02月, ［査読有り］
日本語, 研究論文（学術雑誌）, We developed a battery powered compact 2000m class ROV (Remotely Operated Vehicle) system with a High-Definition video camera. It does not require specialized equipment to operate. It can be operated using only general purpose equipment. This system mainly consists of a shipboard controller, a vehicle and a launcher. A thin, light optical fiber cable (diameter 9mm, length 2,500m), the primary cable, transfers control data and video images between the shipboard controller and the launcher. The secondary cable, a composite cable (diameter 14.2mm, length 50m), transfers control data and video images and supplies power to the vehicle from the six packs of lithium-ion batteries, which are mounted in the launcher. The launcher is suspended by a rope from the support ship, and the depth of the launcher is adjusted by changing the length of the rope using a general purpose rewinder.

Although initially, we had some trouble due to the launcher rope and the primary cable getting tangled, a newly-designed instrument that restricts the movement of the carabiner, and the use of a low expansion rope, facilitated smoother operation and an easier recovery of the ROV.

Identification of contamination in the American type culture collection stock of human adenovirus type 8 by whole-genome sequencing.
Shotaro Yamane, Amanda Wei Ling Lee, Nozomu Hanaoka, Gabriel Gonzalez, Hisatoshi Kaneko, Susumu Ishida, Nobuyoshi Kitaichi, Shigeaki Ohno, Kanako O Koyanagi, Koki Aoki, Tsuguto Fujimoto, Nobuyo Yawata, Hidemi Watanabe
Journal of virology, 87, 2, 1285, 6, 2, 2013年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Comparative Genome Analysis of Three Eukaryotic Parasites with Differing Abilities To Transform Leukocytes Reveals Key Mediators of Theileria-Induced Leukocyte Transformation
Kyoko Hayashida, Yuichiro Hara, Takashi Abe, Chisato Yamasaki, Atsushi Toyoda, Takehide Kosuge, Yutaka Suzuki, Yoshiharu Sato, Shuichi Kawashima, Toshiaki Katayama, Hiroyuki Wakaguri, Noboru Inoue, Keiichi Homma, Masahito Tada-Umezaki, Yukio Yagi, Yasuyuki Fujii, Takuya Habara, Minoru Kanehisa, Hidemi Watanabe, Kimihito Ito, Takashi Gojobori, Hideaki Sugawara, Tadashi Imanishi, William Weir, Malcolm Gardner, Arnab Pain, Brian Shiels, Masahira Hattori, Vishvanath Nene, Chihiro Sugimoto
MBIO, 3, 5, e00204, 12, AMER SOC MICROBIOLOGY, 2012年09月, ［査読有り］
英語, 研究論文（学術雑誌）, We sequenced the genome of Theileria orientalis, a tick-borne apicomplexan protozoan parasite of cattle. The focus of this study was a comparative genome analysis of T. orientalis relative to other highly pathogenic Theileria species, T. parva and T. annulata. T. parva and T. annulata induce transformation of infected cells of lymphocyte or macrophage/monocyte lineages; in contrast, T. orientalis does not induce uncontrolled proliferation of infected leukocytes and multiplies predominantly within infected erythrocytes. While synteny across homologous chromosomes of the three Theileria species was found to be well conserved overall, subtelomeric structures were found to differ substantially, as T. orientalis lacks the large tandemly arrayed subtelomere-encoded variable secreted protein-encoding gene family. Moreover, expansion of particular gene families by gene duplication was found in the genomes of the two transforming Theileria species, most notably, the TashAT/TpHN and Tar/Tpr gene families. Gene families that are present only in T. parva and T. annulata and not in T. orientalis, Babesia bovis, or Plasmodium were also identified. Identification of differences between the genome sequences of Theileria species with different abilities to transform and immortalize bovine leukocytes will provide insight into proteins and mechanisms that have evolved to induce and regulate this process. The T. orientalis genome database is available at http://totdb.czc.hokudai.ac.jp/.
IMPORTANCE Cancer-like growth of leukocytes infected with malignant Theileria parasites is a unique cellular event, as it involves the transformation and immortalization of one eukaryotic cell by another. In this study, we sequenced the whole genome of a nontransforming Theileria species, Theileria orientalis, and compared it to the published sequences representative of two malignant, transforming species, T. parva and T. annulata. The genome-wide comparison of these parasite species highlights significant genetic diversity that may be associated with evolution of the mechanism(s) deployed by an intracellular eukaryotic parasite to transform its host cell.

顕微鏡画像を用いたSVDDによる深海底生物の分類体系の推定法
長谷川尭史, 小川貴弘, 渡邉日出海, 長谷山美紀
電子情報通信学会技術研究報告, 111, 442(IE2011 105-132), 73, 78, 2012年02月
日本語

In silico and in vivo identification of the intermediate filament vimentin that is downregulated downstream of Brachyury during Xenopus embryogenesis
Atsuko Yamada, Kanako O. Koyanagi, Hidemi Watanabe
GENE, 491, 2, 232, 236, ELSEVIER SCIENCE BV, 2012年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Brachyury, a member of the T-box transcription family, has been suggested to be essential for morphogenetic movements in various processes of animal development. However, little is known about its critical transcriptional targets. In order to identify targets of Brachyury and understand the molecular mechanisms underlying morphogenetic movements, we first searched the genome sequence of Xenopus tropicalis, the only amphibian genomic sequence available, for Brachyury-binding sequences known as T-half sites, and then screened for the ones conserved between vertebrate genomes. We found three genes that have evolutionarily conserved T-half sites in the promoter regions and examined these genes experimentally to determine whether their expressions were regulated by Brachyury, using the animal cap system of Xenopus laevis embryos. Eventually, we obtained evidence that vimentin, encoding an intermediate filament protein, was a potential target of Brachyury. This is the first report to demonstrate that Brachyury might affect the cytoskeletal structure through regulating the expression of an intermediate filament protein, vimentin. (C) 2011 Elsevier B.V. All rights reserved.

Recombination analysis of intermediate human adenovirus type 53 in Japan by complete genome sequence
Hisatoshi Kaneko, Koki Aoki, Susumu Ishida, Shigeaki Ohno, Nobuyoshi Kitaichi, Hiroaki Ishiko, Tsuguto Fujimoto, Yoshifumi Ikeda, Masako Nakamura, Gabriel Gonzalez, Kanako O. Koyanagi, Hidemi Watanabe, Tatsuo Suzutani
JOURNAL OF GENERAL VIROLOGY, 92, 6, 1251, 1259, SOC GENERAL MICROBIOLOGY, 2011年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Human adenovirus type 53 (HAdV-53) has commonly been detected in samples from epidemic keratoconjunctivitis (EKC) patients in Japan since 1996. HAdV-53 is an intermediate virus, containing hexon-chimeric, penton base and fiber structures similar to HAdV-22 and -37, HAdV-37 and HAdV-8, respectively. HAdV-53-like intermediate strains were first isolated from EKC samples in Japan in the 1980s. Here, the complete genome sequences of three such HAdV-53-like intermediate strains (870006C, 880249C and 890357C) and four HAdV-53 strains were determined, and their relationships were analysed. The seven HAdV strains were classified into three groups, 870006C/880249C, 890357C and the four HAdV-53 strains, on the basis of phylogenetic analyses of the partial and complete genome sequences. HAdV strains within the same group showed the highest nucleotide identities (99.87-100.00%). Like HAdV-53, the hexon loop 1 and 2 regions of 870006C, 8802490 and 890357C showed the highest identity with HAdV-22. However, these strains did not show a hexon-chimeric structure similar to HAdV-22 and -37, or a penton base similar to HAdV-37. The fiber genes of 8700060 and 880249C were identical to that of HAdV-37, but not HAdV-8. Thus, the three intermediate HAdVs isolated in the 1980s were similar to each other but not to HAdV-53. The recombination breakpoints were inferred by the Recombination Detection Program (RDP) using whole-genome sequences of these seven HAdV and of 12 HAdV-D strains from GenBank. HAdV-53 may have evolved from intermediate HAdVs circulating in the 1980s, and from HAdV-8, -22 and -37, by recombination of sections cut at the putative breakpoints.

Complete Genome Analysis of a Novel Intertypic Recombinant Human Adenovirus Causing Epidemic Keratoconjunctivitis in Japan
Hisatoshi Kaneko, Koki Aoki, Shigeaki Ohno, Hiroaki Ishiko, Tsuguto Fujimoto, Masayuki Kikuchi, Seiya Harada, Gabriel Gonzalez, Kanako O. Koyanagi, Hidemi Watanabe, Tatsuo Suzutani
JOURNAL OF CLINICAL MICROBIOLOGY, 49, 2, 484, 490, AMER SOC MICROBIOLOGY, 2011年02月, ［査読有り］
英語, 研究論文（学術雑誌）, For 4 months from September 2008, 102 conjunctival swab specimens were collected for surveillance purposes from patients across Japan suspected of having epidemic keratoconjunctivitis (EKC). Human adenovirus (HAdV) DNA was detected in 61 samples by PCR, though the HAdV type for 6 of the PCR-positive samples could not be determined by phylogenetic analysis using a partial hexon gene sequence. Moreover, for 2 months from January 2009, HAdV strains with identical sequences were isolated from five conjunctival swab samples obtained from EKC patients in five different regions of Japan. For the analyses of the 11 samples mentioned above, we determined the nucleotide sequences of the entire penton base, hexon, and fiber genes and early 3 (E3) region, which are variable regions among HAdV types, and compared them to those of other HAdV species D strains. The nucleotide sequences of loops 1 and 2 in the hexons of all 11 samples showed high degrees of identity with those of the HAdV type 15 (HAdV-15) and HAdV-29 prototype strains. However, the fiber gene and E3 region sequences showed high degrees of identity with those of HAdV-9, and the penton base gene sequence showed a high degree of identity with the penton base gene sequences of HAdV-9 and -26. Moreover, the complete genome sequence of the 2307-S strain, which was isolated by viral culture from 1 of the 11 samples, was determined. The 2307-S strain was a recombinant HAdV between HAdV-9, -15, -26, -29, and/or another HAdV type; however, the recombination sites in the genome were not obvious. We propose that this virus is a novel intertypic recombinant, HAdV-15/29/H9, and may be an etiological agent of EKC.

生命系異分野共同研究プロジェクト(北の国から明日のICTに架ける橋,<特別小特集>知の創出を支える次世代IT基盤技術-北海道大学グローバルCOEプログラムと北海道内情報通信系研究グループの活動-)
渡邉 日出海, 金子 俊一, 長谷山 美紀
電子情報通信学会誌, 92, 10, 822, 827, 一般社団法人電子情報通信学会, 2009年10月
日本語

CGAS: comparative genomic analysis server
Masumi Itoh, Hidemi Watanabe
BIOINFORMATICS, 25, 7, 958, 959, OXFORD UNIV PRESS, 2009年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Comparative approach is one of the most essential methods for extracting functional and evolutionary information from genomic sequences. So far, a number of sequence comparison tools have been developed, and most are either for on-site use, requiring program installation but providing a wide variety of analyses, or for the online search of users sequences against given databases on a server. We newly devised an Asynchronous JavaScript and XML (Ajax)-based system for comparative genomic analyses, CGAS, with highly interactive interface within a browser, requiring no software installation. The current version, CGAS version 1, provides functionality for viewing similarity relationships between users sequences, including a multiple dot plot between sequences with their annotation information. The scrollbar-less draggable interface of CGAS is implemented with Google Maps API version 2. The annotation information associated with the genomic sequences compared is synchronously displayed with the comparison view. The multiple-comparison viewer is one of the unique functionalities of this system to allow the users to compare the differences between different pairs of sequences. In this viewer, the system tells orthologous correspondences between the sequences compared interactively. This web-based tool is platform-independent and will provide biologists having no computational skills with opportunities to analyze their own data without software installation and customization of the computer system.

Robust optical flow estimation for underwater image
Ming Fang, Hidenori Takauj, Shun'ichi Kaneko, Hidemi Watanabe
ISOT: 2009 INTERNATIONAL SYMPOSIUM ON OPTOMECHATRONIC TECHNOLOGIES, 185, 190, IEEE, 2009年, ［査読有り］
英語, 研究論文（国際会議プロシーディングス）, This paper describes a novel and robust method of estimating optical flow for underwater image sequences. This method can give out reliable optical flows output, even if the quality of image is very poor. In order to estimate optical flow of current template, first, we divide the template into some sub-templates, and then compute the similarity profiles of each sub. template. These similarity profiles can be used to extract two voting roles: positive voting role and negative voting role. The positive voting role can be used to increase correct optical flows, and the negative voting role can be used to reduce incorrect optical flows. We use two voting qualification variables(T(P), T(Q)) to control the positive and negative voting processing, and use a SNR value to evaluate the each voting result. The estimated optical flow is reliability when the SNR value converge to infinity only by using small T(P) and T(Q).

The effect of gene flow on the coalescent time in the human-chimpanzee ancestral population
H Innan, H Watanabe
MOLECULAR BIOLOGY AND EVOLUTION, 23, 5, 1040, 1047, OXFORD UNIV PRESS, 2006年05月, ［査読有り］
英語, 研究論文（学術雑誌）, The coalescent process in the human-chimpanzee ancestral population is investigated using a model, which incorporates a certain time period of gene flow during the speciation process. a is a parameter to represent the degree and time of gene flow, and the model is identical to the null model with an instantaneous species split when a = infinity. A maximum likelihood (ML) method is developed to estimate a, and its power and reliability is investigated by coalescent simulations. The ML method is applied to nucleotide divergence data between human and chimpanzee. It is found that the null model with an instantaneous species split explains the data best, and no strong evidence for gene flow is detected. The result is discussed in the view of the mode of speciation. Another ML method is developed to estimate the male-female ratio (alpha) of mutation rate, in which the coalescent process in the ancestral population is taken into account.

Ancestral population sizes and species divergence times in the primate lineage on the basis of intron and BAC end sequences
Y Satta, M Hickerson, H Watanabe, C O'hUigin, J Klein
JOURNAL OF MOLECULAR EVOLUTION, 59, 4, 478, 487, SPRINGER, 2004年10月, ［査読有り］
英語, 研究論文（学術雑誌）, The effective sizes of ancestral populations and species divergence times of six primate species (humans, chimpanzees, gorillas, orangutans, and representatives of Old World monkeys and New World monkeys) are estimated by applying the two-species maximum likelihood (ML) method to intron sequences of 20 different loci. Examination of rate heterogeneity of nucleotide substitutions and intragenic recombination identifies five outrageous loci (ODC1, GHR, HBE, INS, and HBG). The estimated ancestral polymorphism ranges from 0.21 to 0.96% at major divergences in primate evolution. One exceptionally low polymorphism occurs when African and Asian apes diverged. However, taking into consideration the possible short generation times in primate ancestors, it is concluded that the ancestral population size in the primate lineage was no smaller than that of extant humans. Furthermore, under the assumption of 6 million years (myr) divergence between humans and chimpanzees, the divergence time of humans from gorillas, orangutans, Old World monkeys, and New World monkeys is estimated as 7.2, 18, 34, and 65 myr ago, respectively, which are generally older than traditional estimates. Beside the intron sequences, three other data sets of orthologous sequences are used between the human and the these data sets including 58,156 random BAC end sequences (BES) shows that the nucleotide substitution rate is as low as 0.6-0.8 x 10(-9) per site per year and the extent of ancestral polymorphism is 0.33-0.51%. With such a low substitution rate and short generation time, the relatively high extent of polymorphism suggests a fairly large effective population size in the ancestral lineage common to humans and chimpanzees.

Finishing the euchromatic sequence of the human genome
Eric S. Lander, Jane Rogers, Robert H. Waterston, Trevor Hawkins, Richar, A. Gibbs, George M. Weinstock, Yoshiyuki Sakaki, Asao Fujiyama, Masahira Hattori, Tetsushi Yada, Atsushi Toyoda, Takehiko Itoh, Chiharu Kawagoe, Hidemi Watanabe, Yasushi Totoki, Todd Taylor, Jean Weissenbach, Douglas R. Smith, André Rosenthal, Huanming Yang, Guyang Huang, et al
NATURE, 431, 7011, 931, 945, NATURE PUBLISHING GROUP, 2004年10月, ［査読有り］, ［招待有り］
英語, 研究論文（学術雑誌）, The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers similar to99% of the euchromatic genome and is accurate to an error rate of similar to1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human genome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead.

DNA sequence and comparative analysis of chimpanzee chromosome 22
H Watanabe, A Fujiyama, M Hattori, TD Taylor, A Toyoda, Y Kuroki, H Noguchi, A BenKahla, H Lehrach, R Sudbrak, M Kube, S Taenzer, P Galgoczy, M Platzer, M Scharfe, G Nordsiek, HB Blocker, Hellmann, I, P Khaitovich, S Paabo, R Reinhardt, HJ Zheng, XL Zhang, GF Zhu, BF Wang, G Fu, SX Ren, GP Zhao, Z Chen, YS Lee, JE Cheong, SH Choi, KM Wu, TT Liu, KJ Hsiao, SF Tsai, CG Kim, S Oota, T Kitano, Y Kohara, N Saitou, HS Park, SY Wang, ML Yaspo, Y Sakaki
NATURE, 429, 6990, 382, 388, NATURE PUBLISHING GROUP, 2004年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Human-chimpanzee comparative genome research is essential for narrowing down genetic changes involved in the acquisition of unique human features, such as highly developed cognitive functions, bipedalism or the use of complex language. Here, we report the high-quality DNA sequence of 33.3 megabases of chimpanzee chromosome 22. By comparing the whole sequence with the human counterpart, chromosome 21, we found that 1.44% of the chromosome consists of single-base substitutions in addition to nearly 68,000 insertions or deletions. These differences are sufficient to generate changes in most of the proteins. Indeed, 83% of the 231 coding sequences, including functionally important genes, show differences at the amino acid sequence level. Furthermore, we demonstrate different expansion of particular subfamilies of retrotransposons between the lineages, suggesting different impacts of retrotranspositions on human and chimpanzee evolution. The genomic changes after speciation and their biological consequences seem more complex than originally hypothesized.

A comprehensive analysis of allelic methylation status of CpG islands on human chromosome 21q
Y Yamada, H Watanabe, F Miura, H Soejima, M Uchiyama, T Iwasaka, T Mukai, Y Sakaki, T Ito
GENOME RESEARCH, 14, 2, 247, 266, COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2004年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Approximately half of all human genes have CpG islands (CGIs) around their promoter regions. Although CGIs usually escape methylation, those on Chromosome X in females and those in the vicinity of imprinted genes are exceptions: They have both methylated and unmethylated alleles to display a "composite" pattern in methylation analysis. In addition, aberrant methylation of CGIs is known to often occur in cancer cells. Here we developed a simple Hpall-McrBC PCR method for discrimination of full, null, incomplete, and composite methylation patterns, and applied it to all computationally identified CGIs on human Chromosome 21q. This comprehensive analysis revealed that, although most CGIs (103 out of 149) escape methylation, a sizable fraction (31 out of 149) are fully methylated even in normal peripheral blood cells. Furthermore, we identified seven CGIs showing the composite methylation, and demonstrated that three of them are indeed methylated monoallelically. Further analyses using informative pedigrees revealed that two of the three are subject to maternal allele-specific methylation. Intriguingly, the other CGI is methylated in an allele-specific but parental-origin-independent manner. Thus, the cell seems to have a broader repertoire of methylating CGIs than previously thought, and our approach may contribute to uncover novel modes of allelic methylation.

Human versus chimpanzee chromosome-wide sequence comparison and its evolutionary implication
Y Sakaki, H Watanabe, T Taylor, M Hattori, A Fujiyama, A Toyoda, Y Kuroki, T Itoh, N Saitou, S Oota, CG Kim, T Kitano, H Lehrach, ML Yaspo, R Sudbrak, A Kahla, R Reinhardt, M Kube, M Platzer, S Taenzer, P Galgoczy, A Kel, H Bloecker, M Scharfe, G Nordsiek, Hellmann, I, P Khaitovich, S Paabo, Z Chen, SY Wang, SX Ren, XL Zhang, HJ Zheng, GF Zhu, BF Wang, GP Zhao, SF Tsai, K Wu, TT Liu, KJ Hsiao, HS Park, YS Lee, JE Cheong, SH Choi
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 68, 455, 460, COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2003年, ［査読有り］
英語, 研究論文（学術雑誌）

比較ゲノムから見たタンパク質立体構造
渡邊 日出海
生物物理, 43, S4, 一般社団法人 日本生物物理学会, 2003年
日本語

Genome sequence of the endocellular obligate symbiont of tsetse flies, Wigglesworthia glossinidia
L Akman, A Yamashita, H Watanabe, K Oshima, T Shiba, M Hattori, S Aksoy
NATURE GENETICS, 32, 3, 402, 407, NATURE AMERICA INC, 2002年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Many insects that rely on a single food source throughout their developmental cycle harbor beneficial microbes that provide nutrients absent from their restricted diet. Tsetse flies, the vectors of African trypanosomes, feed exclusively on blood and rely on one such intracellular microbe for nutritional provisioning and fecundity. As a result of co-evolution with hosts over millions of years, these mutualists have lost the ability to survive outside the sheltered environment of their host insect cells. We present the complete annotated genome of Wigglesworthia glossinidia brevipalpis, which is composed of one chromosome of 697,724 base pairs (bp) and one small plasmid, called pWig1, of 5,200 bp. Genes involved in the biosynthesis of vitamin metabolites, apparently essential for host nutrition and fecundity, have been retained. Unexpectedly, this obligate's genome bears hallmarks of both parasitic and free-living microbes, and the gene encoding the important regulatory protein DnaA is absent.

Construction and analysis of a human-chimpanzee comparative clone map
A Fujiyama, H Watanabe, A Toyoda, TD Taylor, T Itoh, SF Tsai, HS Park, ML Yaspo, H Lehrach, Z Chen, G Fu, N Saitou, K Osoegawa, PJ de Jong, Y Suto, M Hattori, Y Sakaki
SCIENCE, 295, 5552, 131, 134, AMER ASSOC ADVANCEMENT SCIENCE, 2002年01月, ［査読有り］
英語, 研究論文（学術雑誌）, The recently released human genome sequences provide us with reference data to conduct comparative genomic research on primates, which will be important to understand what genetic information makes us human. Here we present a first-generation human-chimpanzee comparative genome map and its initial analysis. The map was constructed through paired alignment of 77,461 chimpanzee bacterial artificial chromosome end sequences with publicly available human genome sequences. We detected candidate positions, including two clusters on human chromosome 21 that suggest large, nonrandom regions of difference between the two genomes.

Prediction of Target Substrates of Transporters in Escherichia coli
Matsusaki Shin-ichi, Watanabe Hidemi, Oshima Taku, Kanaya Shigehiko, Mori Hirotada
Genome Informatics, 13, 394, 395, Japanese Society for Bioinformatics, 2002年
英語

Accumulation of species-specific amino acid replacements that cause loss of particular protein functions in Buchnera, an endocellular bacterial symbiont
S Shigenobu, H Watanabe, Y Sakaki, H Ishikawa
JOURNAL OF MOLECULAR EVOLUTION, 53, 4-5, 377, 386, SPRINGER-VERLAG, 2001年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Endosymbiotic bacteria live in animal cells and are transmitted vertically at the time of the host's reproduction. In view of their small and asexual populations with infrequent chances of recombination, these endocellular bacteria are expected to accumulate mildly deleterious mutations. Previous studies showed that the DNA sequences of these bacteria evolved faster than those of free-living bacteria. In this study, we compared all the ORFs of Buchnera, an endocellular bacterial symbiont of aphids, with those of 34 other prokaryotic organisms and estimated the effect of the accelerated evolution of Buchnera on the functions of its proteins. It was revealed that Buchnera proteins contain many mutations at the sites where sequences are conserved in their orthologues in many other organisms. In addition, amino acid replacements at the conserved sites are mostly changes to physicochemically different amino acids. These results suggest that functions and conformations of Buchnera proteins have been seriously impaired or strongly modified. Indeed, extensive loss of functional motifs was observed in some Buchnera proteins. In many Buchnera proteins mutations were not detected evenly throughout each molecule but tended to accumulate in some functional units, possibly leading to loss of specific functions. As Buchnera has an unusual and limited gene repertory, it is conceivable that the manner of interactions among its proteins has been changed, and thus, functional constraints over their amino acid residues have also been changed during evolution. This may account for the loss of some functional units only in the Buchnera proteins. We obtained evidence that amino acid replacements in Buchnera were not always deleterious, but neutral or, in some cases, even positively selected.

A genomic timescale for the origin of eukaryotes
S. Blair Hedges, Hsiong Chen, Sudhir Kumar, Daniel Y-C Wang, Amanda S. Thompson, Hidemi Watanabe
BMC EVOLUTIONARY BIOLOGY, 1, BIOMED CENTRAL LTD, 2001年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Genomic sequence analyses have shown that horizontal gene transfer occurred during the origin of eukaryotes as a consequence of symbiosis. However, details of the timing and number of symbiotic events are unclear. A timescale for the early evolution of eukaryotes would help to better understand the relationship between these biological events and changes in Earth's environment, such as the rise in oxygen. We used refined methods of sequence alignment, site selection, and time estimation to address these questions with protein sequences from complete genomes of prokaryotes and eukaryotes.
Results: Eukaryotes were found to evolve faster than prokaryotes, with those eukaryotes derived from eubacteria evolving faster than those derived from archaebacteria. We found an early time of divergence (similar to 4 billion years ago, Ga) for archaebacteria and the archaebacterial genes in eukaryotes. Our analyses support at least two horizontal gene transfer events in the origin of eukaryotes, at 2.7 Ga and 1.8 Ga. Time estimates for the origin of cyanobacteria (2.6 Ga) and the divergence of an early-branching eukaryote that lacks mitochondria (Giardia) (2.2 Ga) fall between those two events.
Conclusions: We find support for two symbiotic events in the origin of eukaryotes: one premitochondrial and a later mitochondrial event. The appearance of cyanobacteria immediately prior to the earliest undisputed evidence for the presence of oxygen (2.4-2.2 Ga) suggests that the innovation of oxygenic photosynthesis had a relatively rapid impact on the environment as it set the stage for further evolution of the eukaryotic cell.

Codon and Base Biases after the Initiation Codon of the Open Reading Frames in the Escherichia coli Genome and Their Influence on the Translation Efficiency
T. Sato, M. Terabe, H. Watanabe, T. Gojobori, C. Hori-Takemoto, K.-i. Miura
Journal of Biochemistry, 129, 6, 851, 860, Oxford University Press (OUP), 2001年06月01日
研究論文（学術雑誌）

Initial sequencing and analysis of the human genome
ES Lander, Int Human Genome Sequencing Consortium, LM Linton, B Birren, C Nusbaum, MC Zody, J Baldwin, K Devon, K Dewar, M Doyle, W FitzHugh, R Funke, D Gage, K Harris, A Heaford, J Howland, L Kann, J Lehoczky, R LeVine, P McEwan, K McKernan, J Meldrim, JP Mesirov, C Miranda, W Morris, J Naylor, C Raymond, M Rosetti, R Santos, A Sheridan, C Sougnez, N Stange-Thomann, N Stojanovic, A Subramanian, D Wyman, J Rogers, J Sulston, R Ainscough, S Beck, D Bentley, J Burton, C Clee, N Carter, A Coulson, R Deadman, P Deloukas, A Dunham, Dunham, I, R Durbin, L French, D Grafham, S Gregory, T Hubbard, S Humphray, A Hunt, M Jones, C Lloyd, A McMurray, L Matthews, S Mercer, S Milne, JC Mullikin, A Mungall, R Plumb, M Ross, R Shownkeen, S Sims, RH Waterston, RK Wilson, LW Hillier, JD McPherson, MA Marra, ER Mardis, LA Fulton, AT Chinwalla, KH Pepin, WR Gish, SL Chissoe, MC Wendl, KD Delehaunty, TL Miner, A Delehaunty, JB Kramer, LL Cook, RS Fulton, DL Johnson, PJ Minx, SW Clifton, T Hawkins, E Branscomb, P Predki, P Richardson, S Wenning, T Slezak, N Doggett, JF Cheng, A Olsen, S Lucas, C Elkin, E Uberbacher, M Frazier, RA Gibbs, DM Muzny, SE Scherer, JB Bouck, EJ Sodergren, KC Worley, CM Rives, JH Gorrell, ML Metzker, SL Naylor, RS Kucherlapati, DL Nelson, GM Weinstock, Y Sakaki, A Fujiyama, M Hattori, T Yada, A Toyoda, T Itoh, C Kawagoe, H Watanabe, Y Totoki, T Taylor, J Weissenbach, R Heilig, W Saurin, F Artiguenave, P Brottier, T Bruls, E Pelletier, C Robert, P Wincker, A Rosenthal, M Platzer, G Nyakatura, S Taudien, A Rump, HM Yang, J Yu, J Wang, GY Huang, J Gu, L Hood, L Rowen, A Madan, SZ Qin, RW Davis, NA Federspiel, AP Abola, MJ Proctor, RM Myers, J Schmutz, M Dickson, J Grimwood, DR Cox, MV Olson, R Kaul, C Raymond, N Shimizu, K Kawasaki, S Minoshima, GA Evans, M Athanasiou, R Schultz, BA Roe, F Chen, HQ Pan, J Ramser, H Lehrach, R Reinhardt, WR McCombie, M de la Bastide, N Dedhia, H Blocker, K Hornischer, G Nordsiek, R Agarwala, L Aravind, JA Bailey, A Bateman, S Batzoglou, E Birney, P Bork, DG Brown, CB Burge, L Cerutti, HC Chen, D Church, M Clamp, RR Copley, T Doerks, Eddy, SR, EE Eichler, TS Furey, J Galagan, JGR Gilbert, C Harmon, Y Hayashizaki, D Haussler, H Hermjakob, K Hokamp, WH Jang, LS Johnson, TA Jones, S Kasif, A Kaspryzk, S Kennedy, WJ Kent, P Kitts, EV Koonin, Korf, I, D Kulp, D Lancet, TM Lowe, A McLysaght, T Mikkelsen, JV Moran, N Mulder, VJ Pollara, CP Ponting, G Schuler, Schultz, JR, G Slater, AFA Smit, E Stupka, J Szustakowki, D Thierry-Mieg, J Thierry-Mieg, L Wagner, J Wallis, R Wheeler, A Williams, YI Wolf, KH Wolfe, SP Yang, RF Yeh, F Collins, MS Guyer, J Peterson, A Felsenfeld, KA Wetterstrand, A Patrinos, MJ Morgan
NATURE, 409, 6822, 860, 921, NATURE PUBLISHING GROUP, 2001年02月, ［査読有り］
英語, The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

Lineage-specific loss and divergence of functionally linked genes in eukaryotes
L. Aravind, Hidemi Watanabe, David J. Lipman, Eugene V. Koonin
Proceedings of the National Academy of Sciences, 97, 21, 11319, 11324, Proceedings of the National Academy of Sciences, 2000年10月03日
研究論文（学術雑誌）, By comparing 4,344 protein sequences from fission yeast Schizosaccharomyces pombe with all available eukaryotic sequences, we identified those genes that are conserved in S. pombe and nonfungal eukaryotes but are missing or highly diverged in the baker's yeast Saccharomyces cerevisiae . Since the radiation from the common ancestor with S. pombe , S. cerevisiae appears to have lost about 300 genes, and about 300 more genes have diverged by far beyond expectation. The most notable feature of the set of genes lost in S. cerevisiae is the coelimination of functionally connected groups of proteins, such as the signalosome and the spliceosome components. We predict similar coelimination of the components of the posttranscriptional gene-silencing system that includes the recently identified RNA-dependent RNA polymerase. Because one of the functions of posttranscriptional silencing appears to be “taming” of retrotransposons, the loss of this system in yeast could have triggered massive retrotransposition, resulting in elimination of introns and subsequent loss of spliceosome components that become dispensable. As the genome database grows, systematic analysis of coordinated gene loss may become a general approach for predicting new components of functional systems or even defining previously unknown functional complexes.

Erratum　　　　　　　　　　　　　　　
Hattori M, Fujiyama A, Taylor T. D, Watanabe H, Yada T, Park H. S, Toyoda A, Ishll K, Totoki Y, Choi D. K, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudlen S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis S. E, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Relchelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo M. L
Nature, 407, 6800, 110, 2000年09月07日
英語

Genome sequence of the endocellular bacterial symbiont of aphids Buchnera sp APS
S Shigenobu, H Watanabe, M Hattori, Y Sakaki, H Ishikawa
NATURE, 407, 6800, 81, 86, MACMILLAN PUBLISHERS LTD, 2000年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Almost all aphid species (Homoptera, Insecta) have 60-80 huge cells called bacteriocytes, within which are round-shaped bacteria that are designated Buchnera(1). These bacteria are maternally transmitted to eggs and embryos through host generations, and the mutualism between the host and the bacteria is so obligate that neither can reproduce independently(2). Buchnera is a close relative of Escherichia coli(3), but it contains more than 100 genomic copies per cell(4), and its genome size is only a seventh of that of E. coli(5). Here we report the complete genome sequence of Buchnera sp. strain APS, which is composed of one 640,681-base-pair chromosome and two small plasmids. There are genes for the biosyntheses of amino acids essential for the hosts in the genome, but those for non-essential amino acids are missing, indicating complementarity and syntrophy between the host and the symbiont. In addition, Buchnera lacks genes for the biosynthesis of cell-surface components, including lipopolysaccharides and phospholipids, regulator genes and genes involved in defence of the cell. These results indicate that Buchnera is completely symbiotic and viable only in its limited niche, the bacteriocyte.

Sequence-based structural features between Kvlqt1 and Tapa1 on mouse chromosome 7F4/F5 corresponding to the Beckwith-Wiedemann syndrome region on human 11p15.5: Long-stretches of unusually well conserved intronic sequences of Kvlqt1 between mouse and human
H Yatsuki, H Watanabe, M Hattori, K Joh, H Soejima, H Komoda, ZH Xin, Zhu, X, K Higashimoto, M Nishimura, S Kuratomi, H Sasaki, Y Sakaki, T Mukai
DNA RESEARCH, 7, 3, 195, 206, UNIVERSAL ACADEMY PRESS INC, 2000年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Mouse chromosome 7F4/F5 is a syntenic locus of human 11p15.5 in which many imprinted genes are clustered. Transmission of aberrant human 11p15.5 or duplicated 11p causes Beckwith-Wiedemann syndrome (BWS) depending on which parent the chromosome is derived from. To analyze a syntenic mouse locus corresponding to human 11p15.5, mouse BAC contigs were constructed between Nap2 and Tapa1, in which 390 kb was sequenced between Kvlqt1 and Tapa1. An unexpected finding was that of highly conserved intronic sequences of Kvlqt1 between mouse and human, and their homologies came up to at least 160 kb because the length of this gene extended to 350 kb, suggesting the possibility of some functional constraint due to transcriptional and/or post-transcriptional regulation of this region. Many expressed sequence tags (ESTs) were mapped on this locus. Three genes, Lit1 (Kvlqt1-AS), Mtr1 and Tssc4, were identified and characterized. Lit1 is an antisense-transcript of Kvlqt1 and paternally expressed and maternally methylated throughout the developmental stage. The position where Lit1 exists corresponded to a highly conserved region between mouse and human. This transcript extends at least 60 kb from downstream to upstream of exon 10 in Kvlqt1. Tssc4 and Mtr1 carried putative open reading frames but neither was imprinted. Further characterization of this locus based on the sequence comparison between mouse and human will contribute valuable information towards resolving the mechanism of the occurrence of BWS and the associated childhood turner.

The DNA sequence of human chromosome 21
M Hattori, A Fujiyama, TD Taylor, H Watanabe, T Yada, HS Park, A Toyoda, K Ishii, Y Totoki, DK Choi, E Soeda, M Ohki, T Takagi, Y Sakaki, S Taudien, K Blechschmidt, A Polley, U Menzel, J Delabar, K Kumpf, R Lehmann, D Patterson, K Reichwald, A Rump, M Schillhabel, A Schudy, W Zimmermann, A Rosenthal, J Kudoh, K Shibuya, K Kawasaki, S Asakawa, A Shintani, T Sasaki, K Nagamine, S Mitsuyama, SE Antonarakis, S Minoshima, N Shimizu, G Nordsiek, K Hornischer, P Brandt, M Scharfe, O Schon, A Desario, J Reichelt, G Kauer, H Blocker, J Ramser, A Beck, S Klages, S Hennig, L Riesselmann, E Dagand, T Haaf, S Wehrmeyer, K Borzym, K Gardiner, D Nizetic, F Francis, H Lehrach, R Reinhardt, ML Yaspo, Y Groner
NATURE, 405, 6784, 311, 319, MACMILLAN MAGAZINES LTD, 2000年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.

Dynamic evolution of genomes and the concept of genome space
MI Bellgard, T Itoh, H Watanabe, T Imanishi, T Gojobori
MOLECULAR STRATEGIES IN BIOLOGICAL EVOLUTION, 870, 293, 300, NEW YORK ACAD SCIENCES, 1999年, ［査読有り］
英語, 研究論文（学術雑誌）, A new era in the elucidation of genome evolution has been heralded with the availability of numerous genome sequences. With these data, it has been possible to study evolutionary processes at a greater level of detail in order to characterize features such as gene shuffling, genome rearrangements, base bias composition, and horizontal gene transfer. In this paper, we discuss the evolutionary implications of significant rearrangements within genomes as well as characteristic genomic regions that have been conserved across genomes, This is based on our analysis of orthologous and paralogous genes, We argue that genome plasticity has most likely contributed substantially to the dynamic evolution of genomes, We also describe the characteristic mosaic features of an archaea genome that is comprised of both bacterial and eukaryal elements. Here we investigate base compositional differences as well as the similarity of this species' genes to either bacteria or eukarya, We conclude that these features can be largely explained by the mechanism of horizontal gene transfer. Finally, we introduce the concept of genome space which is defined as the entire set of genomes of all living organisms. We explain its usefulness to describe as well as to gain deeper insight into the general features of the dynamic genomic evolutionary process.

Bacterial features in the genome of Methanococcus jannaschii in terms of gene composition and biased base composition in ORFs and their surrounding regions
H Watanabe, T Gojobori, K Miura
GENE, 205, 1-2, 7, 18, ELSEVIER SCIENCE BV, 1997年12月, ［査読有り］
英語, 研究論文（学術雑誌）, As a result of genome projects, the complete nucleotide sequence of the entire genome of an archaeon, Methanococcus jannaschii, was recently determined as well as other complete sequences of bacterial and eucaryal genomes. When all the 1680 predicted protein-cloning genes of M. jannaschii were classified on the basis of sequence similarity, it was found that this archaeon had a chimeric set of 1016 bacterial-type, 471 eucaryal-type and 193 species- or archaebacteria-specific genes. However, most of the genes predicted to be involved in translation and transcription pathways including RNA genes were of the eucaryal-type with only a few exceptions such as 16S ribosomal RNA and some translation factor-like genes. This appeared curious since previous studies indicated that methanogens have bacterial features in gene organization and expression. To understand the apparent inconsistency between physiological observations and the result of the classification of genes for transcription and translation, we examined the structural relatedness of the genome of M. jannaschii to those of other species. In practice, we compared base compositional patterns in ORFs and their surrounding regions. This made it possible to reveal the relationships among the translation-and transcription-related structures in genomes. In this study, we conducted a statistical test called 'G-test' to evaluate the base biases around the boundaries of ORFs. We then found that M. jannaschii possesses more bacterial features in base biases than eucaryal ones, e.g. strong G biases at the positions corresponding to the Shine-Dalgarno site. This indicates that the few exceptional bacterial genes for translation, such as 16S ribosomal RNA and translation factor-like genes, play crucial roles in the translation pathway in M. jannaschii. The possibility that the genome structure in the last common ancestor of all present species was bacterial is discussed. (C) 1997 Elsevier Science B.V.

Characteristic distribution of bases and codons around the initiation and termination codons in whole reading frames in bacteria and yeast genomes.
Watanabe H, Gojobori T, Terabe M, Wakiyama M, Miura K
Nucleic Acids Symp Ser, 37, 297, 298, 1997年, ［査読有り］

Evolutionary motif and its biological and structural significance
Y Tateno, K Ikeo, T Imanishi, H Watanabe, T Endo, Y Yamaguchi, Y Suzuki, K Takahashi, K Tsunoyama, M Kawai, Y Kawanishi, K Naitou, T Gojobori
JOURNAL OF MOLECULAR EVOLUTION, 44, Suppl 1, S38, S43, SPRINGER VERLAG, 1997年, ［査読有り］
英語, 研究論文（学術雑誌）, We developed a method for multiple alignment of protein sequences. The main feature of this method is that it takes the evolutionary relationships of the proteins in question into account repeatedly for execution, until the relationships and alignment results are in agreement. We then applied this method to the data of the international DNA sequence databases, which are the most comprehensive and updated DNA databases in the world, in order to estimate the ''evolutionary motif'' by extensive use of a supercomputer. Though a few problems needed to be solved, we could estimate the length of the motifs in the range of 20 to 200 amino acids, with about 60 the most frequent length. We then discussed their biological and structural significance. We believe that we are now in a position to analyze DNA and protein not only in vivo and in vitro but also in silico.

Genome plasticity as a paradigm of eubacteria evolution
H Watanabe, H Mori, T Itoh, T Gojobori
JOURNAL OF MOLECULAR EVOLUTION, 44, Suppl 1, S57, S64, SPRINGER, 1997年, ［査読有り］
英語, 研究論文（学術雑誌）, To test the hypotheses that eubacterial genomes leave evolutionarily stable structures and that the variety of genome size is brought about through genome doubling during evolution, the genome structures of Haemophilus influenzae, Mycoplasma genitalium, Escherichia coli, and Bacillus subtilis were compared using the DNA sequences of the entire genome or substantial portions of genome. In these comparisons, the locations of orthologous genes were examined among different genomes. Using orthologous genes for the comparisons guaranteed that differences revealed in physical location would reflect changes in genome structure after speciation. We found that dynamic rearrangements have so frequently occurred in eubacterial genomes as to break operon structures during evolution, even after the relatively recent divergence between E. coli and H. influenzae. Interestingly, in such eubacterial genomes of high plasticity, we could find several highly conservative regions with the longest conserved region comprising the S10, spc, and alpha operons. This suggests that such exceptional conservative regions have undergone strong structural constraints during evolution.

Evolution of transcriptional regulation system through promiscuous coupling of regulatory proteins with operons; Suggestion from protein sequence similarities in Escherichia coli
J Otsuka, H Watanabe, KT Mori
JOURNAL OF THEORETICAL BIOLOGY, 178, 2, 183, 204, ACADEMIC PRESS LTD, 1996年01月, ［査読有り］
英語, As an advanced molecular study of the problems of the evolution of organisms, the transcriptional regulation system is studied by investigating the amino acid sequence similarities between the proteins in the regulation system of Escherichia coli in which the data of sequenced proteins as well as of regulator-regulon relationships are accumulated. The similarities between the proteins are calculated by the FASTA algorithm and their homology is also evaluated in terms of statistical significance with the use of the RDF2 program. This investigation reveals that the similarity between the regulatory protein and the regulated protein is hardly found, but many similarities are found between regulatory proteins and between regulated proteins. These similarity relations are compared with the regulator-regulon relationships ascertained experimentally. From this comparison, it is found that similar regulatory proteins rarely regulate the transcription of similar protein genes. As most of the highly similar proteins are considered to have diverged from a common ancestral protein, this finding strongly suggests the possibility that descendant regulatory proteins have been promiscuously coupled with descendant operons, independently of their ancestral regulator-regulon relationship, and that some of the couplings have been fixed by selection to form the present system of transcriptional regulation. The compatibility of such promiscuous coupling with regulatory organization is illustrated in the carbohydrate transport systems and the succeeding metabolic pathways, whose organization is comprehensive in sending nutritious substances to the central path of glycolysis under different environmental conditions. The benefit of flexibility in regulator-regulon relationships in evolutionary processes is also discussed in connection with the punctuational divergence of species in macroevolution and the cell differentiation in multicellular organisms. (C) 1996 Academic Press Limited

A COMPREHENSIVE REPRESENTATION OF EXTENSIVE SIMILARITY LINKAGE BETWEEN LARGE NUMBERS OF PROTEINS
H WATANABE, J OTSUKA
COMPUTER APPLICATIONS IN THE BIOSCIENCES, 11, 2, 159, 166, OXFORD UNIV PRESS, 1995年04月, ［査読有り］
英語, 研究論文（学術雑誌）, A method is described for the representation of a bird's-eye view of similarity relationships between large numbers of proteins. With the aid of single-linkage clustering, proteins ave clustered into groups on the basis of various types of similarity such as sequence similarity estimated between all the protein pairs. Proteins in a group are directly or indirectly connected to all proteins in the same group by similarities higher than a given threshold and show no similarity higher than the threshold to any proteins outside the group. Thus, all the proteins directly or indirectly related to a protein can be selected out of a large number of proteins by the clustering. Recursion of this clustering of proteins in each group leads to further classification of the proteins. The similarity relationships in each group are visually represented by a similarity matrix. This representation has the advantage of easy detection of the existence of multidomain proteins and diverged families as well as closely related proteins. Such an exhaustive approach to similarity relationships of proteins will be useful for revealing functional/structural/evolutionary units in proteins.

A comprehensive representation of extensive similarity linkage between large numbers of proteins
Hidemi Watanabe, Jinya Otsuka
Bioinformatics, 11, 2, 159, 166, 1995年04月, ［査読有り］
英語, 研究論文（学術雑誌）, A method is described for the representation of a bird's-eye view of similarity relationships between large numbers of proteins. With the aid of single-linkage clustering, proteins are clustered into groups on the basis of various types of similarity such as sequence similarity estimated between all the protein pairs. Proteins in a group are directly or indirectly connected to all proteins in the same group by similarities higher than a given threshold and show no similarity higher than the threshold to any proteins outside the group. Thus, all the proteins directly or indirectly related to a protein can be selected out of a large number of proteins by the clustering. Recursion of this clustering of proteins in each group leads to further classification of the proteins. The similarity relationships in each group are visually represented by a similarity matrix. This representation has the advantage of easy detection of the existence of multidomain proteins and diverged families as well as closely related proteins. Such an exhaustive approach to similarity relationships of proteins will be useful for revealing functional/structural/evolutionary units in proteins. © 1995 Oxford University Press.

Escherichia coli K12 genomic database.
Kunisawa T, Nakamura M, Watanabe H, Otsuka J, Tsugita A, Yeh LS, George DG, Barker WC
Protein Seq Data Anal, 3, 2, 157, 162, 1990年06月, ［査読有り］

疾患関連一塩基多型の民族間不均一分布に関する分析
和島史明, 小柳香奈子, 渡邉日出海, 日本分子生物学会年会プログラム・要旨集(Web), 45th, 2022年

長鎖DNA全長の配列非依存定温増幅法の開発
杉之下景介, 小柳香奈子, 渡邊日出海, 日本分子生物学会年会プログラム・要旨集(Web), 45th, 2022年

Nanopore selective sequencingによる微量未知病原体DNAの検出
松本彩果, 渡邉日出海, 小柳香奈子, 日本分子生物学会年会プログラム・要旨集(Web), 44th, 2021年

鱗翅目タテハチョウ科Oeneis属における異所的平行進化の証明を目指すゲノム比較解析
加藤喜大, 渡邉日出海, 小柳香奈子, 井上望太郎, 松本彩果, 日本分子生物学会年会プログラム・要旨集(Web), 43rd, 2020年

1分子シーケンス技術とcomputational target enrichmentを組み合わせた宿主細胞に潜伏するウイルスゲノムの全ゲノムシーケンス
松本彩果, PANTO Laura, 杉之下景介, 小柳香奈子, 渡邉日出海, 日本分子生物学会年会プログラム・要旨集(Web), 43rd, 2020年

哺乳類の胎生において重要な免疫調節遺伝子の由来に関する研究
網中希羽子, 小柳香奈子, 渡邉日出海, 日本進化学会大会プログラム・講演要旨集(Web), 21st, 2019年

概日リズム形成機構構成遺伝子の機能獲得進化過程の推定
佐賀野ひかる, 小柳香奈子, 渡邉日出海, 日本進化学会大会プログラム・講演要旨集(Web), 21st, 2019年

乳糖分解酵素(ラクターゼ)活性持続症関連遺伝子の探索
島橋拓也, 小柳香奈子, 渡邉日出海, 日本分子生物学会年会プログラム・要旨集(Web), 41st, ROMBUNNO.1LBA‐020 (WEB ONLY), 2018年
日本語

Human mastadenovirusにおける尿道炎発症に関わるサイトの探索
飯田 雅, 花岡 希, 藤本 嗣人, 伊藤 晋, 出口 隆, 安田 満, 小柳 香奈子, 渡邉 日出海, 日本性感染症学会誌, 28, 2, 202, 202, 2017年11月
(一社)日本性感染症学会, 日本語

全北区において隔離分布するダイセツタカネヒカゲOeneis melissaの種分化過程に関する研究
富岡駿, 井上望太郎, 小柳香奈子, 渡邉日出海, 日本進化学会大会プログラム・講演要旨集(Web), 19th, 112 (WEB ONLY), 2017年08月24日
日本語

Human mastadenovirusにおける流行性角結膜炎原因アミノ酸サイトの探索
飯田雅, 小柳香奈子, 日隈陸太郎, 青木功喜, 渡邉日出海, 日本化学療法学会雑誌, 65, Supplement-A, 379, 379, 2017年03月03日
(一社)日本感染症学会, 日本語

アデノウイルス咽頭扁桃炎の迅速検査による後方視的検討
高橋 健一郎, 花岡 希, 田村 まり子, 志田 洋子, 安田 菜穂子, 渡邉 日出海, 鈴木 葉子, 藤本 嗣人, 杉原 茂孝, 感染症学雑誌, 90, 臨増, 370, 370, 2016年03月
(一社)日本感染症学会, 日本語

エラーの統計的特性に基づく高出力シークエンシングシステムからの出力におけるエラー処理法の開発
青木慧斗, 小柳香奈子, 渡邉日出海, 日本分子生物学会年会プログラム・要旨集(Web), 39th, ROMBUNNO.2P‐0888 (WEB ONLY), 2016年
日本語

鳥類進化において歯の喪失をもたらした可能性のある遺伝的変化に関する研究
小松篤史, 小柳香奈子, 渡邉日出海, 日本分子生物学会年会プログラム・要旨集(Web), 39th, ROMBUNNO.3LBA‐006 (WEB ONLY), 2016年
日本語

ブートストラップ法に基づく組換えゲノム領域同定法の開発
西宮航, 小柳香奈子, 渡邉日出海, 日本分子生物学会年会プログラム・要旨集(Web), 39th, ROMBUNNO.2P‐0892 (WEB ONLY), 2016年
日本語

不活化ポリオワクチンの有効性・安全性の検証及び国内外で進められている新規腸管ウイルスワクチン開発に関する研究 日本および世界で流行しているエンテロウイルス71のサブジェノグループとその活用法に関する検討
藤本嗣人, 花岡希, 加納和彦, 椎野禎一郎, 荻美貴, 牧野友彦, 小長谷昌未, 橋爪芽衣, 渡邉日出海, 志田洋子, 鈴木葉子, 不活化ポリオワクチンの有効性・安全性の検証及び国内外で進められている新規腸管ウイルスワクチン開発に関する研究 平成26年度 総括・分担研究報告書, 52‐55, 2015年
日本語

ヒトアデノウイルス8型と54型の分子遺伝学的起源の検討
北市伸義, 北市伸義, 北市伸義, 北市伸義, 山根翔太郎, ゴンザレス ガブリエル, パント ローラ, 奥山雄一郎, 金子久俊, 青木功喜, 小柳香奈子, 渡邉日出海, 日本眼感染症学会・日本眼炎症学会・日本コンタクトレンズ学会総会・日本涙道・涙液学会プログラム・講演抄録集, 52nd-49th-58th-4th, 67, 2015年
日本語

ヒトABO対立遺伝子頻度の民族間差発生過程に関する研究
加地一貴, 小柳香奈子, 渡邉日出海, 日本分子生物学会年会プログラム・要旨集(Web), 37th, 2P-0134 (WEB ONLY), 2014年
日本語

サウジアラビアにおいて流行性角結膜炎患者から採取されたヒトアデノウイルスの由来に関する研究
奥山雄一郎, 山根翔太郎, ゴンザレス ガブリエル, パントー ラウラ, タバラ ハーリド, 金子久俊, 小柳香奈子, 青木功喜, 渡邉日出海, 日本分子生物学会年会プログラム・要旨集(Web), 37th, 3P-0724 (WEB ONLY), 2014年
日本語

結膜炎患者の眼から分離されたアデノウイルスD種48,60,および65型(候補株)のリコンビナント型の新しいアデノウイルス
藤本嗣人, 小川知子, 花岡希, 小倉惇, 堀田千恵美, 仁和岳史, GONZALEZ Gabriel, 渡邉日出海, 日本ウイルス学会学術集会プログラム・抄録集, 61st, 193, 2013年10月29日
日本語

近縁種ゲノム配列を用いたヒトゲノム配列未決定領域の塩基配列決定
福尾悠平, 山根翔太郎, 小柳香奈子, 渡邉日出海, 情報処理学会研究報告(CD-ROM), 2011, 6, ROMBUNNO.BIO-28,NO.6, 2012年04月15日
日本語

近縁種ゲノム配列を用いたヒトゲノム配列未決定領域の塩基配列決定
福尾 悠平, 山根 翔太郎, 小柳 香奈子, 渡邉 日出海, 情報処理学会研究報告. BIO, バイオ情報学, 2012, 6, 1, 2, 2012年03月21日
ヒトゲノムプロジェクトは2004年に完了し、解読されたヒトゲノム配列は広く利用されている。しかしながら現在でもユークロマチン領域に関しても1%程度が配列未決定領域として残されている。一方でヒトゲノム上にマッピングされないヒトcDNA配列が存在しており、機能既知の遺伝子が未だ配列未決定領域内に存在することが示唆される。本研究ではヒトに近縁な霊長類のゲノム配列を利用することで、ヒトゲノム配列未決定領域の塩基配列決定を行った。, 一般社団法人情報処理学会, 日本語

顕微鏡画像を用いたSVDDによる深海底生物の分類体系の推定法 (メディア工学 ヒューマンインフォメーション 映像表現&コンピュータグラフィックス)
長谷川 尭史, 小川 貴弘, 渡邉 日出海, 映像情報メディア学会技術報告, 36, 9, 73, 78, 2012年02月13日
映像情報メディア学会, 日本語

SVDDを用いた顕微鏡画像からの新種深海底生物の検出および分類体系上の位置の推定法
長谷川尭史, 小川貴弘, 渡邉日出海, 長谷山美紀, 映像情報メディア学会誌(Web), 66, 7, 2012年

SVDDを用いた顕微鏡画像からの新種深海底生物の検出および分類体系上の位置の推定法
長谷川 尭史, 小川 貴弘, 渡邉 日出海, 長谷山 美紀, The Journal of The Institute of Image Information and Television Engineers, 66, 7, J240, J250, 2012年
This paper presents a support vector data description (SVDD)-based method for finding new benthic species from microscopic images and its application to taxonomy position estimation. First, the proposed method generates hyperspheres that represent taxonomic species taxa of known species and enables automatic species classification. Furthermore, weight estimation of visual features based on multiple kernel learning (MKL) is used in this approach to realize automatic weighting of categorical traits that are traditionally determined by taxonomists. Next, based on the traditional taxonomic clas..., The Institute of Image Information and Television Engineers, 日本語

脳の左右非対称性に関連する遺伝子群の発現制御領域に関する解析
田尻鮎美, 小柳香奈子, 渡邉日出海, 日本分子生物学会年会プログラム・要旨集(Web), 35th, WEB ONLY 3P-0026, 2012年
日本語

バッテリー駆動による2000m級小型ROVの開発と運用
山本潤, 岩森利弘, 星直樹, 坂岡桂一郎, 高木省吾, 沼本修, 阪幸宏, 有村博紀, 渡邉日出海, 日本水産学会大会講演要旨集, 2011, 10, 2011年09月28日
日本語

比較ゲノム解析による新型アデノウイルス54型の進化過程の検討
青木功喜, 北市伸義, 北市伸義, 石田晋, 石古博昭, 金子久俊, 渡邉日出海, 小柳香奈子, ゴンザレス ガブリエル, 大野重昭, 日本眼科学会雑誌, 115, 臨増, 202, 202, 2011年04月15日
(公財)日本眼科学会, 日本語

顕微鏡画像中に含まれる底生生物の自動分類法 : SVDDを用いた分類の高精度化に関する検討(ITS画像処理,映像メディア,視覚及び一般)
長谷川 尭史, 小川 貴弘, 渡邉 日出海, 長谷山 美紀, 映像情報メディア学会技術報告, 35, 9, 125, 129, 2011年02月14日
本文では,Support Vector Data Description(SVDD)を用いた顕微鏡画像中に含まれる生物の自動分類法を提案する.提案手法では,数種類の底生生物の画像を対象としてSVDDを用いた学習を行い,生成された識別器を用いて実際に撮像した顕微鏡画像中に含まれる生物の生物種分類を行う.このとき,SVDDの識別のみでは一度に多くの生物種を高精度に分類することは困難であるため,階層的な分岐処理を導入する.具体的に高精度に識別可能な生物種を順次取り除き生物種を絞り込むことで,複数の生物種を扱った場合でもより高精度な分類を行うことを可能とする., 一般社団法人映像情報メディア学会, 日本語

顕微鏡画像中に含まれる底生生物の自動分類法―SVDDを用いた分類の高精度化に関する検討―
長谷川尭史, 小川貴弘, 渡邉日出海, 長谷山美紀, 電子情報通信学会技術研究報告, 110, 421(IE2010 104-144), 125, 129, 2011年02月14日
日本語

複数の生物情報源の利用によるイネの有用形質関連遺伝子の推定
鈴木拓幸, 渡邉日出海, 小柳香奈子, 天野直己, 日本分子生物学会年会プログラム・要旨集(Web), 34th, WEB ONLY 2P-0274, 2011年
日本語

生命の起源につながる原始地球環境下での化学物質反応系の推定
石丸貴史, 小柳香奈子, 渡邉日出海, 生化学, ROMBUNNO.1P-1162, 2010年
日本語

木構造アライメントを用いた大規模機能アノテーション法の開発
伊藤真純, 小柳香奈子, 渡邉日出海, 生化学, 83回・33回, ROMBUNNO.4T19-1, 1, 2010年
(公社)日本生化学会, 日本語

補完的投票に基づくオプティカルフローのロバスト推定
FANG Ming, 高氏秀則, 金子俊一, 渡邉日出海, 画像電子学会誌, 39, 5, 714, 724, 2010年
A novel robust method of estimating optical flow for a dynamic image sequence with poor quality is proposed. In order to estimate the optical flow, in a neighborhood of each interest position, we divide the local region into some sub-regions and then compute the similarity profile for each sub-region by using Orientation Code Matching. These similarity profiles around the position can be used to extract two kinds of voting: positive voting (candidate vectors) and negative voting (suppressing areas). The positive voting can be used to enhance the signal corresponding to the correct optical flows, and the negative voting can be used to reduce noises corresponding to incorrect optical flows. These two votings are integrated into complementary voting in order to extract a reasonable flow together with proper parameters which maximize the signal to noise ratio. The experiments with real image sequences are conducted to show the effectiveness of proposed method. © 2010, The Institute of Image Electronics Engineers of Japan. All rights reserved., 英語

生命系異分野共同研究プロジェクト
渡邉日出海, 金子俊一, 長谷山美紀, 電子情報通信学会誌, 92, 10, 822, 827, 2009年10月01日
一般社団法人電子情報通信学会, 日本語

補完的な投票処理に基づくロバストなオプティカルフロー計算
FANG Ming, 高氏秀則, 金子俊一, 渡邉日出海, 精密工学会大会学術講演会講演論文集, 2009, C17, 2009年02月25日
日本語

ゲノム育種による効率的品種育成技術の開発―多様性ゲノム解析研究―1 遺伝子配列情報比較を利用したイネ科作物の新規機能遺伝子の探索(2)比較ゲノム解析による穀類有用遺伝子の探索
伊藤剛, 沼寿隆, 田中剛, 渡邉日出海, 小柳香奈子, 農林水産省農林水産技術会議事務局研究成果, 474, 18, 20, 2009年02月20日
日本語

系統樹集合からの頻出分岐パターンの抽出と解析
伊藤真純, 渡邉日出海, 日本分子生物学会年会講演要旨集, 32nd, Late-Breaking Abstracts, 29, 2009年
日本語

地理的隔離を引き起こした大陸分断の年代情報に基づく種分岐年代の推定
竹下和貴, 小柳香奈子, 渡邉日出海, 日本進化学会大会プログラム・講演要旨集(Web), 10th, 2008年

重複遺伝子間の遺伝子変換の同定および機能進化への影響の解明
原雄一郎, 小柳香奈子, 渡邉日出海, 生化学, 81回・31回, 1T2-9, 9, 2008年
(公社)日本生化学会, 日本語

タンパク質の相同性情報に基づく進化ドメイン抽出法の開発
伊藤真純, 岩田浩明, 小柳香奈子, 渡邉日出海, 生化学, 4P-0957, 2008年
日本語

生物の進化・多様性をもたらしたゲノム情報解明へ 1.ヒトへの進化のゲノム基盤,ヒト・霊長類の比較ゲノム解析
渡邉日出海, 藤山秋佐夫, 実験医学, 25, 2, 226, 231, 2007年02月01日
日本語

ヒトゲノム内機能的特徴領域の検出
谷口陽介, 小柳香奈子, 渡邉日出海, 生化学, 4P-1267, 2007年
日本語

系統関係を考慮した縮重プライマー(degenerate primer)設計法の開発
池田勝志, 小柳香奈子, 渡邉日出海, 生化学, 3P-1218, 2007年
日本語

[Chimpanzee genome sequencing and comparative analysis with the human genome].
Watanabe H, Hattori M, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme, 51, 178, 187, 2006年02月
2

ゲノム情報 チンパンジーゲノム概要版配列の解読
渡邉 日出海, 服部 正平, 蛋白質核酸酵素, 51, 2, 178, 187, 2006年02月
共立出版, 日本語

RNA新大陸,発見!転写産物で浮かびあがるヒトゲノムの特徴
小柳香奈子, 渡辺日出海, バイオニクス, 3, 1, 36, 41, 2006年01月01日
日本語

哺乳類ゲノム中の遺伝子クラスタの進化における遺伝子変換の役割
原雄一郎, 小柳香奈子, 渡邉日出海, 日本進化学会大会プログラム・講演要旨集(Web), 7th, 2005年

相同遺伝子群の進化に対する局所的遺伝子重複の寄与に関する比較ゲノム解析
原雄一郎, 小柳香奈子, 渡辺日出海, 日本分子生物学会年会プログラム・講演要旨集, 27th, 839, 2004年11月25日
日本語

ヘテロ三量体Gタンパク質介在シグナル伝達系の多様化の獲得免疫系成立への寄与に関する分子進化解析
工藤充, 小柳香奈子, 金谷重彦, 渡辺日出海, 日本分子生物学会年会プログラム・講演要旨集, 27th, 841, 2004年11月25日
日本語

ヒト化のゲノム論--チンパンジーとヒトの比較ゲノム (特集 進化学研究の新世紀--生命の多様性と統合化) -- (進化学の成果)
渡邉 日出海, 科学, 74, 10, 1220, 1226, 2004年10月
岩波書店, 日本語

ヒト/チンパンジーY染色体の比較ゲノム解析―チンパンジーY染色体の物理地図作製―
黒木陽子, TAYLOR T D, 豊田敦, 伊藤武彦, 渡辺日出海, 山田智之, 森下真一, PARK H‐S, 稲垣尚美, 日本分子生物学会年会プログラム・講演要旨集, 26th, 801, 2003年11月25日
日本語

Construction of a physical map for human-chimpanzee Y chromosome comparative analysis.
Y Kuroki, TD Taylor, A Toyoda, H Watanabe, T Yamada, S Morishita, T Itoh, M Hattori, Y Sakaki, A Fujiyama, AMERICAN JOURNAL OF HUMAN GENETICS, 73, 5, 440, 440, 2003年11月
UNIV CHICAGO PRESS, 英語, 研究発表ペーパー・要旨（国際会議）

[Introduction to comparative genomics].
Watanabe H, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme, 48, 849, 856, 2003年06月
7

あなたにも役立つバイオインフォマティクス2(9)比較ゲノムから何がわかるのか
渡邉 日出海, 蛋白質核酸酵素, 48, 7, 849, 856, 2003年06月
共立出版, 日本語

[Construction and analysis of a human-chimpanzee comparative clone map].
Watanabe H, Hattori M, Fujiyama A, Sakaki Y, Tanpakushitsu Kakusan Koso, 47, 7, 808, 813, 2002年06月

[Construction and analysis of a human-chimpanzee comparative clone map].
Watanabe H, Hattori M, Fujiyama A, Sakaki Y, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme, 47, 808, 813, 2002年06月
7

ゲノム情報 ヒト・チンパンジー比較ゲノム地図
渡邉 日出海, 藤山 秋佐夫, 服部 正平, 蛋白質核酸酵素, 47, 7, 808, 813, 2002年06月
共立出版, 日本語

Chimpanzee genome project for understanding ourselves
Y Sakaki, H Watanabe, A Fujiyama, M Hattori, A Toyoda, TD Taylor, GENOME SCIENCE: TOWARDS A NEW PARADIGM?, 1246, 183, 187, 2002年
Comparative genomics is a powerful approach to extract genetic information from large stretches of nucleotide sequences through identification of conserved regions that are most likely functionally important. Genomic information is also the most valuable resources for understanding genetic differences between the species. Comparison between humans and chimpanzees is the most efficient and effective approach to understand what makes us human. Since chimpanzees are our closest relatives, the differences between us are fewer and these differences are more likely important. As the first step, we presented a first generation human-chimpanzee comparative genome map. The map was constructed through paired alignment of 77,461 chimpanzee BAC-end sequences (BESs) with human genomic sequences obtained from international DNA databanks. By using the BESs mapped with high confidence, the difference between the chimpanzee and human genomes was calculated to be 1.23% at the nucleotide level. This value is consistent with previous observations. The comparative map revealed not only base substations, but also a considerable number of rearrangements which have taken place during evolution. Based on the map, the sequencing of the chimpanzee genome was initiated and its preliminary data were shown including the sequence of FOXP2 gene related to speech and language. (C) 2002 Published by Elsevier Science B.V., ELSEVIER SCIENCE BV, 英語

ゲノム解析のための情報処理と進化学 (特集 バイオインフォマティクス)
渡邉 日出海, エストレ-ラ, 0, 88, 18, 23, 2001年07月
統計情報研究開発センタ-, 日本語

Sequencing and comparative analysis of 1.5 Mb of Down syndrome critical region in human chromosome 21 and mouse chromosome 16
A Toyoda, M Hattori, HS Park, TD Taylor, H Watanabe, T Yada, Y Totoki, A Fujiyama, Y Sakaki, R Reeves, CYTOGENETICS AND CELL GENETICS, 92, 1-2, 21, 21, 2001年
KARGER, 英語, 研究発表ペーパー・要旨（国際会議）

DNA sequence and comparative genomics of human chromosome 21
Y Sakaki, M Hattori, A Fujiyama, A Toyoda, TD Taylor, H Watanabe, T Yada, HS Park, Y Totoki, R Reeves, CYTOGENETICS AND CELL GENETICS, 92, 1-2, 19, 20, 2001年
KARGER, 英語, 研究発表ペーパー・要旨（国際会議）

理研GSCゲノムシークエンスシステム 21番染色体の完成と11,18番のドラフトシークエンス
豊田敦, PARK H S, TAYLOR T D, 矢田哲士, 渡辺日出海, 十時泰, 藤山秋佐夫, 服部正平, 榊佳之, 日本分子生物学会年会プログラム・講演要旨集, 23rd, 317, 2000年11月25日
日本語

ゲノムDNA配列の種内・種間比較に基づくゲノム領域の機能および進化過程の推定
渡辺日出海, 豊田敦, 矢田哲士, 村上勝彦, 十時泰, 藤山秋佐夫, 服部正平, 高木利久, 榊佳之, 日本分子生物学会年会プログラム・講演要旨集, 23rd, 694, 2000年11月25日
日本語

[Determination of DNA sequence of the whole chromosome 21].
Sakaki Y, Hattori M, Toyoda A, Watanabe H, Yada T, Taylor T, Park HS, Totoki Y, Fujiyama A, Tanpakushitsu Kakusan Koso, 45, 15, 2520, 2527, 2000年11月

An automated system for sequence analysis, annotation, and comparison.
TD Taylor, H Watanabe, K Gun, J Sun, Y Sakaki, AMERICAN JOURNAL OF HUMAN GENETICS, 67, 4, 257, 257, 2000年10月
UNIV CHICAGO PRESS, 英語, 研究発表ペーパー・要旨（国際会議）

Erratum: The DNA sequence of human chromosome 21: The chromosome 21 mapping and sequencing consortium (Nature (2000) 405 (311-319))
M. Hattori, A. Fujiyama, T. D. Taylor, H. Watanabe, T. Yada, H. S. Park, A. Toyoda, K. Ishll, Y. Totoki, D. K. Choi, Y. Groner, E. Soeda, M. Ohki, T. Takagi, Y. Sakaki, S. Taudlen, K. Blechschmidt, A. Polley, U. Menzel, J. Delabar, K. Kumpf, R. Lehmann, D. Patterson, K. Reichwald, A. Rump, M. Schillhabel, A. Schudy, W. Zimmermann, A. Rosenthal, J. Kudoh, K. Schibuya, K. Kawasaki, S. Asakawa, A. Shintani, T. Sasaki, K. Nagamine, S. Mitsuyama, S. E. Antonarakis, S. Minoshima, N. Shimizu, G. Nordsiek, K. Hornischer, P. Brant, M. Scharfe, O. Schon, A. Desario, J. Relchelt, G. Kauer, H. Blocker, J. Ramser, A. Beck, S. Klages, S. Hennig, L. Riesselmann, E. Dagand, T. Haaf, S. Wehrmeyer, K. Borzym, K. Gardiner, D. Nizetic, F. Francis, H. Lehrach, R. Reinhardt, M. L. Yaspo, Nature, 407, 110, 2000年09月07日

The DNA sequence of human chromosome 21 (vol 405, pg 311, 2000)
M Hattori, A Fujiyama, TD Taylor, H Watanabe, T Yada, HS Park, A Toyoda, K Ishii, Y Totoki, DK Choi, Y Groner, E Soeda, M Ohki, T Takagi, Y Sakaki, S Taudien, K Blechschmidt, A Polley, U Menzel, J Delabar, K Kumpf, R Lehmann, D Patterson, K Reichwald, A Rump, M Schillhabel, A Schudy, W Zimmermann, A Rosenthal, J Kudoh, K Schibuya, K Kawasaki, S Asakawa, A Shintani, T Sasaki, K Nagamine, S Mitsuyama, SE Antonarakis, S Minoshima, N Shimizu, G Nordsiek, K Hornischer, P Brant, M Scharfe, O Schon, A Desario, J Reichelt, G Kauer, H Blocker, J Ramser, A Beck, S Klages, S Hennig, L Riesselmann, E Dagand, T Haaf, S Wehrmeyer, K Borzym, K Gardiner, D Nizetic, F Francis, H Lehrach, R Reinhardt, ML Yaspo, NATURE, 407, 6800, 110, 110, 2000年09月
MACMILLAN PUBLISHERS LTD, 英語, その他

ゲノム進化 解読ゲノムの分析から何がわかったのか? ヒト21番染色体の構造と進化　　　　　　　　　　　　　　　
渡邉 日出海, 服部 正平, 藤山 秋佐夫, Taylor Todd D, 矢田 哲士, 朴 洪石, 豊田 敦, 石井 一夫, 十時 泰, 崔 東國, 生化学, 72, 8, 627, 627, 2000年08月
(公社)日本生化学会, 日本語

共通祖先から全生物への進化史が明らかになる (特集 ヒトゲノムからみた新しい生命観・人間観)
渡邉 日出海, 科学, 70, 4, 346, 353, 2000年04月
岩波書店, 日本語

ヒト21番染色体21q22.1(D21S226‐SOD‐AML)の連続した6Mb領域のゲノムシーケンシング
石井一夫, 豊田敦, TAYLOR T, PARK H‐S, 矢田哲士, 十時泰, 渡辺日出海, 宇山希, 榊佳之, 日本分子生物学会年会プログラム・講演要旨集, 22nd, 522, 1999年11月22日
日本語

ヒトゲノムシーケンシング総合支援システム
矢田哲士, TAYLOR T D, 渡辺日出海, 十時泰, 服部正平, 伊藤武彦, 川越千晴, 高木利久, 榊佳之, 日本分子生物学会年会プログラム・講演要旨集, 22nd, 289, 1999年11月22日
日本語

生物配列解析プログラムYEBISEN
十時泰, 矢田哲士, TAYLOR T D, 渡辺日出海, 高木利久, 榊佳之, 日本分子生物学会年会プログラム・講演要旨集, 22nd, 289, 1999年11月22日
日本語

比較ゲノム解析に基づいたゲノム領域の機能推定
渡辺日出海, TAYLOR T D, 矢田哲士, 十時泰, 高木利久, 榊佳之, 日本分子生物学会年会プログラム・講演要旨集, 22nd, 289, 1999年11月22日
日本語

Bacterial features in the genome of Methanococcus jannaschii in terms of gene composition and biased base composition in ORFs and their surrounding regions (vol 205, pg 7, 1997)
H Watanabe, T Gojobori, KI Miura, GENE, 213, 1-2, 219, 219, 1998年06月
ELSEVIER SCIENCE BV, 英語, その他

大腸菌における転写制御関係の進化に関する研究
渡辺 日出海, 森 健太郎, 日本分子生物学会年会プログラム・講演要旨集, 19, 0, 452, 452, 1996年08月01日
日本語

アミノ酸配列の類似性による大腸菌ORFのグループ及び他種バクテリアとの比較
伊藤 剛, 竹本 経緯子, 矢野 実, 松田 秀雄, 渡辺 日出海, 森 浩禎, 日本分子生物学会年会プログラム・講演要旨集, 19, 0, 740, 740, 1996年08月01日
日本語

EVOLUTION OF GENOME STRUCTURE IN ESCHERICHIA COLI PRESUMED ON THE BASIS OF THE DISTRIBUTION OF HOMOLOGOUS GENES IN THE GENOME
WATANABE H., GOJOBORI T., The Japanese journal of genetics, 70, 6, 751, 751, 1995年12月01日
英語

ヒトアデノウイルスの進化　　　　　　　　　　　　　　　
渡邉 日出海
第24回日本アデノウイルス研究会, 2024年07月06日, 口頭発表（招待・特別）
2024年07月06日 - 2024年07月06日, ［招待講演］, ［国際会議］

1999年 - 現在
日本進化学会　　　　　　　　　　　　　　　

予防を科学する炎症細胞社会学
科学研究費助成事業 新学術領域研究(研究領域提案型)
2022年04月01日 - 2023年03月31日
松島 綱治, 池尾 一穂, 渡邉 日出海
日本学術振興会, 新学術領域研究(研究領域提案型), 東京理科大学, 22H04906

単一細胞シークエンスデータに基づく細胞社会学のための情報手法の開発とデータ解析
科学研究費補助金(新学術領域研究(研究領域提案型))
2017年 - 2021年
池尾 一穂
単一細胞データポータルを構築し、領域内研究グループから収集したデータをの解析を行い、その全データをダウンロード・表示できる形でまとめ公開した。
細胞集団の動態モデルの構築に向けて、１細胞レベルの体細胞変異パターンを用いて、既知の知識と矛盾のない細胞系譜を推定できることを示した。また、従来の機械学習方法を見直し、より少ない細胞の発現データから、遺伝子の相互作用や共発現に関する有用な情報を抽出するための数学的手法の開発に成功した。機械学習モデルを用いて、APA破綻遺伝子リストのエンリッチ解析から疾患関連遺伝子抽出を可能とした。
文部科学省, 新学術領域研究(研究領域提案型), 国立遺伝学研究所, 競争的資金, 17H06399

ゲノムアダプテーションのシステム的理解
科学研究費助成事業 新学術領域研究(研究領域提案型)
2010年04月01日 - 2016年03月31日
篠原 彰, 石井 俊輔, 井澤 毅, 渡邉 日出海, 石井 浩二郎, 岩崎 博史, 岡田 由紀, 白髭 克彦, 伊藤 武彦
減数分裂では組換えにより、父親、母親由来のゲノム情報の混ぜ合せが起こるだけでなく、”新規のゲノム変動”が配偶子に生じ、それが次世代の表現型に影響を与えること（ゲノムアダプテーション）が近年知られつつある。このようなゲノムアダプテーションを介して、ゲノムの多様性が生物集団の中に生じ、長期的には新しいゲノムを生み出す言動力になっていると考えられている。本新学術領域はゲノムアダプテーションの分子レベルでの仕組みを明らかにすること、様々な生物で見られる特異的ゲノムアダプテーション現象を解析する、ゲノムアダプテーションを解析するツールを開発すること、を目的としていた。平成22年度に開始した本領域研究は２６年度が最終年度にあたる。本新学術領域の研究の進展を図ると共に、研究成果をまとめることが大切になる。特に、異分野の研究者が十分な連携の元で研究を推進した成果をまとめため、総括班が非常に重要な役割を担っている。過去５年間のまとめは、２６年度末に行った。さらに新学術のまとめを行うため、評価のための資料を作成し、ヒアリウングを受け、A-の評価を得た。また、最終国際シンポジウムとして、平成２８年３月１日から３日まで、淡路島夢舞台国際会議場で、新しくできた新学術領域“染色体OS”(代表、東大白髭克彦)と合同で開催した。外国人招待講演者に加え、若手の１０名の発表を行った。
日本学術振興会, 新学術領域研究(研究領域提案型), 大阪大学, 22125001

ゲノム配列解析に基づく突然変異発生特性と適応進化の解明
科学研究費補助金(新学術領域研究(研究領域提案型))
2010年 - 2014年
渡邉 日出海
本申請研究では、ゲノム領域における突然変異率の直接計測法を開発し、分子進化解析に基づく適応進化関連領域の検出を可能にすることを目指す。また、その有効性を確かめるために、塩基配列決定を伴うゲノム解析を実施する。初めに、本領域において解析されている酵母実験株の次世代シーケンサーによる配列決定データを用いて、既に公開されている酵母ゲノムとの比較解析を行い、重点的に解析すべき領域の選定を進めた。また、並行してそれらの酵母実験株を至適条件下で継代培養するための実験環境を整え、試験的培養を始めている。一方、本研究課題と密接に関連する新規の研究として、札幌において長年流行性角結膜炎(EKC)患者から採取されているヒトアデノウイルス(HAdV)のゲノム解析(配列決定と比較解析)を開始した。HAdV-D群の血清型8,19,37,54の採取時期の異なる計7ゲノム、および、HAdV-E群の血清型4の1ゲノムを新たに配列決定している。これまでの解析の結果、異系統ゲノム間での組換えが特定領域で高頻度に起きていることと、それらの領域がエピトープ関連領域を含んでおり組換えに正の選択がかかっている可能性があることなどが明らかになった。そこで、酵母の場合と同様に、アデノウイルスゲノムの各領域におけるゲノム間組換えの起こりやすさを計測し、EKCの新たな流行とおそらく密接に関連すると考えられる真の正の選択領域を明...
文部科学省, 新学術領域研究(研究領域提案型), 北海道大学, 研究代表者, 競争的資金, 22125009

地質学情報と遺伝情報の比較解析に基づく生物進化史の解明
科学研究費補助金(基盤研究(B))
2006年 - 2008年
渡邉 日出海
生物種の分岐年代を高精度で推定するために、従来広く利用されてきた化石試料には依存しない方法を新たに開発した。本方法では、生物学とは独立に年代が詳しく調べられている地殻変動イベントとそれによって引き起こされたと考えられる種分化を基準とする。これにより、化石試料に伴う大きな曖昧さを回避し、化石を得ることが困難な系統についても現生生物のDNAを用いて種分岐年代を正確に求めることができるようになった。
文部科学省, 基盤研究(B), 北海道大学->東京大学->北海道大学, 研究代表者, 競争的資金, 18370095

比較ゲノム解析に基づくヒト固有遺伝情報の同定と機能推定
科学研究費補助金(特定領域研究)
2006年 - 2007年
渡邉 日出海, 小柳 香奈子
本研究課題の目的は、ヒト固有形質に密接に関連すると推定されるヒト固有遺伝情報を同定することである。この目的のために、ヒトとチンパンジーの種分岐後にヒトゲノムに生じたヒト固有遺伝情報ならびにヒト特異的進化状態を示すゲノム領域の同定を行った。まず、基盤となるデータとして、ヒト-チンパンジー一マカク間の高精度なゲノム直系領域多重アラインメントの作成を行った。具体的には、曖昧なゲノム領域の実験による確認、ゲノム概要配列に加えてBACクローン配列を用いた解析、詳細な分子進化学的解析によるゲノム直系領域の推定を行った。次にこのゲノムアラインメントに基づき、ヒト系統に特異的な、挿入・欠失および塩基置換・アミノ酸置換速度変化を同定した。特に、従来は解析が困難であるために対象外とされていた、ヒトとチンパンジーの種分岐後に遺伝子重複が起きた遺伝子群についても解析を行った。その結果、ヒト固有形質に関連する候補遺伝子が推定された。これら候補遺伝子のさらなる機能解析等により、ヒト固有形質の理解が進むことが期待される。上記の研究過程では、プログラムによる自動処理に加えて、人間の目によるデータの精査も重要となる。そこで、このデータ精査を支援するための解析ツールの開発も行った。このツールは、長大なゲノム間の対応領域を可視化し、それを自由に拡大縮小したり、対応領域の各ゲノム上における位置情報や塩基相違度等の必...
文部科学省, 特定領域研究, 北海道大学, 研究代表者, 競争的資金, 18017002

比較ゲノム解析に基づくヒト固有遺伝情報の同定と機能推定
科学研究費補助金(特定領域研究)
2005年 - 2005年
渡邉 日出海
新たにゲノム比較解析アルゴリズムとツールを開発し、これまでの科研費で構築してきたPCクラスタを活用して、ヒトゲノム完成配列データとチンパンジー概要配列データの間の高精度アラインメントを作成し、両ゲノム間の相違に関する詳細なデータを作成した。次に、両ゲノム間の違いのうちどれがヒトゲノムで生じた変化によるものなのかを明らかにするために、米国で実施されているマカクゲノムの全ゲノムショットガン配列決定によるデータを用いた比較解析を実施した。まず、最優先領域として遺伝子領域に対する詳細な解析を行った。その結果、Ensemb1データベースでアノテーションが付されている遺伝子約33,000個のうち、7,836個の遺伝子でヒト特異的領域が見出され、そのうち443個の遺伝子において、CDS領域内挿入・欠失が見つかった。2つの嗅覚受容体遺伝子は全体がヒト特異的領域として検出され、それらが偽遺伝子であるという証拠は示されていない。これまでは、霊長類において嗅覚受容体遺伝子が多数偽遺伝子化したりプロセスト偽遺伝子が挿入されたりしている例が報告されているが、新規に嗅覚受容体遺伝子がヒトにおいて生じたのであれば、大変興味深い。443個の遺伝子のうち、270個についてはOMIMデータが存在しており、それらについて、他の様々なデータを併せて詳細な解析を進めている。イントロンやUTR、遺伝子外領域においても多...
文部科学省, 特定領域研究, 北海道大学, 研究代表者, 競争的資金, 17018002

ゲノム進化の地球史との対比に基づく生物進化史の解明
科学研究費補助金(基盤研究(C))
2003年 - 2005年
渡邉 日出海
ヒトを含む霊長類の種分岐年代や分岐過程、原因などについて種々の仮説が立てられているが、未だ議論が絶えない。そこで、総合研究大学院大学の颯田助教授と、テキサス大学ヒューストンヘルスサイエンスセンターの印南秀樹博士と共同で、ヒトとチンパンジーのゲノム配列データならびにその他の霊長類の付加的データを集団遺伝学的に比較解析し、ヒト-チンパンジー間等の霊長類の種分岐をできるだけ詳細に推定することを試みた。これらの研究においては、チンパンジーゲノム全体から無作為に抽出した断片配列データ(合計は0.6%に相当)とその各々に対応するヒトゲノムデータを用いて集団遺伝学的解析を行い、ヒトとチンパンジーの最終共通祖先集団のサイズ、種分岐の開始から完了までにかかった時間とその年代をできるだけ慎重にかつ詳細に推定した。その結果、最終共通祖先の有効集団サイズは1万程度になり、また種分岐は極めて短期間のうちに完了したという推定結果が得られた。この結果は、従来から行われていた単純なモデルによる祖先集団サイズの推定と一致することから、霊長類・ヒトの進化過程についてこれまで提唱されてきたいくつかの説を限定することができる。類人猿進化に関しても、ヒトと、ゴリラ、オランウータン、旧世界ザル、新世界ザルの間の種分岐年代はそれぞれおよそ、720、1,800、3,400、6,500万年前と推定された。特に古い推定値につい...
文部科学省, 基盤研究(C), 奈良先端科学技術大学院大学->北海道大学, 研究代表者, 競争的資金, 15510158

ゲノム配列の種間・種内比較に基づく進化過程の推定
科学研究費補助金(特定領域研究)
2004年 - 2004年
渡邉 日出海, 小柳 香奈子
理化学研究所が中心となって日独中韓台の9センターで編成したコンソーシアムにおいて、霊長類の染色体としては世界で初めてのチンパンジー22番染色体(PTR22)の完成配列を決定し、Nature誌のArticleとして発表した。この論文において本研究代表者は比較解析全般を担当し、ヒト相同染色体であるヒト21番染色体(HSA21)および他の類人猿との間で種間比較解析を行った。本研究の目的は、500-700万年前にヒトとチンパンジーが分岐した後に、それぞれの系統において生じてきたゲノムの構造変化の詳細を明らかにすることである。同コンソーシアムによる先行研究(Fujiyama et al.,2002)において両ゲノムは塩基配列レベルで平均1.23%の塩基置換が起きていることをあきらかにしていたが、PTR22-HSA21間では若干高い1.44%の平均塩基置換率になっていた。これは主としてテロメア側半分ではGC含量が高くCpGのメチル化脱アミノ化による塩基置換(C:G→T:A)が高頻度で起こっていることによることがわかった。他に、PTR22はHSA21よりも約1%小さいこと、多くの挿入・欠失が存在し短いものほど頻度が高いこと、300bp以上の長さの挿入は大部分が散在性反復配列の挿入によるものであること、挿入はHSA21で高頻度で起こっている一方、欠失は両染色体で完全に同じ傾向をしめしているこ...
文部科学省, 特定領域研究, 奈良先端科学技術大学院大学->北海道大学, 研究代表者, 競争的資金, 16011239

ゲノム配列の種間・種内比較に基づく進化過程の推定
科学研究費補助金(特定領域研究)
2003年 - 2003年
渡邉 日出海
国際コンソーシアムにおいて、類人猿あるいは霊長類の染色体としては世界で初めてチンパンジーの22番染色体(PTR22)の完成配列を決定し、そのヒト相同染色体であるヒト21番染色体(HSA21)との間で種間比較を行った。本研究の目的は、ヒトとチンパンジーの染色体塩基配列を比較することによって、約500万年前にヒトとチンパンジーが分岐した後に、それぞれの系統において生じてきたゲノムの構造変化の詳細を明らかにすることである。両ゲノムは塩基配列レベルでは僅かに1.23%程度しか異なっていないことを同コンソーシアムが先行研究(Fujiyama et al.,2002)で明らかにしていたため、概要配列ではなく高精度の完成配列の形でチンパンジーゲノム配列の決定を行うことが必要であると考えられた。しかし、そのためには膨大な作業が必要になるため、まず染色体レベルでの解析を行うことにし、同様のメンバーで構成された国際コンソーシアムによってその完成配列が決定されたヒト21番染色体(Hattori et al.,2000)の相同染色体を解析の対象に選んだ。配列決定の結果、(1)PTR22はHSA21よりも約1%小さい、(2)多くの挿入・欠失(INDEL)が存在し、短いものほど頻度が高い、(3)300bp以上の長さの挿入は、大部分が散在性反復配列の挿入によるものである、(4)HSA21、PTR22それぞ...
文部科学省, 特定領域研究, 奈良先端科学技術大学院大学, 研究代表者, 競争的資金, 15011238

ゲノム配列の種間・種内比較に基づく進化過程の推定
科学研究費補助金(特定領域研究)
2002年 - 2002年
渡邉 日出海
本研究課題において、2つの研究を具体的に行った。ツェツェバエの細胞内共生微生物であるWigglesworthia glossinidiaのゲノムを他の共同研究者と共に決定し、そのゲノム配列を、本研究代表者らが既に決定し報告してあったアブラムシの細胞内共生微生物であるBuchnera APSのゲノム配列(Shigenobu, et al.,2000)と比較し、共生微生物の進化過程についての様々な情報を得た(Akman, et al.,2002)。Buchneraのゲノムは、共生生物としては世界で初めて配列決定されたものであったため、その解析によって明らかになった様々な特徴が共生生物の特徴であると我々は考えた。しかし、系統的にBuchneraに極めて近い関係にあると考えられているWigglesworthiaのゲノムと比較してみた結果、予想に反して、多くの点で異なっていることが明らかになった。例えば、これら2つのゲノムは最も小さい部類に属しているため、その中に存在する遺伝子は生存にとって必要不可欠なものに限られているであろうと考えられていたが、実際には、2者に共通している遺伝子は僅かに7割弱であった。したがって、生物は一定の生活環境に置かれると、その環境に適応するかたちで短期間のうちにゲノムの中身が大きく変わることが明らかになった。もう1つの研究は、チンパンジー22番染色体(PTR...
文部科学省, 特定領域研究, 理化学研究所->奈良先端科学技術大学院大学, 研究代表者, 競争的資金, 14011260

ゲノムDNA配列の種内・種間比較に基づくゲノム領域の機能および進化過程の推定
科学研究費補助金(特定領域研究(C))
2001年 - 2001年
渡邉 日出海
本課題においては、平成12年度の特定領域研究(C)の同名課題において開発を行ったシステムを用いて、ヒトやマウスを含む様々な真核生物と原核生物のゲノムDNA配列データを国際データベースなどから定期的に収集し、ヒトゲノムに対して種内・種間の大規模比較解析を行った。その結果、ヒトゲノム内におびただしい数の重複領域が見出され、その分布はランダムではなく、例えば、セントロメア近傍領域に集中して見られるといった様々な特徴が明らかにされた。このような特徴は、核内における染色体の局在性や染色体間の位置関係などについての示唆を与えている。また、ヒトゲノム配列内に存在するヒト固有遺伝情報を発見するために、ヒトに最も近い種であるチンパンジーのゲノム配列決定の第一段階としてチンパンジーBACクローンマッピングを行った。このマッピングでは、64,116個のチンパンジーBACクローンの両端配列(BES)のみを決め、その配列をヒトゲノム配列と比較することによって、各チンパンジークローンの物理位置を正確に推定するという、これまでに無い独自の方法を採用した。このマッピングの結果から、ヒトゲノムとチンパンジーゲノムとの間にこれまで知られていたものも含む多くの大規模な構造の違いが見出され、また、BESの詳細な比較解析とPCRを用いた解析から、ヒトゲノム内の変わりやすい領域、高度に保存している領域、ヒト固有領域を見...
文部科学省, 特定領域研究(C), 理化学研究所, 研究代表者, 競争的資金, 13202076

ゲノムDNA配列の種内・種間比較に基づくゲノム領域の機能および進化過程の推定
科学研究費補助金(特定領域研究(C))
2000年 - 2000年
渡邉 日出海
初めに、大量のゲノムDNA配列を短時間で比較するために、備品として購入したAlphaStation DS20E上に、最新のゲノムDNA配列データを公共データベースから定期的に自動で収集管理するシステムを構築した。この自動データ収集システムを用いて、ヒト、類人猿、霊長類、マウスなどを含むその他の哺乳類、ニワトリ、アフリカツメガエル、フグ、ショウジョウバエ、線虫、酵母、植物等の、真核生物のゲノムデータを定期的に収集し種毎に整理する。現在のところ、ヒトを除いた脊椎動物に限った場合、800メガ塩基対相当のデータが蓄積されている。この収集されたゲノムDNA配列データを種内・種間で高速で自動比較するために、配列データを一旦加工した後、BLASTを用いて総当りの比較を行い、保存領域に関する情報を蓄積するシステムを構築した。比較解析データには、保存領域に関する、配列、保存度、ゲノム上あるは配列データ上での位置と方向などが含まれる。比較解析結果から生物学的意味を抽出するために、まず、保存領域を含む遺伝子に関する情報をゲノムデータから抽出する。遺伝子に関する情報には、遺伝子内での位置、エクソン/イントロンの区別、遺伝子の機能が含まれる。保存領域の、遺伝子との関係を見ることにより、保存領域が持つ機能の範囲を限定する。続いて、保存領域の中から、遺伝子内に見出されないもの、つまり遺伝子によって機能が限...
文部科学省, 特定領域研究(C), 理化学研究所, 研究代表者, 競争的資金, 12202058

Associate Editor　　　　　　　　　　　　　　　
2009年01月01日
Oxford University Press
Genome Biology and Evolution
［新聞・雑誌］