Researcher Database

Hidemi Watanabe
Faculty of Information Science and Technology Bioengineering and Bioinformatics Bioinformatics
Professor

Researcher Profile and Settings

Affiliation

  • Faculty of Information Science and Technology Bioengineering and Bioinformatics Bioinformatics

Job Title

  • Professor

J-Global ID

Research Interests

  • ゲノム比較解析   比較解析   チンパンジーゲノム   チンパンジー   ヒト   ヒトゲノム   ゲノム進化   ヒト固有形質   ヒト固有遺伝情報   免疫系   種分化   染色体   分子進化   系統特異性   生物進化   地理的隔離   マッピング   非重複遺伝子   突然変異率   比較ゲノム   有効集団サイズ   大量情報処理   真核生物   地球史   ヒト特異的遺伝情報   継代培養   組換え   origins of life   comparative genomics   evolution   genome   

Research Areas

  • Life sciences / Evolutionary biology
  • Life sciences / Genomics
  • Life sciences / Virology

Academic & Professional Experience

  • 2004/04 - Today 北海道大学 大学院・情報科学研究科 教授
  • 2002/07 - 2004/03 National Institute of Informatics
  • 2002/04 - 2004/03 理化学研究所 ゲノム科学総合研究センター 客員主管研究員
  • 2002/04 - 2004/03 Nara Institute of Science and Technology Graduate School of Information Science
  • 1999/05 - 2002/03 理化学研究所 ゲノム科学総合研究センター
  • 1997/05 - 1999/04 National Center for Biotechnology Information, National Institutes of Health
  • 1995/04 - 1997/03 National Institute of Genetics

Association Memberships

  • Society of Evolutionary Studies, Japan   The Society for the Study of the Origin and Evolution of Life Japan   The American Association for the Advancement of Science (AAAS)   The Society for Molecular Biology and Evolution (SMBE)   

Research Activities

Published Papers

  • Gabriel Gonzalez, Camden R. Bair, Daryl M. Lamson, Hidemi Watanabe, Laura Panto, Michael J. Carr, Adriana E. Kajon
    Virology 538 11 - 23 2019 [Refereed][Not invited]
     
    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.
  • Marcin Jakalski, Kazutaka Takeshita, Mathieu Deblieck, Kanako O. Koyanagi, Izabela Makalowska, Hidemi Watanabe, Wojciech Makalowski
    BIOLOGY DIRECT 11 1745-6150 2016/08 [Refereed][Not invited]
     
    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.
  • Gabriel Gonzalez, Kanako O. Koyanagi, Koki Aoki, Hidemi Watanabe
    JOURNAL OF VIROLOGY 89 (12) 6209 - 6217 0022-538X 2015/06 [Refereed][Not invited]
     
    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.
  • Takatoshi Abe, Hidemi Watanabe, Kanako O. Koyanagi, Botaro Inoue
    GENOME 58 (5) 185 - 185 0831-2796 2015/05 [Refereed][Not invited]
  • 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 1344-6304 2014/09 [Refereed][Not invited]
  • Gabriel Gonzalez, Kanako O. Koyanagi, Koki Aoki, Nobuyoshi Kitaichi, Shigeaki Ohno, Hisatoshi Kaneko, Susumu Ishida, Hidemi Watanabe
    GENE 547 (1) 10 - 17 0378-1119 2014/08 [Refereed][Not invited]
     
    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.
  • 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 1344-6304 2014/07 [Refereed][Not invited]
     
    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.
  • Koki Aoki, Hisatosi Kaneko, Nobuyoshi Kitaichi, Hidemi Watanabe, Susumu Ishida, Shigeaki Ohno
    Nippon Ganka Gakkai Zasshi 117 (9) 721 - 726 2013/09 [Refereed][Not invited]
     
    Human adenovirus causing epidemic keratoconjunctivitis is limited to D and E species. Recent progress of bioinformatics revealed that these viruses attach to the host with fiber, infiltrate to the host cells via RGD motif of penton base, and show their serological reaction by hexon. Loop 1 and 2 are the variable region of hexon. The recombination of above three hot spots introduces the novel types such as HAdV-53, -54, and -56. Boinformatics may promise the rapid genotyping in the case of nosocomial infection, predicting the future epidemic, and the estimate of the therapeutic target molecules in the near future.
  • Jun YAMAMOTO, Toshihiro IWAMORI, Naoki HOSHI, Takuzo ABE, Keiichiro SAKAOKA, Yoshihiko KAMEI, Shogo TAKAGI, Osamu NUMAMOTO, Yukihiro SAKA, Kazuhisa SUEOKA, Hiroki ARIMURA, Hidemi WATANABE
    Journal of Fisheries Technology 5 (2) 171 - 174 2013/02 [Refereed][Not invited]
     
    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.
  • 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 0022-538X 2013/01 [Refereed][Not invited]
  • 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 2150-7511 2012/09 [Refereed][Not invited]
     
    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.
  • HASEGAWA TAKASHI, OGAWA TAKAHIRO, WATANABE HIDEMI, HASEYAMA MIKI
    電子情報通信学会技術研究報告 111 (442(IE2011 105-132)) 73 - 78 0913-5685 2012/02 [Not refereed][Not invited]
  • Atsuko Yamada, Kanako O. Koyanagi, Hidemi Watanabe
    GENE 491 (2) 232 - 236 0378-1119 2012/01 [Refereed][Not invited]
     
    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.
  • 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 0022-1317 2011/06 [Refereed][Not invited]
     
    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.
  • 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 0095-1137 2011/02 [Refereed][Not invited]
     
    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.
  • WATANABE Hidemi, KANEKO Shun'ichi, HASEYAMA Miki
    The Journal of the Institute of Electronics, Information, and Communication Engineers 一般社団法人電子情報通信学会 92 (10) 822 - 827 0913-5693 2009/10 [Not refereed][Not invited]
  • Masumi Itoh, Hidemi Watanabe
    BIOINFORMATICS 25 (7) 958 - 959 1367-4803 2009/04 [Refereed][Not invited]
     
    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.
  • H Innan, H Watanabe
    MOLECULAR BIOLOGY AND EVOLUTION 23 (5) 1040 - 1047 0737-4038 2006/05 [Refereed][Not invited]
     
    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.
  • Y Satta, M Hickerson, H Watanabe, C O'hUigin, J Klein
    JOURNAL OF MOLECULAR EVOLUTION 59 (4) 478 - 487 0022-2844 2004/10 [Refereed][Not invited]
     
    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.
  • FS Collins, ES Lander, J Rogers, RH Waterston
    NATURE 431 (7011) 931 - 945 0028-0836 2004/10 [Refereed][Invited]
     
    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.
  • 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 0028-0836 2004/05 [Refereed][Not invited]
     
    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.
  • Y Yamada, H Watanabe, F Miura, H Soejima, M Uchiyama, T Iwasaka, T Mukai, Y Sakaki, T Ito
    GENOME RESEARCH 14 (2) 247 - 266 1088-9051 2004/02 [Refereed][Not invited]
     
    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 0091-7451 2003 [Refereed][Not invited]
  • L Akman, A Yamashita, H Watanabe, K Oshima, T Shiba, M Hattori, S Aksoy
    NATURE GENETICS 32 (3) 402 - 407 1061-4036 2002/11 [Refereed][Not invited]
     
    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.
  • 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 0036-8075 2002/01 [Refereed][Not invited]
     
    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.
  • 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 Miura
    JOURNAL OF BIOCHEMISTRY 129 (6) 851 - 860 0021-924X 2001/06 [Refereed][Not invited]
     
    Nucleotide sequences around the boundaries of all open reading frames in the Escherichia coli whole genome were analyzed, Characteristic base biases were observed after the initiation codon and before the termination codon. We examined the effect of the base sequence after the initiation codon on the translation efficiency, by introducing mutations after the initiation codon of the E. coli dihydrofolate reductase (DHFR) gene, considering codon and base biases, and using in vitro and in vivo translation systems. In both assay systems, the two most frequent second codons, AAA and AAU, enhanced the translation efficiency compared with the wild type, whereas the effects of lower frequency codons were not significant. Experiments using 16S rRNA variants with mutations in the putative complementary sequence to the region downstream of the initiation codon showed that the translation efficiency of none of the DHFR mutants was affected. These results demonstrate that the statistically most frequent sequences for the second codon enhance translation efficiency, and this effect seems to be independent of base pairing between mRNA and 16S rRNA.
  • 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 0028-0836 2001/02 [Refereed][Not invited]
     
    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.
  • Shigenobu S, Watanabe H, Sakaki Y, Ishikawa H
    J Mol Evol 53 (4/5) 377 - 386 0022-2844 2001 [Refereed][Not invited]
  • 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  0028-0836 2000/09/07 [Not refereed][Not invited]
  • S Shigenobu, H Watanabe, M Hattori, Y Sakaki, H Ishikawa
    NATURE 407 (6800) 81 - 86 0028-0836 2000/09 [Refereed][Not invited]
     
    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.
  • 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 1340-2838 2000/06 [Refereed][Not invited]
     
    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.
  • 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 0028-0836 2000/05 [Refereed][Not invited]
     
    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.
  • MI Bellgard, T Itoh, H Watanabe, T Imanishi, T Gojobori
    MOLECULAR STRATEGIES IN BIOLOGICAL EVOLUTION 870 293 - 300 0077-8923 1999 [Refereed][Not invited]
     
    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.
  • H Watanabea, T Gojobori, K Miura
    GENE 205 (1-2) 7 - 18 0378-1119 1997/12 [Refereed][Not invited]
     
    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 [Refereed][Not invited]
  • Tateno Y, Ikeo K, Imanishi T, Watanabe H, Endo T, Yamaguchi Y, Suzuki Y, Takahashi K, Tsunoyama K, Kawai M, Kawanishi Y, Naitou K, Gojobori T
    J Mol Evol 44 (Suppl 1) S38 - S43 1997 [Refereed][Not invited]
  • Watanabe H, Mori H, Itoh T, Gojobori T
    J Mol Evol 44 (Suppl 1) S57 - S64 1997 [Refereed][Not invited]
  • J Otsuka, H Watanabe, KT Mori
    JOURNAL OF THEORETICAL BIOLOGY 178 (2) 183 - 204 0022-5193 1996/01 [Refereed][Not invited]
     
    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 0266-7061 1995/04 [Refereed][Not invited]
     
    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.
  • 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 1990/06 [Refereed][Not invited]

MISC

Awards & Honors

  • 2017/09 日本学術振興会 審査委員表彰
  • 2012/06 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 
    受賞者: 方 明;髙氏 秀則;金子 俊一;渡邉 日出海
  • 2001/11 The fourth international workshop on advanced genomics The 3rd poster award

Research Grants & Projects

  • 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
    文部科学省:科学研究費補助金(新学術領域研究(研究領域提案型))
    Date (from‐to) : 2017 -2021 
    Author : 池尾 一穂
  • 文部科学省:科学研究費補助金(新学術領域研究(研究領域提案型))
    Date (from‐to) : 2010 -2014 
    Author : 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...
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2006 -2008 
    Author : Watanabe WATANABE
     
    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:科学研究費補助金(特定領域研究)
    Date (from‐to) : 2006 -2007 
    Author : 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:科学研究費補助金(特定領域研究)
    Date (from‐to) : 2005 -2005 
    Author : 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...
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 2003 -2005 
    Author : Hidemi WATANABE
     
    To address the issue on the speciation process in the primate lineages, several studies were conducted with collaborators, Dr.Satta at Sokendai, and Dr.Innan at the University of Texas Health Science Center at Houston, with large numbers of sequence fragments randomly selected from the chimpanzee genome and the human genome as well as additional data sets of other primates. In these studies, the ancestral population sizes of primates and the divergence times of major primate lineages were carefully estimated, and it was suggested that the ancestral population sizes of primates were several ...
  • 文部科学省:科学研究費補助金(特定領域研究)
    Date (from‐to) : 2004 -2004 
    Author : 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:科学研究費補助金(特定領域研究)
    Date (from‐to) : 2003 -2003 
    Author : 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:科学研究費補助金(特定領域研究)
    Date (from‐to) : 2002 -2002 
    Author : 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:科学研究費補助金(特定領域研究(C))
    Date (from‐to) : 2001 -2001 
    Author : 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:科学研究費補助金(特定領域研究(C))
    Date (from‐to) : 2000 -2000 
    Author : 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...

Educational Activities

Teaching Experience

  • Bioengineering
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 情報科学研究科
    キーワード : 遺伝情報, genetic information, バイオインフォマティクス, bioinformatics, イメージング, imaging, 生体医工学, biomedical engineering, 細胞力学, cell mechanics
  • Inter-Graduate School Classes(General Subject):Inter-Disciplinary Sciences
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
  • Genome Informatics
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 情報科学研究科
    キーワード : ゲノム, 複製, 転写, 翻訳, 塩基配列決定, 分子進化解析, ゲノム配列解析, ゲノム発現解析
  • Bioengineering
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 情報科学研究科
    キーワード : 遺伝情報, genetic information, バイオインフォマティクス, bioinformatics, イメージング, imaging, 生体医工学, biomedical engineering, 細胞力学, cell mechanics
  • Genome Informatics
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 情報科学研究科
    キーワード : ゲノム, 複製, 転写, 翻訳, 塩基配列決定, 分子進化解析, ゲノム配列解析, ゲノム発現解析
  • Biochemistry
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 工学部
    キーワード : アミノ酸、タンパク質、糖、脂質、核酸、酵素、反応速度、生体エネルギー、代謝
  • Bioinformatics
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 工学部
    キーワード : 遺伝情報、ゲノム、染色体、遺伝子、遺伝子型、表現型、突然変異、メンデル遺伝学、分子進化
  • Molecular Biology I
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 工学部
    キーワード : 遺伝情報、ゲノム、染色体、遺伝子、遺伝子型、表現型、突然変異、メンデル遺伝学、分子進化
  • Molecular Biology I
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 工学部
    キーワード : アミノ酸、タンパク質、糖、脂質、核酸、酵素、反応速度、生体エネルギー、代謝
  • Molecular Biology II
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 工学部
    キーワード : 遺伝情報、ゲノム、染色体、遺伝子、遺伝子型、表現型、突然変異、メンデル遺伝学、分子進化

Committee Membership

  • 2016/07 - Today   International Committee on Taxonomy of Viruses   Adenoviridae Study Group
  • 2009/01 - Today   Society for Molecular Biology and Evolution   An Associate Editor of Genome Biology and Evolution

Social Contribution

Social Contribution

Media Coverage

  • Associate Editor
    Date : 2009/01/01
    Publisher, broadcasting station: Oxford University Press
    Program, newspaper magazine: Genome Biology and Evolution
    Paper

Others

  • 2017/09 -2017/09 日本学術振興会表彰
    科研費審査における有意義な審査意見を付し公正・公平な審査に大きく貢献したことに対する表彰


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