MF研究者総覧

研究者データベース

詳細
小柳　香奈子(コヤナギ　カナコ)
情報科学研究院　生命人間情報科学部門　バイオインフォマティクス分野
准教授
researchmap個人ページ
Last Updated :2024/05/09

基本情報

所属

  • 情報科学研究院　生命人間情報科学部門　バイオインフォマティクス分野

職名

  • 准教授

学位

  • 博士（理学）（京都大学）

ホームページURL

J-Global ID

研究キーワード

  • 系統解析   エピジェネティクス   細胞系譜   細胞分化   イネ   ヒト   ウイルス   比較ゲノム解析   ゲノム構造   発現制御   分子進化   進化   ゲノム   

研究分野

  • ライフサイエンス / システムゲノム科学
  • ライフサイエンス / 進化生物学
  • ライフサイエンス / ゲノム生物学

職歴

  • 2019年 - 現在 北海道大学 大学院情報科学研究院 准教授
  • 2007年 - 2019年 北海道大学 大学院情報科学研究科 准教授
  • 2004年 - 2007年 北海道大学 大学院情報科学研究科 助教授
  • 2003年 - 2004年 奈良先端科学技術大学院大学 情報科学研究科 助手
  • 2001年 - 2003年 生物情報解析研究センター 特別研究員
  • 2000年 - 2001年 京都大学 大学院理学研究科 派遣研究員

研究活動情報

論文

  • Kanako O Koyanagi
    BMC research notes 16 1 222 - 222 2023年09月19日 
    OBJECTIVE: Diversification of cell types and changes in epigenetic states during cell differentiation processes are important for understanding development. Recently, phylogenetic analysis using DNA methylation and histone modification information has been shown useful for inferring these processes. The purpose of this study was to examine whether chromatin accessibility data can help infer these processes in murine hematopoiesis. RESULTS: Chromatin accessibility data could partially infer the hematopoietic differentiation hierarchy. Furthermore, based on the ancestral state estimation of internal nodes, the open/closed chromatin states of differentiating progenitor cells could be predicted with a specificity of 0.86-0.99 and sensitivity of 0.29-0.72. These results suggest that the phylogenetic analysis of chromatin accessibility could offer important information on cell differentiation, particularly for organisms from which progenitor cells are difficult to obtain.
  • Nozomi Saito, Sunlu Chen, Katsuya Kitajima, Zhitong Zhou, Yohei Koide, Jaymee R Encabo, Maria Genaleen Q Diaz, Il-Ryong Choi, Kanako O Koyanagi, Yuji Kishima
    Frontiers in plant science 14 1261705 - 1261705 2023年 
    INTRODUCTION: Rice genomes contain endogenous viral elements homologous to rice tungro bacilliform virus (RTBV) from the pararetrovirus family Caulimoviridae. These viral elements, known as endogenous RTBV-like sequences (eRTBVLs), comprise five subfamilies, eRTBVL-A, -B, -C, -D, and -X. Four subfamilies (A, B, C, and X) are present to a limited degree in the genomes of the Asian cultivated rice Oryza sativa (spp. japonica and indica) and the closely related wild species Oryza rufipogon. METHODS: The eRTBVL-D sequences are widely distributed within these and other Oryza AA-genome species. Fifteen eRTBVL-D segments identified in the japonica (Nipponbare) genome occur mostly at orthologous chromosomal positions in other AA-genome species. The eRTBVL-D sequences were inserted into the genomes just before speciation of the AA-genome species. RESULTS AND DISCUSSION: Ten eRTBVL-D segments are located at six loci, which were used for our evolutionary analyses during the speciation of the AA-genome species. The degree of genetic differentiation varied among the eRTBVL-D segments. Of the six loci, three showed phylogenetic trees consistent with the standard speciation pattern (SSP) of the AA-genome species (Type A), and the other three represented phylogenies different from the SSP (Type B). The atypical phylogenetic trees for the Type B loci revealed chromosome region-specific evolution among the AA-genome species that is associated with phylogenetic incongruences: complex genome rearrangements between eRTBVL-D segments, an introgression between the distant species, and low genetic diversity of a shared eRTBVL-D segment. Using eRTBVL-D as an indicator, this study revealed the phylogenetic incongruence of local chromosomal regions with different topologies that developed during speciation.
  • Sunao Sugita, Yoshihiko Usui, Hidemi Watanabe, Laura Panto, Miyabi Iida, Keisuke Suginoshita, Kanako O Koyanagi, Akihiro Nishida, Yasuo Kurimoto, Masayo Takahashi, Tatsuya Shindo, Hiroaki Nishioka, Masahiko Takano, Takeshi Kezuka, Hiroshi Goto, Nobuyoshi Kitaichi
    Ophthalmology 130 4 443 - 445 2022年12月23日 [査読有り]
  • Fujino Kenji, Kawahara Yoshihiro, Koyanagi Kanako O., Shirasawa Kenta
    Breeding Science 71 2 125 - 133 日本育種学会 2021年 [査読有り]
     

    Understanding genetic diversity among local populations is a primary goal of modern crop breeding programs. Here, we demonstrated the genetic relationships of rice varieties in Hokkaido, Japan, one of the northern limits of rice cultivation around the world. Furthermore, artificial selection during rice breeding programs has been characterized using genome sequences. We utilized 8,565 single nucleotide polymorphisms and insertion/deletion markers distributed across the genome in genotype-by-sequencing for genetic diversity analyses. Phylogenetics, genetic population structure, and principal component analysis showed that a total of 110 varieties were classified into four distinct clusters according to different populations geographically and historically. Furthermore, the genome sequences of 19 rice varieties along with historic representations in Hokkaido, nucleotide diversity and FST values in each cluster revealed that artificial selection of elite phenotypes focused on chromosomal regions. These results clearly demonstrated the history of the selections on agronomic traits as genome sequences among current rice varieties from Hokkaido.

  • Kanako O. Koyanagi
    Gene 721S 100021 - 100021 2019年09月 [査読有り][通常論文]
     
    Revealing the landscape of epigenetic changes in cells during differentiation is important for understanding the development of organisms. In this study, to infer such epigenetic changes during human hematopoiesis, ancestral state estimation based on a phylogenetic tree was applied to map the epigenomic changes in six kinds of histone modifications onto the hierarchical cell differentiation process of hematopoiesis using epigenomes of eight types of differentiated hematopoietic cells. The histone modification changes inferred during hematopoiesis showed that changes that occurred on the branches separating different cell types reflected the characteristics of hematopoiesis in terms of genomic position and gene function. These results suggested that ancestral state estimation based on phylogenetic analysis of histone modifications in differentiated hematopoietic cells could reconstruct an appropriate landscape of histone modification changes during hematopoiesis. Since integration of the inferred changes of different histone modifications could reveal genes with specific histone marks such as active histone marks and bivalent histone marks on each internal branch of cell-type trees, this approach could provide valuable information for understanding the cell differentiation steps of each cell lineage.
  • Ayami Matsushima, Jun Sese, Kanako O. Koyanagi
    ChemBioChem 20 16 2054 - 2058 2019年08月16日 [査読有り][通常論文]
     
    Endomorphins are neuropeptides that bind strongly to μ-opioid receptors and are considered to play important roles in pain modulation and other biological functions. Two endomorphins have been identified, to date, endomorphine-1 and -2; both are tetrapeptides and differ by only a single amino acid in the third position. Both peptides were isolated from bovine brains; however, their precursor genes have not been identified. In this study, a nucleotide sequence corresponding to the endomorphin-1 peptide in an expressed sequence tag database has been found and a preproendomorphin-like precursor peptide from human brain complementary DNA (cDNA) has been cloned. The cDNA consists of nucleotide sequences of two already annotated predicted genes, and the putative peptide differs by one amino acid from the isolated endomorphin peptides. It is proposed herein that there is the possibility of unknown short proteins or peptide precursors being missed by automated gene prediction programs based on similarities of known protein sequences. A novel concept of how to produce endomorphins from a similar peptide is described. The oxidatively modified base might provide a clue for understanding discrepancies between nucleotide sequences on the genome and those on cDNAs.
  • Marcin Jakalski, Kazutaka Takeshita, Mathieu Deblieck, Kanako O. Koyanagi, Izabela Makałowska, Hidemi Watanabe, Wojciech Makałowski
    Biology Direct 11 1 35 - 35 2016年08月04日 [査読有り][通常論文]
     
    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.
  • FUJINO Kenji, OBARA Mari, SHIMIZU Toshiaki, KOYANAGI Kanako O., IKEGAYA Tomohito
    Breeding Science 65 5 403 - 410 2015年12月19日 [査読有り][通常論文]
     
    Plant breeding programs in local regions may generate genetic variations that are desirable to local populations and shape adaptability during the establishment of local populations. To elucidate genetic bases for this process, we proposed a new approach for identifying the genetic bases for the traits improved during rice breeding programs; association mapping focusing on a local population. In the present study, we performed association mapping focusing on a local rice population, consisting of 63 varieties, in Hokkaido, the northernmost region of Japan and one of the northern limits of rice cultivation worldwide. Six and seventeen QTLs were identified for heading date and low temperature germinability, respectively. Of these, 13 were novel QTLs in this population and 10 corresponded to the QTLs previously reported based on QTL mapping. The identification of QTLs for traits in local populations including elite varieties may lead to a better understanding of the genetic bases of elite traits. This is of direct relevance for plant breeding programs in local regions.
  • Takatoshi Abe, Hidemi Watanabe, Kanako O. Koyanagi, Botaro Inoue
    GENOME 58 5 185 - 185 2015年05月 [査読有り][通常論文]
  • Kanako O. Koyanagi
    Genome Biology and Evolution 7 3 699 - 705 2015年03月 [査読有り][通常論文]
     
    How cells divide and differentiate is a fundamental question in organismal development; however, the discovery of differentiation processes in various cell types is laborious and sometimes impossible. Phylogenetic analysis is typically used to reconstruct evolutionary processes based on inherent characters. It could also be used to reconstruct developmental processes based on the developmental changes that occur during cell proliferation and differentiation. In this study, DNA methylation information from differentiated hematopoietic cells was used to perform phylogenetic analyses. The results were assessed for their validity in inferring hierarchical differentiation processes of hematopoietic cells and DNA methylation processes of differentiating progenitor cells. Overall, phylogenetic analyses based on DNA methylation information facilitated inferences regarding hematopoiesis.
  • Gabriel Gonzalez, Kanako O. Koyanagi, Koki Aoki, Hidemi Watanabe
    Journal of Virology 89 12 6209 - 6217 2015年 [査読有り][通常論文]
     
    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.
  • Sunlu Chen, Ruifang Liu, Kanako O. Koyanagi, Yuji Kishima
    Virology 471-473 141 - 152 2014年12月01日 [査読有り][通常論文]
     
    Viral fossils in rice genomes are a best entity to understand ancient pararetrovirus activities through host plant history because of our advanced knowledge of the genomes and evolutionary history with rice and its related species. Here, we explored organization, geographic origins and genealogy of rice pararetroviruses, which were turned into endogenous rice tungro bacilliform virus-like (eRTBVL) sequences. About 300 eRTBVL sequences from three representative rice genomes were clearly classified into six families. Most of the endogenization events of the eRTBVLs were initiated before differentiation of the rice progenitor (> 160,000 years ago). We successfully followed the genealogy of old relic viruses during rice speciation, and inferred the geographical origins for these viruses. Possible virus genomic sequences were explained mostly by recombinations between different virus families. Interestingly, we discovered that only a few recombination events among the numerous occasions had determined the virus genealogy.
  • 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 2014年09月 [査読有り][通常論文]
  • Gabriel Gonzalez, Kanako O. Koyanagi, Koki Aoki, Nobuyoshi Kitaichi, Shigeaki Ohno, Hisatoshi Kaneko, Susumu Ishida, Hidemi Watanabe
    Gene 547 1 10 - 17 2014年08月15日 [査読有り][通常論文]
     
    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 ). 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. © 2014 Elsevier B.V. S
  • 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 2014年 [査読有り][通常論文]
     
    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 (HAdVD). 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 98z, 99z, 95z and 98z 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.
  • Kanako O Koyanagi, Tadashi Imanishi, Takashi Gojobori
    eLS. John Wiley & Sons, Ltd: Chichester 2013年12月 [査読有り][招待有り]
  • 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 2013年01月 [査読有り][通常論文]
  • Ruifang Liu, Kanako O. Koyanagi, Sunlu Chen, Yuji Kishima
    Plant Journal 72 5 817 - 828 2012年12月 [査読有り][通常論文]
     
    In plant genomes, the incorporation of DNA segments is not a common method of artificial gene transfer. Nevertheless, various segments of pararetroviruses have been found in plant genomes in recent decades. The rice genome contains a number of segments of endogenous rice tungro bacilliform virus-like sequences (ERTBVs), many of which are present between AT dinucleotide repeats (ATrs). Comparison of genomic sequences between two closely related rice subspecies, japonica and indica, allowed us to verify the preferential insertion of ERTBVs into ATrs. In addition to ERTBVs, the comparative analyses showed that ATrs occasionally incorporate repeat sequences including transposable elements, and a wide range of other sequences. Besides the known genomic sequences, the insertion sequences also represented DNAs of unclear origins together with ERTBVs, suggesting that ATrs have integrated episomal DNAs that would have been suspended in the nucleus. Such insertion DNAs might be trapped by ATrs in the genome in a host-dependent manner. Conversely, other simple mono- and dinucleotide sequence repeats (SSR) were less frequently involved in insertion events relative to ATrs. Therefore, ATrs could be regarded as hot spots of double-strand breaks that induce non-homologous end joining. The insertions within ATrs occasionally generated new gene-related sequences or involved structural modifications of existing genes. Likewise, in a comparison between Arabidopsis thaliana and Arabidopsis lyrata, the insertions preferred ATrs to other SSRs. Therefore ATrs in plant genomes could be considered as genomic dumping sites that have trapped various DNA molecules and may have exerted a powerful evolutionary force. © 2012 Blackwell Publishing Ltd.
  • Atsuko Yamada, Kanako O. Koyanagi, Hidemi Watanabe
    Gene 491 2 232 - 236 2012年01月10日 [査読有り][通常論文]
     
    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. © 2011 Elsevier B.V.
  • Koki Aoki, Maria Benkoe, Andrew J. Davison, Marcela Echavarria, Dean D. Erdman, Balazs Harrach, Adriana E. Kajon, David Schnurr, Goran Wadell
    JOURNAL OF VIROLOGY 85 11 5703 - 5704 2011年06月
  • 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 2011年06月 [査読有り][通常論文]
     
    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, 880249C 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 870006C 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. © 2011 SGM.
  • 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 2011年02月 [査読有り][通常論文]
     
    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. Copyright © 2011, American Society for Microbiology. All Rights Reserved.
  • Tsuyoshi Tanaka, Kanako O. Koyanagi, Takeshi Itoh
    Plant Physiology 149 3 1316 - 1324 2009年03月 [査読有り][通常論文]
     
    Alternative usage of transcription start sites (TSSs) is one of the key mechanisms to generate gene variation in eukaryotes. Here, we show diversified molecular evolution of TSSs in remotely related flowering plants, rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana), by comprehensive analyses of large collections of full-length cDNAs and genome sequences. We determined 45,917 representative TSSs within 23,445 loci of rice and 35,313 TSSs within 16,964 loci of Arabidopsis, about two TSSs per locus in either species. The nucleotide features around TSSs displayed distinct patterns when the most upstream TSSs were compared with downstream TSSs. We found that CG-skew and AT-skew were clearly different between upstream and downstream TSSs, and that this difference was commonly observed in rice and Arabidopsis. Relative entropy analysis revealed that the most upstream TSSs had retained canonical cis elements, whereas downstream TSSs showed atypical nucleotide features. Expression patterns were distinguishable between upstream and downstream TSSs. These results indicate that plant TSSs were generally diversified in downstream regions, resulting in the development of new gene expression patterns. Furthermore, our comparative analysis of TSS variation between the species showed a positive correlation between TSS number and gene conservation. Rice and Arabidopsis might have evolved novel TSSs in an independent manner, which led to diversification of these two species. © 2009 American Society of Plant Biologists.
  • Akihiro Matsuya, Ryuichi Sakate, Yoshihiro Kawahara, Kanako O. Koyanagi, Yoshiharu Sato, Yasuyuki Fujii, Chisato Yamasaki, Takuya Habara, Hajime Nakaoka, Fusano Todokoro, Kaori Yamaguchi, Toshinori Endo, Satoshi Oota, Wojciech Makalowski, Kazuho Ikeo, Yoshiyuki Suzuki, Kousuke Hanada, Katsuyuki Hashimoto, Momoki Hirai, Hisakazu Iwama, Naruya Saitou, Aiko T. Hiraki, Lihua Jin, Yayoi Kaneko, Masako Kanno, Katsuhiko Murakami, Akiko Ogura Noda, Naomi Saichi, Ryoko Sanbonmatsu, Mami Suzuki, Jun Ichi Takeda, Masayuki Tanaka, Takashi Gojobori, Tadashi Imanishi, Takeshi Itoh
    Nucleic Acids Research 36 SUPPL. 1 D787 - D792 2008年01月 [査読有り][通常論文]
     
    Orthologs are genes in different species that evolved from a common ancestral gene by speciation. Currently, with the rapid growth of transcriptome data of various species, more reliable orthology information is prerequisite for further studies. However, detection of orthologs could be erroneous if pairwise distance-based methods, such as reciprocal BLAST searches, are utilized. Thus, as a sub-database of H-InvDB, an integrated database of annotated human genes (http://h-invitational.jp/), we constructed a fully curated database of evolutionary features of human genes, called 'Evola'. In the process of the ortholog detection, computational analysis based on conserved genome synteny and transcript sequence similarity was followed by manual curation by researchers examining phylogenetic trees. In total, 18 968 human genes have orthologs among 11 vertebrates (chimpanzee, mouse, cow, chicken, zebrafish, etc.), either computationally detected or manually curated orthologs. Evola provides amino acid sequence alignments and phylogenetic trees of orthologs and homologs. In 'd / d view', natural selection on genes can be analyzed between human and other species. In 'Locus maps', all transcript variants and their exon/intron structures can be compared among orthologous gene loci. We expect the Evola to serve as a comprehensive and reliable database to be utilized in comparative analyses for obtaining new knowledge about human genes. © 2007 The Author(s). N S
  • Chisato Yamasaki, Katsuhiko Murakami, Yasuyuki Fujii, Yoshiharu Sato, Erimi Harada, Jun Ichi Takeda, Takayuki Taniya, Ryuichi Sakate, Shingo Kikugawa, Makoto Shimada, Motohiko Tanino, Kanako O. Koyanagi, Roberto A. Barrero, Craig Gough, Hong Woo Chun, Takuya Habara, Hideki Hanaoka, Yosuke Hayakawa, Phillip B. Hilton, Yayoi Kaneko, Masako Kanno, Yoshihiro Kawahara, Toshiyuki Kawamura, Akihiro Matsuya, Naoki Nagata, Kensaku Nishikata, Akiko Ogura Noda, Shin Nurimoto, Naomi Saichi, Hiroaki Sakai, Ryoko Sanbonmatsu, Rie Shiba, Mami Suzuki, Kazuhiko Takabayashi, Aiko Takahashi, Takuro Tamura, Masayuki Tanaka, Susumu Tanaka, Fusano Todokoro, Kaori Yamaguchi, Naoyuki Yamamoto, Toshihisa Okido, Jun Mashima, Aki Hashizume, Lihua Jin, Kyung Bum Lee, Yi Chueh Lin, Asami Nozaki, Katsunaga Sakai, Masahito Tada, Satoru Miyazaki, Takashi Makino, Hajime Ohyanagi, Naoki Osato, Nobuhiko Tanaka, Yoshiyuki Suzuki, Kazuho Ikeo, Naruya Saitou, Hideaki Sugawara, Claire O'Donovan, Tamara Kulikova, Eleanor Whitfield, Brian Halligan, Mary Shimoyama, Simon Twigger, Kei Yura, Kouichi Kimura, Tomohiro Yasuda, Tetsuo Nishikawa, Yutaka Akiyama, Chie Motono, Yuri Mukai, Hideki Nagasaki, Makiko Suwa, Paul Horton, Reiko Kikuno, Osamu Ohara, Doron Lancet, Eric Eveno, Esther Graudens, Sandrine Imbeaud, Marie Anne Debily, Yoshihide Hayashizaki, Clara Amid, Michael Han, Andreas Osanger, Toshinori Endo, Michael A. Thomas, Mika Hirakawa, Wojciech Makalowski, Mitsuteru Nakao, Nam Soon Kim, Hyang Sook Yoo, Sandro J. De Souza, Maria De Fatima Bonaldo, Yoshihito Niimura, Vladimir Kuryshev, Ingo Schupp, Stefan Wiemann, Matthew Bellgard
    Nucleic Acids Research 36 SUPPL. 1 D793 - D799 2008年01月 [査読有り][通常論文]
     
    Here we report the new features and improvements in our latest release of the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive annotation resource for human genes and transcripts. H-InvDB, originally developed as an integrated database of the human transcriptome based on extensive annotation of large sets of full-length cDNA (FLcDNA) clones, now provides annotation for 120 558 human mRNAs extracted from the International Nucleotide Sequence Databases (INSD), in addition to 54 978 human FLcDNAs, in the latest release H-InvDB_4.6. We mapped those human transcripts onto the human genome sequences (NCBI build 36.1) and determined 34 699 human gene clusters, which could define 34 057 (98.1%) protein-coding and 642 (1.9%) non-protein-coding loci; 858 (2.5%) transcribed loci overlapped with predicted pseudogenes. For all these transcripts and genes, we provide comprehensive annotation including gene structures, gene functions, alternative splicing variants, functional non-protein-coding RNAs, functional domains, predicted sub cellular localizations, metabolic pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite repeat motifs, co-localization with orphan diseases, gene expression profiles, orthologous genes, protein-protein interactions (PPI) and annotation for gene families. The current H-InvDB annotation resources consist of two main views: Transcript view and Locus view and eight sub-databases: the DiseaseInfo Viewer, H-ANGEL, the Clustering Viewer, G-integra, the TOPO Viewer, Evola, the PPI view and the Gene family/group. © 2007 The Author(s).
  • Tsuyoshi Tanaka, Baltazar A. Antonio, Shoshi Kikuchi, Takashi Matsumoto, Yoshiaki Nagamura, Hisataka Numa, Hiroaki Sakai, Jianzhong Wu, Takeshi Itoh, Takuji Sasaki, Ryo Aono, Yasuyuki Fujii, Takuya Habara, Erimi Harada, Masako Kanno, Yoshihiro Kawahara, Hiroaki Kawashima, Hiromi Kubooka, Akihiro Matsuya, Hajime Nakaoka, Naomi Saichi, Ryoko Sanbonmatsu, Yoshiharu Sato, Yuji Shinso, Mami Suzuki, Junichi Takeda, Motohiko Tanino, Fusano Todokoro, Kaori Yamaguchi, Naoyuki Yamamoto, Chisato Yamasaki, Tadashi Imanishi, Toshihisa Okido, Masahito Tada, Kazuho Ikeo, Yoshio Tateno, Takashi Gojobori, Yao Cheng Lin, Fu Jin Wei, Yueie Hsing, Qiang Zhao, Bin Han, Melissa R. Kramer, Richard W. McCombie, David Lonsdale, Claire C. O’donovan, Eleanor J. Whitfield, Rolf Apweiler, Kanako O. Koyanagi, Jitendra P. Khurana, Saurabh Raghuvanshi, Nagendra K. Singh, Akhilesh K. Tyagi, Georg Haberer, Masaki Fujisawa, Satomi Hosokawa, Yukiyo Ito, Hiroshi Ikawa, Michie Shibata, Mayu Yamamoto, Richard M. Bruskiewich, Douglas R. Hoen, Thomas E. Bureau, Nobukazu Namiki, Hajime Ohyanagi, Yasumichi Sakai, Satoshi Nobushima, Katsumi Sakata, Roberto A. Barrero, Yutaka Sato, Alexandre Souvorov, Brian Smith-White, Tatiana Tatusova, Suyoung An, Gynheung An, Satoshi Oota, Galina Fuks, Joachim Messing, Karen R. Christie, Damien Lieberherr, Hyeran Kim, Andrea Zuccolo, Rod A. Wing, Kan Nobuta, Pamela J. Green, Cheng Lu, Blake C. Meyers, Cristian Chaparro, Benoit Piegu, Olivier Panaud, Manuel Echeverria
    Nucleic Acids Research 36 SUPPL. 1 D1028 - 33 2008年01月01日 [査読有り][通常論文]
     
    The Rice Annotation Project Database (RAP-DB) was created to provide the genome sequence assembly of the International Rice Genome Sequencing Project (IRGSP), manually curated annotation of the sequence, and other genomics information that could be useful for comprehensive understanding of the rice biology. Since the last publication of the RAP-DB, the IRGSP genome has been revised and reassembled. In addition, a large number of rice-expressed sequence tags have been released, and functional genomics resources have been produced worldwide. Thus, we have thoroughly updated our genome annotation by manual curation of all the functional descriptions of rice genes. The latest version of the RAP-DB contains a variety of annotation data as follows: clone positions, structures and functions of 31 439 genes validated by cDNAs, RNA genes detected by massively parallel signature sequencing (MPSS) technology and sequence similarity, flanking sequences of mutant lines, transposable elements, etc. Other annotation data such as Gnomon can be displayed along with those of RAP for comparison. We have also developed a new keyword search system to allow the user to access useful information. The RAP-DB is available at: http://www.w3.org/1999/ http://rapdb.dna.affrc.go.jp/ and http://rapdb.lab.nig.ac.jp/. © 2007 The Author(s).
  • Hiroaki Sakai, Kanako O. Koyanagi, Tadashi Imanishi, Takeshi Itoh, Takashi Gojobori
    Gene 389 2 196 - 203 2007年03月15日 [査読有り][通常論文]
     
    Despite the wide distribution of processed pseudogenes in mammalian genomes, such as those of human and mouse, relatively little is known about their roles in genomic evolution. While gene duplications are recognized as one of the major driving forces in genome evolution, processed pseudogenes, which are retrotransposed copies of mRNAs, have been regarded as junk or selfish DNA for a long time. In order to elucidate the quantitative and qualitative contribution of processed pseudogenes to the mammalian genome evolution, we attempted to detect processed pseudogenes by extensively mapping the mRNAs to both the human and mouse genomes, and then we estimated the rate of their emergence. As a result, we revealed that the rate of pseudogene emergence was about 1-2% per gene per million years, which was as high as the rate (0.9%) of gene duplication in the human genome, although the rate of pseudogene emergence was found to drastically decrease in the hominid lineage. Furthermore, 1% of the processed pseudogenes seemed to be reinvigorated by post-retrotransposition transcription, many of them preserving the intact coding regions. Since the expression patterns of transcribed pseudogenes in various tissues were quite different between human and mouse, their emergence might have led to species-specific evolution. Our results indicate that the generation of processed pseudogenes was not wholly futile but instead has been an indispensable resource, driving dynamic evolution of the mammalian genomes. © 2006 Elsevier B.V. All rights reserved.
  • Takeshi Itoh, Tsuyoshi Tanaka, Roberto A. Barrero, Chisato Yamasaki, Yasuyuki Fujii, Phillip B. Hilton, Baltazar A. Antonio, Hideo Aono, Rolf Apweiler, Richard Bruskiewich, Thomas Bureau, Frances Burr, Antonio Costa De Oliveira, Galina Fuks, Takuya Habara, Georg Haberer, Bin Han, Erimi Harada, Aiko T. Hiraki, Hirohiko Hirochika, Douglas Hoen, Hiroki Hokari, Satomi Hosokawa, Yue Ie Hsing, Hiroshi Ikawa, Kazuho Ikeo, Tadashi Imanishi, Yukiyo Ito, Pankaj Jaiswal, Masako Kanno, Yoshihiro Kawahara, Toshiyuki Kawamura, Hiroaki Kawashima, Jitendra P. Khurana, Shoshi Kikuchi, Setsuko Komatsu, Kanako O. Koyanagi, Hiromi Kubooka, Damien Lieberherr, Yao Cheng Lin, David Lonsdale, Takashi Matsumoto, Akihiro Matsuya, W. Richard McCombie, Joachim Messing, Akio Miyao, Nicola Mulder, Yoshiaki Nagamura, Jongmin Nam, Nobukazu Namiki, Hisataka Numa, Shin Nurimoto, Claire O'Donovan, Hajime Ohyanagi, Toshihisa Okido, Satoshi OOta, Naoki Osato, Lance E. Palmer, Francis Quetier, Saurabh Raghuvanshi, Naomi Saichi, Hiroaki Sakai, Yasumichi Sakai, Katsumi Sakata, Tetsuya Sakurai, Fumihiko Sato, Yoshiharu Sato, Heiko Schoof, Motoaki Seki, Michie Shibata, Yuji Shimizu, Kazuo Shinozaki, Yuji Shinso, Nagendra K. Singh, Brian Smith-White, Jun Ichi Takeda, Motohiko Tanino, Tatiana Tatusova, Supat Thongjuea, Fusano Todokoro, Mika Tsugane, Akhilesh K. Tyagi, Apichart Vanavichit, Aihui Wang, Rod A. Wing, Kaori Yamaguchi, Mayu Yamamoto, Naoyuki Yamamoto, Yeisoo Yu, Hao Zhang, Qiang Zhao, Kenichi Higo, Benjamin Burr, Takashi Gojobori, Takuji Sasaki
    Genome Research 17 2 175 - 183 2007年02月 [査読有り][通常論文]
     
    We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is ∼32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene. ©2007 by Cold Spring Harbor Laboratory Press.
  • Jun Ichi Takeda, Yutaka Suzuki, Mitsuteru Nakao, Roberto A. Barrero, Kanako O. Koyanagi, Lihua Jin, Chie Motono, Hiroko Hata, Takao Isogai, Keiichi Nagai, Tetsuji Otsuki, Vladimir Kuryshev, Masafumi Shionyu, Kei Yura, Mitiko Go, Jean Thierry-Mieg, Danielle Thierry-Mieg, Stefan Wiemann, Nobuo Nomura, Sumio Sugano, Takashi Gojobori, Tadashi Iman ishi
    Nucleic Acids Research 34 14 3917 - 3928 2006年 [査読有り][通常論文]
     
    We report the first genome-wide identification and characterization of alternative splicing in human gene transcripts based on analysis of the full-length cDNAs. Applying both manual and computational analyses for 56 419 completely sequenced and precisely annotated full-length cDNAs selected for the H-Invitational human transcriptome annotation meetings, we identified 6877 alternative splicing genes with 18 297 different alternative splicing variants. A total of 37 670 exons were involved in these alternative splicing events. The encoded protein sequences were affected in 6005 of the 6877 genes. Notably, alternative splicing affected protein motifs in 3015 genes, subcellular localizations in 2982 genes and transmembrane domains in 1348 genes. We also identified interesting patterns of alternative splicing, in which two distinct genes seemed to be bridged, nested or having overlapping protein coding sequences (CDSs) of different reading frames (multiple CDS). In these cases, completely unrelated proteins are encoded by a single locus. Genome-wide annotations of alternative splicing, relying on full-length cDNAs, should lay firm groundwork for exploring in detail the diversification of protein function, which is mediated by the fast expanding universe of alternative splicing variants. © 2006 Oxford University Press.
  • Yasuyuki Fujii, Takeshi Itoh, Ryuichi Sakate, Kanako O. Koyanagi, Akihiro Matsuya, Takuya Habara, Kaori Yamaguchi, Yayoi Kaneko, Takashi Gojobori, Tadashi Imanishi
    Gene 364 1-2 45 - 52 2005年12月30日 [査読有り][通常論文]
     
    In order to assist the progression of comparative genomics, we have developed a new web-based tool, named G-compass, for browsing and analysis of genome alignments. G-compass utilizes 829,311 pieces of genome alignments between human and mouse that were originally produced for this tool. The quality of the genome alignment set was evaluated by using several statistics. As a result, the alignment set is found to cover approximately 17% of the human genome and 82% of the annotated exons. The averages of nucleotide sequence identity and sequence length are 71.2% and 673.6 bp, respectively. In comparison with public data, it appeared that our data is more expansive and possesses greater genome coverage. G-compass incorporates unique functions such as window analysis of individual alignments. Furthermore, with G-compass and the joint help of H-InvDB, we were able to find highly conserved genomic segments and a human specific antisense transcript candidate, demonstrating that G-compass is useful for facilitating biological discoveries. G-compass is publicly accessible on the WWW at http://www.jbirc.aist.go.jp/g-compass/. © 2005 Elsevier B.V. All rights reserved.
  • Chisato Yamasaki, Kanako O. Koyanagi, Yasuyuki Fujii, Takeshi Itoh, Roberto Barrero, Takuro Tamura, Yumi Yamaguchi-Kabata, Motohiko Tanino, Jun Ichi Takeda, Satoshi Fukuchi, Satoru Miyazaki, Nobuo Nomura, Sumio Sugano, Tadashi Imanishi, Takashi Gojobori
    Gene 364 1-2 99 - 107 2005年12月30日 [査読有り][通常論文]
     
    H-Invitational Database (H-InvDB; http://www.h-invitational.jp/) is a human transcriptome database, containing integrative annotation of 41,118 full-length cDNA clones originated from 21,037 loci. H-InvDB is a product of the H-Invitational project, an international collaboration to systematically and functionally validate human genes by analysis of a unique set of high quality full-length cDNA clones using automatic annotation and human curation under unified criteria. Here, 19,574 proteins encoded by these cDNAs were classified into 11,709 function-known and 7865 function-unknown hypothetical proteins by similarity with protein databases and motif prediction (InterProScan). The proportion of "hypothetical proteins" in H-InvDB was as high as 40.4%. In this study, we thus conducted data-mining in H-InvDB with the aim of assigning advanced functional annotations to those hypothetical proteins. First, by data-mining in the H-InvDB version of GTOP, we identified 337 SCOP domains within 7865 H-Inv hypothetical proteins. Second, by data-mining of predicted subcellular localization by SOSUI and TMHMM in H-InvDB, we found 1032 transmembrane proteins within H-Inv hypothetical proteins. These results clearly demonstrate that structural prediction is effective for functional annotation of proteins with unknown functions. All the data in H-InvDB are shown in two main views, the cDNA view and the Locus view, and five auxiliary databases with web-based viewers; DiseaseInfo Viewer, H-ANGEL, Clustering Viewer, G-integra and TOPO Viewer; the data also are provided as flat files and XML files. The data consists of descriptions of their gene structures, novel alternative splicing isoforms, functional RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite repeat motifs in relation with orphan diseases, gene expression profiling, and comparisons with mouse full-length cDNAs in the context of molecular evolution. This unique integrative platform for conducting in silico data-mining represents a substantial contribution to resources required for the exploration of human biology and pathology. © 2005 Elsevier B.V. All rights reserved.
  • Kanako O. Koyanagi, Masato Hagiwara, Takeshi Itoh, Takashi Gojobori, Tadashi Imanishi
    Gene 353 2 169 - 176 2005年07月04日 [査読有り][通常論文]
     
    Arrangement of genes in the human genome was not considered to be ordered like those of prokaryotes, as in many cases genes appeared to be randomly distributed across the genome. However, by focusing on the closely located adjacent gene pairs, it was recently suggested that the bidirectional pairs were enriched in the human genome and these pairs tended to be coexpressed by sharing promoter sequences. We compared this biased organization found in the human genome with those in the genomes of nine other eukaryotes to reveal when and how the biased organization had evolved using a total of 122,945 adjacent gene pairs. As a result, we found that the biased organization was found only in mammals, and not in other eukaryotes. Interestingly, we found that many of these genes in the bidirectional arrangement were not mammalian specific genes but conserved among various animals. Further analyses revealed that the bidirectional arrangement of these pairs had arisen by utilizing already-existing genes in the lineage leading to mammals recently, no earlier than the vertebrate-ascidian divergence. Since the novel bidirectional arrangement could result in novel co-regulated transcription, our results here provide evidence that shows how a transcriptional regulation system has evolved through changes in the genome organization, especially in the lineage leading to humans. © 2005 Elsevier B.V. All rights reserved.
  • Tadashi Imanishi, Takeshi Itoh, Yutaka Suzuki, Claire O'Donovan, Satoshi Fukuchi, Kanako O. Koyanagi, Roberto A. Barrero, Takuro Tamura, Yumi Yamaguchi-Kabata, Motohiko Tanino, Kei Yura, Satoru Miyazaki, Kazuho Ikeo, Keiichi Homma, Arek Kasprzyk, Tetsuo Nishikawa, Mika Hirakawa, Jean Thierry-Mieg, Danielle Thierry-Mieg, Jennifer Ashurst, Libin Jia, Mitsuteru Nakao, Michael A. Thomas, Nicola Mulder, Youla Karavidopoulou, Lihua Jin, Sangsoo Kim, Tomohiro Yasuda, Boris Lenhard, Eric Eveno, Yoshiyuki Suzuki, Chisato Yamasaki, Jun Ichi Takeda, Craig Gough, Phillip Hilton, Yasuyuki Fujii, Hiroaki Sakai, Susumu Tanaka, Clara Amid, Matthew Bellgard, Maria de Fatima Bonaldo, Hidemasa Bono, Susan K. Bromberg, Anthony J. Brookes, Elspeth Bruford, Piero Carninci, Claude Chelala, Christine Couillault, Sandro J. de Souza, Marie Anne Debily, Marie Dominique Devignes, Inna Dubchak, Toshinori Endo, Anne Estreicher, Eduardo Eyras, Kaoru Fukami-Kobayashi, Gopal R. Gopinath, Esther Graudens, Yoonsoo Hahn, Michael Han, Ze Guang Han, Kousuke Hanada, Hideki Hanaoka, Erimi Harada, Katsuyuki Hashimoto, Ursula Hinz, Momoki Hirai, Teruyoshi Hishiki, Ian Hopkinson, Sandrine Imbeaud, Hidetoshi Inoko, Alexander Kanapin, Yayoi Kaneko, Takeya Kasukawa, Janet Kelso, Paul Kersey, Reiko Kikuno, Kouichi Kimura, Bernhard Korn, Vladimir Kuryshev, Izabela Makalowska, Takashi Makino, Shuhei Mano, Regine Mariage-Samson, Jun Mashima, Hideo Matsuda, Hans Werner Mewes, Shinsei Minoshima, Keiichi Nagai, Hideki Nagasaki, Naoki Nagata, Rajni Nigam, Osamu Ogasawara, Osamu Ohara, Masafumi Ohtsubo, Norihiro Okada, Toshihisa Okido, Satoshi Oota, Motonori Ota, Toshio Ota
    PLoS Biology 2 6 e162  2004年 [査読有り][通常論文]
     
    The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
  • Kundu Srinesh, Hagiwara Masato, Koyanagi Kanako O., Imanishi Tadashi, Itoh Takeshi
    Genome Informatics 14 583 - 584 Japanese Society for Bioinformatics 2003年
  • Sakai Hiroaki, Koyanagi Kanako O., Itoh Takeshi, Imanishi Tadashi, Gojobori Takashi
    Genome Informatics 14 452 - 453 Japanese Society for Bioinformatics 2003年
  • Hayakawa Yousuke, Koyanagi Kanako, Tamura Takuro, Gojobori Takashi, Imanishi Tadashi
    Genome Informatics 12 466 - 468 Japanese Society for Bioinformatics 2001年
  • Kanako Ono-Koyanagi, Hiroshi Suga, Kazutaka Katoh, Takashi Miyata
    Journal of Molecular Evolution 50 3 302 - 311 2000年 [査読有り][通常論文]
     
    Since separation from fungi and plants, multicellular animals evolved a variety of gene families involved in cell-cell communication from a limited number of ancestral precursors by gene duplications in two separate periods of animal evolution. In the very early evolution of animals before the separation of parazoans and eumetazoans, animals underwent extensive gene duplications by which different subtypes (subfamilies) with distinct functions diverged. The multiplicity of members (isoforms) in the same subtype increased by further gene duplications (isoform duplications) in the first half of chordate evolution before the fish-tetrapod split; different isoforms are virtually identical in structure and function but differ in tissue distribution. From cloning and phylogenetic analyses of four subfamilies of the protein tyrosine kinase (PTK) family, we recently showed extensive isoform duplications in a limited period around or just before the cyclostome-gnathostome split. To obtain a reliable estimate for the divergence time of vertebrate isoforms, we have conducted isolation of cDNAs encoding the protein tyrosine phosphatases (PTPs) from Branchiostoma belcheri, an amphioxus, Eptatretus burgeri, a hagfish, and Potamotrygon motoro, a ray. We obtained 33 different cDNAs in total, most of which belong to known PTP subfamilies. The phylogenetic analyses of five subfamilies based on the maximum likelihood method revealed frequent isoform duplications in a period around or just before the gnathostome-cyclostome split. An evolutionary implication was discussed in relation to the Cambrian explosion.
  • H Suga, M Koyanagi, D Hoshiyama, K Ono, N Iwabe, K Kuma, T Miyata
    JOURNAL OF MOLECULAR EVOLUTION 48 6 646 - 653 1999年06月 [査読有り][通常論文]
     
    To know whether genes involved in cell-cell communication typical of multicellular animals dramatically increased in concert with the Cambrian explosion, the rapid evolutionary burst in the major groups of animals, and whether these genes exist in the sponge lacking cell cohesiveness and coordination typical of eumetazoans, we have carried out cloning of the Cr-protein a subunit (Ga) and the protein tyrosine kinase (PTK) cDNAs from Ephydatia fluviatilis (freshwater sponge) and Hydra magnipapillata strain 105 (hydra). We obtained 13 G alpha and 20 PTK cDNAs. Generally animal gene families diverged first by gene duplication (subtype duplication) that Save rise to diverse subtypes with different primary functions, followed by further gene duplication in the same subtype (isoform duplication) that gave rise to isoform genes with virtually identical function. Phylogenetic trees of Ga and PTK families including cDNAs from sponge and hydra revealed that most of the present-day subtypes had been established in the very early evolution of animals before the parazoaneumetazoan split, the earliest branching among the extant animal phyla, by extensive subtype duplication: for PTK and Ga families, 23 and 9 subtype duplications were observed in the early stage before the parazoaneumctazoan split, respectively, and after that split, only 2 and 1 subtype duplications were found, respectively. After the separation from arthropods, vertebrates underwent frequent isoform duplications before the fish-tetrapod split. Furthermore, rapid amino acid changes appear to have occurred in concert with the extensive subtype duplication and isoform duplication. Thus the pattern of gene diversification during animal evolution might be characterized by bursts of gene duplication interrupted by considerably long periods of silence, instead of proceeding gradually, and there might be no direct link between the Cambrian explosion and the extensive gene duplication that generated diverse functions (subtypes) of these families.
  • K Ono, H Suga, N Iwabe, K Kuma, T Miyata
    JOURNAL OF MOLECULAR EVOLUTION 48 6 654 - 662 1999年06月 [査読有り][通常論文]
     
    Protein tyrosine phosphatases (PTPs) regulate various physiological events in animal cells. They comprise a diverse family which are classified into two categories, receptor type and nonreceptor type. From the domain organization and phylogenetic tree, we have classified known PTPs: into 17 subtypes (9 receptor-type and 8 nonreceptor-type PTPs) which are characterized by different organization of functional domain and independent cluster in tree. The receptor type PTPs are thought to be implicated in cell-cell adhesion by association of cell adhesion molecules. Since sponges are the most primitive multicellular animals and are thought to be lacking cell cohesiveness and coordination typical of eumetazoans, cloning and sequencing of PTP cDNAs of Ephydatia fluviatilis (freshwater sponge) have been conducted by RT-PCR to determine whether or not sponges have PTP genes in their genomes. We have isolated nine PTPs, of which five are possibly receptor type. A phylogenetic tree including the sponge PTPs revealed that most of the gene duplications that gave rise to the 17 subtypes had been completed in the very early evolution of animals before the parazoan-eumetazoan split, the earliest branching among extant animal phyla, The family tree also revealed the rapid evolutionary rate of PTP subtypes in the early stage of animal evolution.
  • H Suga, O Kanako, T Miyata
    FEBS LETTERS 453 3 346 - 350 1999年06月 [査読有り][通常論文]
     
    Members of the transforming growth factor beta (TGF-beta) family mediate key events in cell growth and development. Various receptors for diverse members of the TGF-beta family have recently been isolated and sequenced. These receptors form a family (T beta R family),vith a Ser/Thr kinase domain in common. To understand the divergence pattern of the T beta R family during animal evolution, we hale conducted cloning of cDNAs encoding the T beta R family members from Ephydatia fluviatilis, a freshwater sponge. We obtained seven cDNAs (sALK-1-sALK-7) which are closely related in structure to known family members. Including these sponge sequences, a phylogenetic tree of the family members nas inferred by a maximum likelihood method. The phylogenetic tree suggests that the sponge receptors sALK-1-sALK-3, which are closely related to each other, are sponge homologs of vertebrate activin type I receptor (ActR-I), sALK-5 is likely to be a homolog of TGF-beta type II receptor. sALK-4 and sALK-6 might be ancestral precursors of type I and type II receptors, respectively, and sALK-7 is possibly an ancestral precursor of both types, The tree revealed that most, if not all, of the gene duplications that gave rise to known subtypes with distinct ligand specificities antedate the divergence of parazoans and eumetazoans, the earliest divergence of extant animal phyla. (C) 1999 Federation of European Biochemical Societies.
  • M Koyanagi, K Ono, H Suga, N Iwabe, T Miyata
    FEBS LETTERS 439 1-2 66 - 70 1998年11月 [査読有り][通常論文]
     
    To know whether or not the set of genes involved in the inositol phospholipid signaling pathway already existed in the early evolution of animals, me carried out cloning of cDNAs encoding phospholipase Cs (PLCs) from Ephydatia fluviatilis (freshwater sponge) and Hydra magnipapillata strain 105 (hydra), We isolated two PLC cDNAs, PLC-PS and PLC-gamma S, from sponge and three cDNAs, PLC-beta H1, PLC-beta H2, and PLC-delta H, from hydra, From the domain organization and the divergence pattern in the PLC family tree, the sponge PLC-PS and PLC-gamma S and the hydra PLC-GH are possibly homologous to the vertebrate PLC-beta, PLC-gamma and PLC-delta subtypes, respectively. A detailed phylogenetic analysis suggests that the hydra PLC-beta H1 and PLC-beta H2 are homologs of the vertebrate PLC-beta 1/2/3/ Drosophila PLC21 and the vertebrate PLC-beta 4/Drosophila norpA, respectively. A phylogenetic analysis of the PLC family and the protein kinase C (PKC) family, together with that of the C protein alpha subunit (G alpha) family, revealed that the origin of the set of genes G alpha q, PLC, PKC involved in the inositol phospholipid signaling pathway is very old, going back to dates before the parazoan-eumetazoan split, the earliest branching among extant animal phyla, (C) 1998 Federation of European Biochemical Societies.
  • M Koyanagi, H Suga, D Hoshiyama, K Ono, N Iwabe, K Kuma, T Miyata
    FEBS LETTERS 436 3 323 - 328 1998年10月 [査読有り][通常論文]
     
    The animal cyclic nucleotide phosphodiesterases (PDEs) comprise at least seven subtypes, PDE1-7, which differ from each other in domain organization and primary function, and they diverged from an ancestral gene by gene duplication and domain shuffling during animal evolution. To obtain rough estimates for the divergence times of these subtypes, cloning of PDE cDNAs from Ephydatia fluviatilis (freshwater sponge) by RT-PCR was carried out. We obtained four cDNAs, EFPDE1, EFPDE2, EFPDE3, and EFPDE4, which are possibly homologs of the vertebrate PDE1, PDE2, PDE3, and PDE4, respectively, judging from the sequence similarity, domain organization, and branching pattern in the phylogenetic tree. The phylogenetic tree of the PDE family revealed that most gene duplications and domain shufflings that gave rise to different subtypes had been completed in the early evolution of animals before the separation of sponges and eumetazoans, (C) 1998 Federation of European Biochemical Societies.
  • Daisuke Hoshiyama, Hiroshi Suga, Naoyuki Iwabe, Mitsumasa Koyanagi, Naruo Nikoh, Kei-Ichi Kuma, Fumihiko Matsuda, Tasuku Honjo, Takashi Miyata
    Journal of Molecular Evolution 47 6 640 - 648 1998年 [査読有り][通常論文]
     
    Members of the Pax gene family encode transcription factors containing a DNA-binding paired domain which is involved in developmental control and the formation of the central nervous system (CNS). The family members are classified into six classes or subfamilies, depending on the presence or absence of paired-type homeobox and octapeptide. To obtain rough estimates of times when the different classes of the Pax family diverged by gene duplication, we cloned and sequenced a Pax-related cDNA, sPax-2/5/8, from Ephydatia fluviatilis, a freshwater sponge, which encodes a paired-type homeobox and an octapeptide, in addition to a paired domain. A phylogenetic tree based on the paired domain sequences suggest that sPax-2/5/8 is a homologue of vertebrate Pax-2/5/8. It was also suggested that the majority of gene duplications that gave rise to distinct classes has been completed in the very early evolution of animals before the parazoan-eumetazoan split. Long after the ancient gene duplications, further gene duplications that gave rise to members in each subfamily occurred on the chordate lineages and completed before the fish-tetrapod split. This suggests that the major classes of the Pax genes involved in the formation of CNS characteristic of triploblasts had already existed long before the Cambrian explosion of triploblasts, and there is no direct link between the creation of new genes with novel functions and the Cambrian explosion. The pattern of gene diversification found in the Pax family is similar to those in five gene families involved in the signal transduction analyzed by us. Furthermore, the evolutionary rates of the Pax proteins have been shown to decrease with increasing organismal complexity during animal evolution.
  • H Suga, K Kuma, N Iwabe, N Nikoh, K Ono, M Koyanagi, D Hoshiyama, T Miyata
    FEBS LETTERS 412 3 540 - 546 1997年08月 [査読有り][通常論文]
     
    The protein tyrosine kinases (PTKs) are a large protein family consisting of many subfamilies with a variety of domain structures, The basic functions are thought to differ for different subfamilies. To know the dates at which the subfamilies diverged by gene duplications, a phylogenetic tree of the PTKs was inferred by comparing sequences from a nide range of species covering diploblasts and triploblasts. The PTK tree revealed that almost all of the gene duplications that gave rise to different subfamilies occurred rapidly before the diploblast-triploblast split, accompanying with rapid amino acid substitutions, This type of gene duplication was, however, rarely observed after that split, Long after the subfamily divergence, another type of gene duplication that gave rise to diverse tissue-specific genes occurred in each subfamily on the chordate lineage since the separation from arthropods, This type of gene duplication occurred frequently before the fish-tetrapod split, accompanying with rapid amino acid substitutions, In contrast, both the frequency of gene duplications and the rate of the amino acid substitutions were considerably reduced after that split, These results strongly suggest that the PTKs diverged intermittently, but not gradually, during animal evolution. (C) 1997 Federation of European Biochemical Societies.

書籍

  • ニコラス・H. バートン, ジョナサン・A. アイゼン, デイビッド・B, ゴールドステイン, ニパム・H. パテル, デレク・E.G. ブリッグス 
    メディカルサイエンスインターナショナル 2009年12月 (ISBN: 4895926214) 908

講演・口頭発表等

  • 比較ゲノム解析によるO. sativa ssp. japonicaとイネ属AAゲノム種のイントログレッション領域の探索  [通常講演]
    小柳 香奈子, 神徳 雄太, 貴島 祐治
    日本育種学会第145回講演会 2024年03月 口頭発表（一般）
  • オミクス情報の系統解析による細胞分化過程推定の可能性  [招待講演]
    小柳香奈子
    第46回日本分子生物学会年会 フォーラム1F-15「ゲノム起源を討論する学問所」 2023年12月 神戸市
  • オープンクロマチン情報の系統解析による細胞分化過程の推定  [通常講演]
    小柳香奈子
    日本遺伝学会第95回大会 2023年09月 口頭発表（一般）
  • エピゲノム情報の系統解析による細胞分化過程の推定  [招待講演]
    小柳香奈子
    遺伝研研究集会「生命科学を支える分子系統学」 2022年08月
  • Inferring cell differentiation processes based on phylogenetic analysis of epigenomes  [招待講演]
    Kanako O. Koyanagi
    The 24th Hokkaido University – Seoul National University Joint Symposium 2021年11月 口頭発表（招待・特別）
  • Inferring cell type tree based on phylogenetic analysis of genome-wide epigenetic information  [通常講演]
    Kanako O. Koyanagi
    EMBO | EMBL Symposium: The Identity and Evolution of Cell Types 2021年05月 ポスター発表
  • Inferring cell differentiation processes based on phylogenetic analysis of genome-wide epigenetic information  [通常講演]
    Kanako O. Koyanagi
    SMBE 2018 2018年07月 ポスター発表
  • エピゲノム情報の系統解析による細胞分化過程の推定 —哺乳類の血球系細胞分化をモデルとして  [招待講演]
    小柳香奈子
    分子生物学会 2017年12月 シンポジウム・ワークショップパネル（指名）
  • Inferring cell differentiation processes based on phylogenetic analysis of genome-wide epigenetic information  [通常講演]
    Kanako O. Koyanagi
    CDB symposium 2017 2017年03月 ポスター発表
  • Inferring cell differentiation processes based on phylogenetic analysis of genome-wide epigenetic information  [通常講演]
    Kanako O. Koyanagi
    THE 40th NAITO CONFERENCE on Epigenetics―From Histone Code to Therapeutic Strategy 2015年09月 ポスター発表
  • 新規遺伝子同定法 FATES;その特徴と今後の展開 「基盤整備~専用解析プログ ラムFATESerの開発」  [通常講演]
    小柳香奈子
    日本育種学会 第128回講演会・新潟 2015年09月 シンポジウム・ワークショップパネル（公募）
  • ヒストン修飾情報の系統解析による細胞分化過程の推定 ーヒト血球系細胞をモデルとして  [通常講演]
    小柳香奈子
    日本進化学会 第17回大会・東京 2015年08月
  • Inferring cell differentiation processes based on the phylogenetic analysis of genome-wide DNA methylation data: Hematopoiesis as a model case  [通常講演]
    Kanako O. Koyanagi
    Keystone Symposia Conference (Z1: DNA Methylation) 2015年03月 ポスター発表
  • アデノウイルスのゲノム進化を可能にする組換えと置換の特徴  [招待講演]
    小柳香奈子
    第15回アデノウィルス研究会 品川インターシティ 2014年11月
  • エピジェネティック情報の最尤推定による細胞分化過程の推定 ーマウス血球系細胞をモデルとして  [通常講演]
    小柳香奈子
    日本進化学会 第16回大会・高槻 2014年08月 ポスター発表
  • エピジェネティック情報の系統解析による細胞分化過程の推定 ーマウス血球系細胞をモデルとして  [通常講演]
    小柳香奈子
    日本分子生物学会 第36回・神戸 2013年12月 ポスター発表
  • エピジェネティック情報の系統解析による細胞分化過程の推定 ーマウス血球系細胞をモデルとして  [通常講演]
    小柳香奈子
    日本進化学会 第15回大会・つくば 2013年08月 口頭発表（一般）

その他活動・業績

受賞

  • 2021年 公益財団法人 秋山記念生命科学振興財団 研究助成〈一般〉
     リアルタイム選別による未知DNA配列解読－北海道イネゲノム難解読領域への応用－ 
    受賞者: 小柳香奈子;渡邉日出海
  • 2005年 日本遺伝学会 第７７回日本遺伝学会BP賞
     脊椎動物特異的なゲノム構造進化の発見 
    受賞者: 小柳香奈子;伊藤剛;萩原正人;五條堀孝;今西規

共同研究・競争的資金等の研究課題

  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2022年04月 -2025年03月 
    代表者 : 小柳 香奈子
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2016年04月 -2020年03月 
    代表者 : 小柳 香奈子
     
    多細胞動物の発生過程の理解には、各細胞の変遷過程の理解が重要である。しかしながら侵襲的な実験が難しいヒトなど、変遷過程の全種類の細胞を網羅的に取得することは困難な場合も多い。そこで本研究では、得ることが比較的容易な成体の分化した体細胞のエピジェネティック修飾の情報を用い、進化学で用いられる系統解析から、細胞分化過程におけるエピジェネティック修飾の変遷過程の推定を試みた。材料として8種類のヒト血球系細胞の6種類のヒストン修飾を用い、本手法により、細胞分化に関連したヒストン修飾の変遷過程が推定されうることが示唆された。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2013年04月 -2017年03月 
    代表者 : 小柳 香奈子
     
    受精卵が遺伝子の発現状態を変化させながら、細胞分裂・分化・移動・死を通して、どのようにして多種類の細胞からなる一個体が形成されるのかを理解することは、生物学の大きな目標の一つである。本研究では、体細胞エピゲノム情報の系統解析からin silicoで細胞系譜を構築し、さらに細胞系譜の祖先節の形質状態、すなわち発生過程の細胞のエピゲノム状態を推定することで、この問題の解決を試みた。その結果、マウス血球系細胞のゲノムワイドなDNAメチル化情報の系統解析により、既知の細胞系譜や分化途中の細胞のDNAメチル化状態の推定が可能なことが示された。さらにヒト成体の各種細胞への応用を試みた。
  • 日本学術振興会：科学研究費助成事業 挑戦的萌芽研究
    研究期間 : 2014年04月 -2016年03月 
    代表者 : 松島 綾美, 小柳 香奈子
     
    エンドモルフィンは、アミノ酸４つからなる神経ペプチドである。モルヒネを凌ぐ強力な鎮痛作用があり、痒みとの関連も非常に注目されている。しかし、未だにエンドモルフィン遺伝子は不明のままなのである。近年では、ゲノムから短いペプチドを見出す難しさが認識され、ペプチドを網羅的に質量分析するペプチドーム解析にも注目が集まりつつある。こうしたなか、次世代シークエンサーを用いた網羅的解析とRNA編集を考慮した情報処理技術の両面からの探索を試みた。結果としてエンドモルフィン遺伝子単離には至らなかった。しかし、エンドモルフィン様ペプチド遺伝子を見出し、これに基づいた合成ペプチドはオピオイド受容体と弱く結合した。
  • 地域の育種集団におけるFNPsハプロタイプを用いた高速ゲノム育種法の開発
    農林水産省：農林水産業・食品産業科学技術研究推進事業 シーズ創出ステージ
    研究期間 : 2013年 -2016年03月 
    代表者 : 藤野 賢治
  • 日本学術振興会：科学研究費助成事業 新学術領域研究(研究領域提案型)
    研究期間 : 2010年04月 -2015年03月 
    代表者 : 渡邉 日出海, 小柳 香奈子
     
    真核細胞内で生じる組換えの特性を明らかにすることを目的として、ヒトアデノウイルス(HAdV)のゲノム配列決定と比較解析を進めている。平成23年度においては、これまでに札幌において定点採集された流行性角結膜炎(EKC)発症性HAdVVの計10ゲノムをテロメア領域を含めて完全に配列決定した。また、米国、シンガポール、ハンガリーから、日本において見られなくなったHAdV-8のゲノムDNAを収集し、配列決定を進めている。これらのHAdVゲノム配列を他の既知ゲノム配列を含めて比較解析し、組換え頻度を調べたところ、これまでの血清型等の解析から示唆されていたウイルス表面たんぱく質遺伝子において実際に点突然変異率に比して有意な組換え境界頻度が検出された。興味深いことに、それ以上の頻度で、E3領域に存在する、ウイルスのホスト細胞への侵入過程で用いられる遺伝子や機能未知遺伝子においてきわめて高い組換え頻度が検出された。これら組換えホットスポットにおける組換えが、ゲノム全体で一様に起きる組換えのうちで自然選択の結果残ったものであるのか、あるいは、これらの遺伝子内に組換えを誘起する領域が存在するのかを明らかにするための解析を行った結果、組換えホットスポット近傍に遠縁ウイルス間で高度の保存している領域を見出すことが出来、後者の可能性が示唆された。真核生物ゲノムにおける挿入欠失の発生特性を明らかにするた...
  • エピゲノミクスとファイロゲノミクスの融合による哺乳類細胞系譜再構築の試み
    北海道大学大学院情報科学研究科：大学院情報科学研究科若手研究費
    研究期間 : 2012年07月 -2013年03月 
    代表者 : 小柳香奈子
  • 日本学術振興会：科学研究費助成事業 基盤研究(B)
    研究期間 : 2010年 -2012年 
    代表者 : 貴島 祐治, 小柳 香奈子, 安井 秀
     
    ネゲノムに見いだされる内在性RTBVウイルス配列(ERTBV配列)を日本型日本晴系統やインド型93-11系統で特定し、それらの挿入機構やツングロ病との耐性機構について解析した。ERTBVはゲノムの中のATが連続している領域に挿入する傾向が高く、AT連続配列は外来からDNA断片を取り込む可能性が強く示唆された。また、アフリカイネ系統のWK18と日本型台中65の交雑後代で、イネ染色体5番にRTBV抵抗性を示す遺伝子領域qTDR5を見いだした。qTDR5の中にはERTBVが1箇所含まれている。
  • 日本学術振興会：科学研究費助成事業 若手研究(B)
    研究期間 : 2006年 -2008年 
    代表者 : 小柳 香奈子
     
    本研究の目的は、ヒトゲノム情報解析から染色体間の相互作用を示す情報を抽出し、核内における染色体の核内配置との関連性を検証することである。本研究では、染色体間の相互作用を示す情報として、ヒトゲノム中にみられるプロセス型偽遺伝子とゲノム内重複領域の染色体分布を解析し、染色体間の偏りを検出した。またこの研究の過程において、種特異的な重複領域を高精度に同定する目的で、分子進化解析に基づくゲノム直系領域の同定方法を開発した。
  • 日本学術振興会：科学研究費助成事業 特定領域研究
    研究期間 : 2006年 -2007年 
    代表者 : 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...
  • 日本学術振興会：科学研究費助成事業 若手研究(B)
    研究期間 : 2004年 -2005年 
    代表者 : 小柳 香奈子
     
    申請者のこれまでの研究から、ヒトゲノム上の遺伝子位置及びその構造に偏りがあることが明らかとなっていた。そこで、本課題ではこの偏りの意義の解明すること(目的1)、さらにこの遺伝子構造の進化過程を明らかにすること(目的2)、を目的として研究を行った。まず、ヒトゲノム上で偏りのみられたhead-to-head遺伝子ペアについて、成人における組織特異性に関する発現情報を用いて、遺伝子ペア間の発現パターンの比較を行った。その結果、遺伝子ペア間では弱いながら発現組織に相関がみられることがわかった。また、遺伝子ペア間において何か共通の特徴はないか、機能アノテーション情報を比較したが、機能アノテーションには特徴的な偏りはみられないことがわかった。これらのことから、ヒトゲノム構造にみられる偏りと遺伝子発現調節との間に関連性のあることが示唆された。次に、ヒトゲノム上でみられたゲノム構造の偏りが他の生物種でも保存しているか、それはヒトに至る進化の過程でいつ頃進化したのか、また他の生物種にその生物種固有のヒトとは異なった偏りや特徴がないか、といった点について解明する目的で、ヒト以外の生物種(マウス、フグ、ホヤ、ハエ、カ、線虫)についてゲノム構造の比較解析を行った。その結果、この遺伝子構造は哺乳類に特異的にみられるものであり、その他の真核生物にはみられない新しく進化した構造であること、という結果を得た...
  • 日本学術振興会：科学研究費助成事業 特定領域研究
    研究期間 : 2004年 -2004年 
    代表者 : 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...

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  • 2021年04月 - 2023年03月   文部科学省 科学技術・学術政策研究所 (NISTEP)   専門調査員
  • 2021年 - 2022年   日本遺伝学会第94回大会実行委員
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  • 北海道札幌東高等学校模擬授業
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    期間 : 2015年10月10日
    役割 : 講師
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    期間 : 2014年07月31日
    役割 : 講師
  • 日本植物学会 第4回男女共同参画セミナー
    期間 : 2013年09月13日
    役割 : パネリスト
  • 日本遺伝学会 男女共同参画ランチョンワークショップ
    期間 : 2010年09月21日
    役割 : パネリスト
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    期間 : 2009年10月03日
    役割 : 出演

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