研究者データベース

長田 直樹(オサダ ナオキ)
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

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)(東京大学)

論文上での記載著者名

  • Naoki Osada

ホームページURL

科研費研究者番号

  • 70416270

J-Global ID

プロフィール

  • 分子生物学実験,集団遺伝学,バイオインフォマティクスなどの方法を用いて進化の問題に答えようと思っています.ヒトを含めた霊長類を中心に,ショウジョウバエや植物のデータも扱っています.興味がわけば何でもやります.

研究キーワード

  • 遺伝子重複   遺伝子発現調節   再編   カニクイザル   CXCL1L   ケモカイン   偽遺伝子   ゲノム進化   翻訳   CXCL1   グノム   種分化   生態学   霊長類   進化   遺伝学   遺伝子交流   

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 / ゲノム生物学
  • ライフサイエンス / 多様性生物学、分類学
  • ライフサイエンス / 進化生物学

職歴

  • 2019年04月 - 現在 北海道大学 大学院情報科学研究院 准教授
  • 2017年09月 - 現在 北海道大学 国際連携研究教育局 准教授
  • 2012年05月 - 現在 放射線医科学総合研究所 客員研究員
  • 2015年04月 - 2019年03月 北海道大学 大学院情報科学研究科 准教授
  • 2010年01月 - 2015年03月 国立遺伝学研究所・総合研究大学院大学 助教
  • 2011年12月 - 2011年12月 台湾国立成功大学 客員助理教授
  • 2009年01月 - 2009年12月 台湾国立成功大学 兼任助理教授
  • 2005年04月 - 2009年12月 独立行政法人医薬基盤研究所 研究員
  • 2004年10月 - 2005年03月 国立感染症研究所 研究官
  • 2003年03月 - 2004年10月 シカゴ大学 リサーチアソシエイト
  • 2002年04月 - 2002年12月 東京大学 特別研究員

学歴

  • 1997年04月 - 2002年03月   東京大学大学院   理学系研究科   生物科学専攻
  • 1993年04月 - 1997年03月   東京大学   理学部   生物学科

所属学協会

  • 生き物文化誌学会   日本バイオインフォマティクス学会   日本人類学会   日本分子生物学会   日本霊長類学会   日本進化学会   日本遺伝学会   

研究活動情報

論文

  • Kyoko Saito, Masayoshi Fukasawa, Yoshitaka Shirasago, Ryosuke Suzuki, Naoki Osada, Toshiyuki Yamaji, Takaji Wakita, Eiji Konishi, Kentaro Hanada
    PloS one 15 4 e0232274  2020年 [査読有り][通常論文]
     
    The Flaviviridae is a family of enveloped viruses with a positive-sense single-stranded RNA genome. It contains many viruses that threaten human health, such as Japanese encephalitis virus (JEV) and yellow fever virus (YFV) of the genus Flavivirus as well as hepatitis C virus of the genus Hepacivirus. Cell culture systems highly permissive for the Flaviviridae viruses are very useful for their isolation, propagation, and diagnosis, an understanding of their biology, and the development of vaccines and antiviral agents. Previously, we isolated a human hepatoma HuH-7-derived cell clone, Huh7.5.1-8, which is highly permissive to hepatitis C virus infection. Here, we have characterized flavivirus infection in the Huh7.5.1-8 cell line by comparing with that in the African green monkey kidney-derived Vero cell line, which is permissive for a wide spectrum of viruses. Upon infection with JEV, Huh7.5.1-8 cells produced a higher amount of virus particles early in infection and were more susceptible to virus-induced cell death than Vero cells. Similar outcomes were obtained when the cells were infected with another flavivirus, YFV (17D-204 strain). Quantification of cellular and extracellular viral RNA revealed that high JEV production in Huh7.5.1-8 cells can be attributed to rapid viral replication kinetics and efficient virus release early in infection. In a plaque assay, Huh7.5.1-8 cells developed JEV plaques more rapidly than Vero cells. Although this was not the case with YFV plaques, Huh7.5.1-8 cells developed higher numbers of YFV plaques than Vero cells. Sequence analysis of cDNA encoding an antiviral RNA helicase, RIG-I, showed that Huh7.5.1-8 cells expressed not only a full-length RIG-I mRNA with a known dominant-negative missense mutation but also variants without the mutation. However, the latter mRNAs lacked exon 5/6-12, indicating functional loss of RIG-I in the cells. These characteristics of the Huh7.5.1-8 cell line are helpful for flavivirus detection, titration, and propagation.
  • Toshihide Higashino, Keito Morimoto, Hirofumi Nakaoka, Yu Toyoda, Yusuke Kawamura, Seiko Shimizu, Takahiro Nakamura, Kazuyoshi Hosomichi, Akiyoshi Nakayama, Keiko Ooyama, Hiroshi Ooyama, Toru Shimizu, Miki Ueno, Toshimitsu Ito, Takashi Tamura, Mariko Naito, Hiroshi Nakashima, Makoto Kawaguchi, Mikiya Takao, Yosuke Kawai, Naoki Osada, Kimiyoshi Ichida, Ken Yamamoto, Hiroshi Suzuki, Nariyoshi Shinomiya, Ituro Inoue, Tappei Takada, Hirotaka Matsuo
    Annals of the rheumatic diseases 79 1 164 - 166 2020年01月 [査読有り][通常論文]
  • Kazuhiro Satomura, Naoki Osada, Toshinori Endo
    Ecological Genetics and Genomics 13 100045  2019年09月 [査読有り][通常論文]
  • Yukiko Nakamura, Junya Yamagishi, Kyoko Hayashida, Naoki Osada, Elisha Chatanga, Cornelius Mweempwa, Kalinga Chilongo, John Chisi, Jenelisa Musaya, Ryosuke Omori, Noboru Inoue, Boniface Namangala, Chihiro Sugimoto
    PLoS Negl. Trop. Dis. 13 7 e0007568  2019年07月 [査読有り][通常論文]
  • Asano Ishikawa, Naoki Kabeya, Koki Ikeya, Ryo Kakioka, Jennifer N. Cech, Naoki Osada, Miguel C. Leal, Jun Inoue, Manabu Kume, Atsushi Toyoda, Ayumi Tezuka, Atsushi J. Nagano, Yo Y. Yamasaki, Yuto Suzuki, Tomoyuki Kokita, Hiroshi Takahashi, Kay Lucek, David Marques, Yusuke Takehana, Kiyoshi Naruse, Seiichi Mori, Oscar Monroig, Nemiah Ladd, Carsten J. Schubert, Blake Matthews, Catherine L. Peichel, Ole Seehausen, Goro Yoshizaki, Jun Kitano
    Science 364 886 - 889 2019年05月 [査読有り][通常論文]
  • Masaki Ikeda, Kazuhiro Satomura, Tsuyoshi Sekizuka, Kentaro Hanada, Toshinori Endo, Naoki Osada
    American Journal of Primatology e22882  2018年06月 [査読有り][通常論文]
  • Fan, Zhenxin, Anbo Zhou, Naoki Osada, Jianqiu Yu, Juan Jiang, Peng Li, Lianming Du, Lili Niu, Jiabo Deng, Huailiang Xu, Jinchuan Xing, Bisong Yue, Jing Li
    Molecular Phylogenetics and Evolution 127 376 - 387 2018年 [査読有り][通常論文]
  • Chisato Sakuma, Tsuyoshi Sekizuka, Makoto Kuroda, Fumio Kasai, Kyoko Saito, Masaki Ikeda, Toshiyuki Yamaji, Naoki Osada, Kentaro Hanada
    Scientific Reports 8 644  2018年01月 [査読有り][通常論文]
  • Yasuhiro Uno, Naoki Osada, Soichi Sakurai, Nobuhiro Shimozawa, Takeshi Iwata, Kazuho, Ikeo, Hiroshi Yamazaki
    Journal of Veterinary Pharmacology and Therapeutics 41 e30 - e34 2018年01月 [査読有り][通常論文]
  • Naoki Osada, Ryutaro Miyagi, Aya Takahashi
    GENETICS 206 4 2139 - 2148 2017年08月 [査読有り][通常論文]
     
    Cis- and trans-regulatory mutations are important contributors to transcriptome evolution. Quantifying their relative contributions to intraspecific variation in gene expression is essential for understanding the population genetic processes that underlie evolutionary changes in gene expression. Here, we have examined this issue by quantifying genome-wide, allele-specific expression (ASE) variation using a crossing scheme that produces F-1 hybrids between 18 different Drosophila melanogaster strains sampled from the Drosophila Genetic Reference Panel and a reference strain from another population. Head and body samples from F1 adult females were subjected to RNA sequencing and the subsequent ASE quantification. Cis- and trans-regulatory effects on expression variation were estimated from these data. A higher proportion of genes showed significant cis-regulatory variation (similar to 28%) than those that showed significant trans-regulatory variation (similar to 9%). The sizes of cis-regulatory effects on expression variation were 1.98 and 1.88 times larger than trans-regulatory effects in heads and bodies, respectively. A generalized linear model analysis revealed that both cis- and trans-regulated expression variation was strongly associated with nonsynonymous nucleotide diversity and tissue specificity. Interestingly, trans-regulated variation showed a negative correlation with local recombination rate. Also, our analysis on proximal transposable element (TE) insertions suggested that they affect transcription levels of ovary-expressed genes more pronouncedly than genes not expressed in the ovary, possibly due to defense mechanisms against TE mobility in the germline. Collectively, our detailed quantification of ASE variations from a natural population has revealed a number of new relationships between genomic factors and the effects of cis- and trans-regulatory factors on expression variation.
  • Yasuaki Takada, Ryutaro Miyagi, Aya Takahashi, Toshinori Endo, Naoki Osada
    G3-GENES GENOMES GENETICS 7 7 2227 - 2234 2017年07月 [査読有り][通常論文]
     
    Joint quantification of genetic and epigenetic effects on gene expression is important for understanding the establishment of complex gene regulation systems in living organisms. In particular, genomic imprinting and maternal effects play important roles in the developmental process of mammals and flowering plants. However, the influence of these effects on gene expression are difficult to quantify because they act simultaneously with cis-regulatory mutations. Here we propose a simple method to decompose cis-regulatory (i.e., allelic genotype), genomic imprinting [i.e., parent-of-origin (PO)], and maternal [i.e., maternal genotype (MG)] effects on allele-specific gene expression using RNA-seq data obtained from reciprocal crosses. We evaluated the efficiency of method using a simulated dataset and applied the method to whole-body Drosophila and mouse trophoblast stem cell (TSC) and liver RNA-seq data. Consistent with previous studies, we found little evidence of PO and MG effects in adult Drosophila samples. In contrast, we identified dozens and hundreds of mouse genes with significant PO and MG effects, respectively. Interestingly, a similar number of genes with significant PO effect were detect in mouse TSCs and livers, whereas more genes with significant MG effect were observed in livers. Further application of this method will clarify how these three effects influence gene expression levels in different tissues and developmental stages, and provide novel insight into the evolution of gene expression regulation.
  • Hisayuki Nomiyama, Naoki Osada, Ichiro Takahashi, Keiji Terao, Kazuya Yamagata, Osamu Yoshie
    JOURNAL OF INTERFERON AND CYTOKINE RESEARCH 37 3 129 - 138 2017年03月 [査読有り][通常論文]
     
    We previously isolated a cDNA clone from cynomolgus macaque encoding a novel CXC chemokine that we termed CXCL1L from its close similarity to CXCL1. However, the cDNA consisted of 3 exons instead of 4 exons that were typically seen in other CXC chemokines. Here, we isolated a cDNA encoding the full-length variant of CXCL1L that we termed CXCL1L beta. CXCL1L beta is 50 amino acids longer than the original CXCL1L, which we now term CXCL1L alpha. The CXCL1L beta mRNA is much more abundantly expressed in the cynomolgus macaque tissues than CXCL1L alpha mRNA. However, CXCL1L beta protein was poorly produced by transfected cells compared with that of CXCL1L alpha. When the coding region of the fourth exon was fused to the C-terminus of CXCL1 or even to a nonsecretory protein firefly luciferase, the fused proteins were also barely produced, although the mRNAs were abundantly expressed. The polysome profiling analysis suggested that the inhibition was mainly at the translational level. Furthermore, we demonstrated that the C-terminal 5 amino acids of CXCL1L beta were critical for the translational repression. The present study, thus, reveals a unique translational regulation controlling the production of a splicing variant of CXCL1L. Since the CXCL1L gene is functional only in the Old World monkeys, we also discuss possible reasons for the conservation of the active CXCL1L gene in these monkeys during the primate evolution.
  • Naoki Osada
    Encyclopedia of Evolutionary Biology 1 329 - 333 2016年05月 [査読有り][招待有り]
  • Tomotaka Matsumoto, Katsuhiko Mineta, Naoki Osada, Hitoshi Araki
    FRONTIERS IN GENETICS 6 336  2015年11月 [査読有り][通常論文]
     
    Recent studies suggest the existence of a stochasticity in gene expression (SGE) in many organisms, and its non-negligible effect on their phenotype and fitness. To date, however, how SGE affects the key parameters of population genetics are not well understood. SGE can increase the phenotypic variation and act as a load for individuals, if they are at the adaptive optimum in a stable environment. On the other hand, part of the phenotypic variation caused by SGE might become advantageous if individuals at the adaptive optimum become genetically less adaptive, for example due to an environmental change. Furthermore, SGE of unimportant genes might have little or no fitness consequences. Thus, SGE can be advantageous, disadvantageous, or selectively neutral depending on its context. In addition, there might be a genetic basis that regulates magnitude of SGE, which is often referred to as "modifier genes," but little is known about the conditions under which such an SGE-modifier gene evolves. In the present study, we conducted individual-based computer simulations to examine these conditions in a diploid model. In the simulations, we considered a single locus that determines organismal fitness for simplicity, and that SGE on the locus creates fitness variation in a stochastic manner. We also considered another locus that modifies the magnitude of SGE. Our results suggested that SGE was always deleterious in stable environments and increased the fixation probability of deleterious mutations in this model. Even under frequently changing environmental conditions, only very strong natural selection made SGE adaptive. These results suggest that the evolution of SGE-modifier genes requires strict balance among the strength of natural selection, magnitude of SGE, and frequency of environmental changes. However, the degree of dominance affected the condition under which SGE becomes advantageous, indicating a better opportunity for the evolution of SGE in different genetic models.
  • Ryutaro Miyagi, Noriyoshi Akiyama, Naoki Osada, Aya Takahashi
    Molecular Ecology 24 23 5829 - 5841 2015年11月 [査読有り][通常論文]
  • Naoki Osada
    Genes and Genetic Systems 90 135 - 145 2015年10月 [査読有り][招待有り]
  • Yasuhiro Uno, Shotaro Uehara, Sakae Kohara, Naoki Osada, Norie Murayama, Hiroshi Yamazaki
    Molecular Biology Reports 42 7 1149 - 1155 2015年07月 [査読有り][通常論文]
  • Shigeki Nakagome, Takehiro Sato, Hajime Ishida, Tsunehiko Hanihara, Tetsutaro Yamaguchi, Ryosuke Kimura, Shuhei, Mano, Hiroki Oota
    Molecular Biology and Evolution 32 1533 - 1543 2015年06月 [査読有り][通常論文]
  • Chao-Li Huang, Pei-Hua Pu, Hao-Jen Huang, Huang-Mo Sung, Hung-Jiun Liaw, Yi-Min Chen, Chien-Ming Chen, Ming-Ban Huang, Naoki Osada, Takashi Gojobori, Tun-Wen Pai, Yu-Tin Chen, Chi-Chuan Hwang, Tzen-Yuh Chiang
    BMC Genomics 16 188  2015年03月 [査読有り][通常論文]
  • Katsuhiko Mineta, Tomotaka Matsumoto, Naoki Osada, Hitoshi Araki
    Gene 562 16 - 21 2015年03月 [査読有り][通常論文]
  • Naoki Osada, Nilmini Hettiarachchi, Isaac Adeyemi Babarinde, Naruya Saitou, Antoine Blancher
    Genome Biology and Evolution 7 821 - 830 2015年03月 [査読有り][通常論文]
  • Chao-Li Huang, Chuan-Wen Ho, Yu-Chung Chiang, Yasumasa Shigemoto, Tsai-Wen Hsu, Chi-Chuan Hwang, Xue-Jun Ge, Charles Chen, Tai-Han Wu, Chang-Hung Chou, Hao-Jen Huang, Takashi Gojobori, Naoki Osada, Tzen-Yuh Chiang
    PLANT JOURNAL 80 5 834 - 847 2014年12月 [査読有り][通常論文]
     
    Young incipient species provide ideal materials for untangling the process of ecological speciation in the presence of gene flow. The Miscanthus floridulus/sinensis complex exhibits diverse phenotypic and ecological differences despite recent divergence (approximately 1.59million years ago). To elucidate the process of genetic differentiation during early stages of ecological speciation, we analyzed genomic divergence in the Miscanthus complex using 72 randomly selected genes from a newly assembled transcriptome. In this study, rampant gene flow was detected between species, estimated as M=3.36x10(-9) to 1.20x10(-6), resulting in contradicting phylogenies across loci. Nevertheless, beast analyses revealed the species identity and the effects of extrinsic cohesive forces that counteracted the non-stop introgression. As expected, early in speciation with gene flow, only 3-13 loci were highly diverged; two to five outliers (approximately 2.78-6.94% of the genome) were characterized by strong linkage disequilibrium, and asymmetrically distributed among ecotypes, indicating footprints of diversifying selection. In conclusion, ecological speciation of incipient species of Miscanthus probably followed the parapatric model, whereas allopatric speciation cannot be completely ruled out, especially between the geographically isolated northern and southern M.sinensis, for which no significant gene flow across oceanic barriers was detected. Divergence between local ecotypes in early-stage speciation began at a few genomic regions under the influence of natural selection and divergence hitchhiking that overcame gene flow.
  • Naoki Osada, Arihiro Kohara, Toshiyuki Yamaji, Noriko Hirayama, Fumio Kasai, Tsuyoshi Sekizuka, Makoto Kuroda, Kentaro Hanada
    DNA RESEARCH 21 6 673 - 683 2014年12月 [査読有り][通常論文]
     
    Continuous cell lines that originate from mammalian tissues serve as not only invaluable tools for life sciences, but also important animal cell substrates for the production of various types of biological pharmaceuticals. Verocells are susceptible to various types of microbes and toxins and have widely contributed to not only microbiology, but also the production of vaccines for human use. We here showed the genome landscape of a Vero cell line, in which 25,877 putative protein-coding genes were identified in the 2.97-Gb genome sequence. A homozygous similar to 9-Mb deletion on chromosome 12 caused the loss of the type I interferon gene cluster and cyclin-dependent kinase inhibitor genes in Vero cells. In addition, an similar to 59-Mb loss of heterozygosity around this deleted region suggested that the homozygosity of the deletion was established by a large-scale conversion. Moreover, a genomic analysis of Vero cells revealed a female Chlorocebus sabaeus origin and proviral variations of the endogenous simian type D retrovirus. These results revealed the genomic basis for the non-tumourigenic permanent Vero cell lineage susceptible to various pathogens and will be useful for generating new sub-lines and developing new tools in the quality control of Vero cells.
  • Tomoyoshi Komiyama, Hisakazu Iwama, Naoki Osada, Yoji Nakamura, Hiroyuki Kobayashi, Yoshio Tateno, Takashi Gojobori
    PLOS ONE 9 7 e101778  2014年07月 [査読有り][通常論文]
     
    The chicken domestication process represents a typical model of artificial selection, and gives significant insight into the general understanding of the influence of artificial selection on recognizable phenotypes. Two Japanese domesticated chicken varieties, the fighting cock (Shamo) and the long-crowing chicken (Naganakidori), have been selectively bred for dramatically different phenotypes. The former has been selected exclusively for aggressiveness and the latter for long crowing with an obedient sitting posture. To understand the particular mechanism behind these genetic changes during domestication, we investigated the degree of genetic differentiation in the aforementioned chickens, focusing on dopamine receptor D2, D3, and D4 genes. We studied other ornamental chickens such as Chabo chickens as a reference for comparison. When genetic differentiation was measured by an index of nucleotide differentiation (N-ST) newly devised in this study, we found that the N-ST value of DRD4 for Shamo (0.072) was distinctively larger than those of the other genes among the three populations, suggesting that aggressiveness has been selected for in Shamo by collecting a variety of single nucleotide polymorphisms. In addition, we found that in DRD4 in Naganakidori, there is a deletion variant of one proline at the 24th residue in the repeat of nine prolines of exon 1. We thus conclude that artificial selection has operated on these different kinds of genetic variation in the DRD4 genes of Shamo and Naganakidori so strongly that the two domesticated varieties have differentiated to obtain their present opposite features in a relatively short period of time.
  • Hiromitsu Kono, Masaru Tamura, Naoki Osada, Hitoshi Suzuki, Kuniya Abe, Kazuo Moriwaki, Kunihiro Ohta, Toshihiko Shiroishi
    DNA RESEARCH 21 3 315 - 326 2014年06月 [査読有り][通常論文]
     
    PR/SET domain containing 9 (Prdm9) mediates histone modifications such as H3K4me3 and marks hotspots of meiotic recombination. In many mammalian species, the Prdm9 gene is highly polymorphic. Prdm9 polymorphism is assumed to play two critical roles in evolution: to diversify the spectrum of meiotic recombination hotspots and to cause male hybrid sterility, leading to reproductive isolation and speciation. Nevertheless, information about Prdm9 sequences in natural populations is very limited. In this study, we conducted a comprehensive population survey on Prdm9 polymorphism in the house mouse, Mus musculus. Overall M. musculus Prdm9 displays an extraordinarily high level of polymorphism, particularly in regions encoding zinc finger repeats, which recognize recombination hotspots. Prdm9 alleles specific to various M. musculus subspecies dominate in subspecies territories. Moreover, introgression into other subspecies territories was found for highly divergent Prdm9 alleles associated with t-haplotype. The results of our phylogeographical analysis suggest that the requirement for hotspot diversity depends on geographical range and time span in mouse evolution, and that Prdm9 polymorphism has not been maintained by a simple balanced selection in the population of each subspecies.
  • Zhenxin Fan, Guang Zhao, Peng Li, Naoki Osada, Jinchuan Xing, Yong Yi, Lianming Du, Pedro Silva, Hongxing Wang, Ryuichi Sakate, Xiuyue Zhang, Huailiang Xu, Bisong Yue, Jing Li
    MOLECULAR BIOLOGY AND EVOLUTION 31 6 1475 - 1489 2014年06月 [査読有り][通常論文]
     
    Macaques are the most widely distributed nonhuman primates and used as animal models in biomedical research. The availability of full-genome sequences from them would be essential to both biomedical and primate evolutionary studies. Previous studies have reported whole-genome sequences from rhesus macaque (Macaca mulatta) and cynomolgus macaque (M. fascicularis, CE), both of which belong to the fascicularis group. Here, we present a 37-fold coverage genome sequence of the Tibetan macaque (M. thibetana; TM). TM is an endemic species to China belonging to the sinica group. On the basis of mapping to the rhesus macaque genome, we identified approximately 11.9 million single-nucleotide variants), of which 3.9 million were TM specific, as assessed by comparison two Chinese rhesus macaques (CR) and two CE genomes. Some genes carried TM-specific homozygous nonsynonymous variants (TSHNVs), which were scored as deleterious in human by both PolyPhen-2 and SIFT (Sorting Tolerant From Intolerant) and were enriched in the eye disease genes. In total, 273 immune response and disease-related genes carried at least one TSHNV. The heterozygosity rates of two CRs (0.002617 and 0.002612) and two CEs (0.003004 and 0.003179) were approximately three times higher than that of TM (0.000898). Polymerase chain reaction resequencing of 18 TM individuals showed that 29 TSHNVs exhibited high allele frequencies, thus confirming their low heterozygosity. Genome-wide genetic divergence analysis demonstrated that TM was more closely related to CR than to CE. We further detected unusual low divergence regions between TM and CR. In addition, after applying statistical criteria to detect putative introgression regions (PIRs) in the TM genome, up to 239,620 kb PIRs (8.84% of the genome) were identified. Given that TM and CR have overlapping geographical distributions, had the same refuge during the Middle Pleistocene, and show similar mating behaviors, it is highly likely that there was an ancient introgression event between them. Moreover, demographic inferences revealed that TM exhibited a similar demographic history as other macaques until 0.5 Ma, but then it maintained a lower effective population size until present time. Our study has provided new insight into the macaque evolutionary history, confirming hybridization events between macaque species groups based on genome-wide data.
  • Naoki Osada
    Frontiers in Ecology and Evolution 2 7  2014年04月 [査読有り][通常論文]
  • Naoki Osada, Shigeki Nakagome, Shuhei Mano, Yosuke Kameoka, Ichiro Takahashi, Keiji Terao
    GENETICS 195 3 1027 - + 2013年11月 [査読有り][通常論文]
     
    The ratio of genetic diversity on X chromosomes relative to autosomes in organisms with XX/XY sex chromosomes could provide fundamental insight into the process of genome evolution. Here we report this ratio for 24 cynomolgus monkeys (Macaca fascicularis) originating in Indonesia, Malaysia, and the Philippines. The average X/A diversity ratios in these samples was 0.34 and 0.20 in the Indonesian-Malaysian and Philippine populations, respectively, considerably lower than the null expectation of 0.75. A Philippine population supposed to derive from an ancestral population by founding events showed a significantly lower ratio than the parental population, suggesting a demographic effect for the reduction. Taking sex-specific mutation rate bias and demographic effect into account, expected X/A diversity ratios generated by computer simulations roughly agreed with the observed data in the intergenic regions. In contrast, silent sites in genic regions on X chromosomes showed strong reduction in genetic diversity and the observed X/A diversity ratio in the genic regions cannot be explained by mutation rate bias and demography, indicating that natural selection also reduces the level of polymorphism near genes. Whole-genome analysis of a female cynomolgus monkey also supported the notion of stronger reduction of genetic diversity near genes on the X chromosome.
  • Hisayuki Nomiyama, Naoki Osada, Osamu Yoshie
    GENES TO CELLS 18 1 1 - 16 2013年01月 [査読有り][通常論文]
     
    The genes involved in host defences are known to undergo rapid evolution. Therefore, it is often difficult to assign orthologs in multigene families among various vertebrate species. Chemokines are a large family of small cytokines that orchestrate cell migration in health and disease. Herein, we have surveyed the genomes of 18 representative vertebrate species for chemokine genes and identified a total of 553 genes. We have determined their orthologous relationships and classified them in accordance with the current systematic chemokine nomenclature system. Our study reveals an interesting evolutionary history that gave origin and diversification to the vertebrate chemokine superfamily.
  • Hiroshi Akashi, Naoki Osada, Tomoko Ohta
    GENETICS 192 1 15 - U43 2012年09月 [査読有り][招待有り]
     
    The "nearly neutral" theory of molecular evolution proposes that many features of genomes arise from the interaction of three weak evolutionary forces: mutation, genetic drift, and natural selection acting at its limit of efficacy. Such forces generally have little impact on allele frequencies within populations from generation to generation but can have substantial effects on long-term evolution. The evolutionary dynamics of weakly selected mutations are highly sensitive to population size, and near neutrality was initially proposed as an adjustment to the neutral theory to account for general patterns in available protein and DNA variation data. Here, we review the motivation for the nearly neutral theory, discuss the structure of the model and its predictions, and evaluate current empirical support for interactions among weak evolutionary forces in protein evolution. Near neutrality may be a prevalent mode of evolution across a range of functional categories of mutations and taxa. However, multiple evolutionary mechanisms (including adaptive evolution, linked selection, changes in fitness-effect distributions, and weak selection) can often explain the same patterns of genome variation. Strong parameter sensitivity remains a limitation of the nearly neutral model, and we discuss concave fitness functions as a plausible underlying basis for weak selection.
  • Chao-Li Huang, Cheng-Yu Hung, Yu-Chung Chiang, Chi-Chuan Hwang, Tsai-Wen Hsu, Chi-Chun Huang, Kuo-Hsiang Hung, Kun-Chan Tsai, Kuo-Hsiung Wang, Naoki Osada, Barbara Anna Schaal, Tzen-Yuh Chiang
    PLANT JOURNAL 70 5 769 - 782 2012年06月 [査読有り][通常論文]
     
    Asian rice, Oryza sativa, consists of two major subspecies, indica and japonica, which are physiologically differentiated and adapted to different latitudes. Genes for photoperiod sensitivity are likely targets of selection along latitude. We examined the footprints of natural and artificial selections for four major genes of the photoperiod pathway, namely PHYTOCHROME B (PhyB), HEADING DATE 1 (Hd1), HEADING DATE 3a (Hd3a), and EARLY HEADING DATE 1 (Ehd1), by investigation of the patterns of nucleotide polymorphisms in cultivated and wild rice. Geographical subdivision between tropical and subtropical O. rufipogon was found for all of the photoperiod genes in plants divided by the Tropic of Cancer (TOC). All of these genes, except for PhyB, were characterized by the existence of clades that split a long time ago and that corresponded to latitudinal subdivisions, and revealed a likely diversifying selection. Ssp. indica showed close affinity to tropical O. rufipogon for all genes, while ssp. japonica, which has a much wider range of distribution, displayed complex patterns of differentiation from O. rufipogon, which reflected various agricultural needs in relation to crop yield. In japonica, all genes, except Hd3a, were genetically differentiated at the TOC, while geographical subdivision occurred at 31 degrees N in Hd3a, probably the result of varying photoperiods. Many other features of the photoperiod genes revealed domestication signatures, which included high linkage disequilibrium (LD) within genes, the occurrence of frequent and recurrent non-functional Hd1 mutants in cultivated rice, crossovers between subtropical and tropical alleles of Hd1, and significant LD between Hd1 and Hd3a in japonica and indica.
  • Chi-Chun Huang, Kuo-Hsiang Hung, Wei-Kuang Wang, Chuan-Wen Ho, Chao-Li Huang, Tsai-Wen Hsu, Naoki Osada, Chi-Chuan Hwang, Tzen-Yuh Chiang
    GENE 499 1 194 - 201 2012年05月 [査読有り][通常論文]
     
    Recovering the genetic divergence between species is one of the major interests in the evolutionary biology. It requires accurate estimation of the neutral substitution rates. Arabidopsis thaliana, the first whole-genome sequenced plant, and its out-crossing relatives provide an ideal model for examining the split between sister species. In the study, rates of molecular evolution at markers frequently used for systematics and population genetics, including 14 nuclear genes spanning most chromosomes, three noncoding regions of chloroplast genome, and one intron of mitochondrial genome. between A. thaliana and four relatives were estimated. No deviation from neutrality was detected in the genes examined. Based on the known divergence between A. thaliana and its sisters about 8.0-17.6 MYA, evolutionary rates of the eighteen genes were estimated. Accordingly, the ratio of rates of synonymous substitutions among mitochondrial, chloroplast and nuclear genes was calculated with an average and 95% confidence interval of 1 (0.25-1.75): 15.77 (7.48-114.09): 74.79 (36.27-534.61). Molecular evolutionary rates of nuclear genes varied, with a range of 0.383-0.856 x 10(-8) for synonymous substitutions per site per year and 0.036-0.081 x 10(-9) for nonsynonymous substitutions per site per year. Compared with orthologs in Populus, a long life-span tree, genes in Arabidopsis evolved faster in an order of magnitude at the gene level, agreeing with a generation time hypothesis. The estimated substitution rates of these genes can be used as a reference for molecular dating. (C) 2012 Elsevier B.V. All rights reserved.
  • Atsunori Higashino, Ryuichi Sakate, Yosuke Kameoka, Ichiro Takahashi, Makoto Hirata, Reiko Tanuma, Tohru Masui, Yasuhiro Yasutomi, Naoki Osada
    GENOME BIOLOGY 13 7 R58  2012年 [査読有り][通常論文]
     
    Background: The genetic background of the cynomolgus macaque (Macaca fascicularis) is made complex by the high genetic diversity, population structure, and gene introgression from the closely related rhesus macaque (Macaca mulatta). Herein we report the whole-genome sequence of a Malaysian cynomolgus macaque male with more than 40-fold coverage, which was determined using a resequencing method based on the Indian rhesus macaque genome. Results: We identified approximately 9.7 million single nucleotide variants (SNVs) between the Malaysian cynomolgus and the Indian rhesus macaque genomes. Compared with humans, a smaller nonsynonymous/synonymous SNV ratio in the cynomolgus macaque suggests more effective removal of slightly deleterious mutations. Comparison of two cynomolgus (Malaysian and Vietnamese) and two rhesus (Indian and Chinese) macaque genomes, including previously published macaque genomes, suggests that Indochinese cynomolgus macaques have been more affected by gene introgression from rhesus macaques. We further identified 60 nonsynonymous SNVs that completely differentiated the cynomolgus and rhesus macaque genomes, and that could be important candidate variants for determining species-specific responses to drugs and pathogens. The demographic inference using the genome sequence data revealed that Malaysian cynomolgus macaques have experienced at least three population bottlenecks. Conclusions: This list of whole-genome SNVs will be useful for many future applications, such as an array-based genotyping system for macaque individuals. High-quality whole-genome sequencing of the cynomolgus macaque genome may aid studies on finding genetic differences that are responsible for phenotypic diversity in macaques and may help control genetic backgrounds among individuals.
  • Naoki Osada, Hiroshi Akashi
    MOLECULAR BIOLOGY AND EVOLUTION 29 1 337 - 346 2012年01月 [査読有り][通常論文]
     
    Accelerated rates of mitochondrial protein evolution have been proposed to reflect Darwinian coadaptation for efficient energy production for mammalian flight and brain activity. However, several features of mammalian mtDNA (absence of recombination, small effective population size, and high mutation rate) promote genome degradation through the accumulation of weakly deleterious mutations. Here, we present evidence for "compensatory" adaptive substitutions in nuclear DNA- (nDNA) encoded mitochondrial proteins to prevent fitness decline in primate mitochondrial protein complexes. We show that high mutation rate and small effective population size, key features of primate mitochondrial genomes, can accelerate compensatory adaptive evolution in nDNA-encoded genes. We combine phylogenetic information and the 3D structure of the cytochrome c oxidase (COX) complex to test for accelerated compensatory changes among interacting sites. Physical interactions among mtDNA- and nDNA-encoded components are critical in COX evolution; amino acids in close physical proximity in the 3D structure show a strong tendency for correlated evolution among lineages. Only nuclear-encoded components of COX show evidence for positive selection and adaptive nDNA-encoded changes tend to follow mtDNA-encoded amino acid changes at nearby sites in the 3D structure. This bias in the temporal order of substitutions supports compensatory weak selection as a major factor in accelerated primate COX evolution.
  • Alice Aarnink, Pol-Andre Apoil, Ichiro Takahashi, Naoki Osada, Antoine Blancher
    IMMUNOGENETICS 63 11 703 - 713 2011年11月 [査読有り][通常論文]
     
    We characterized the repertoire of MHC class I transcripts of a Malaysian cynomolgus macaque by the study of EST libraries derived from the mRNA extracted from six tissues (thymus, spleen, bone marrow, liver, heart and pancreas). The MHC class I transcripts present in a lymph node of the same animal were characterized by pyrosequencing of amplified cDNA fragments (515 bp from exon 2 to the beginning of exon 4). All pyrosequence consensus sequences, but three corresponding to rare transcripts, were identical to those obtained from EST libraries. In total, we characterized 19 classical class I transcripts in the Malaysian macaque studied here. By means of high- throughput sequencing of exon 2 amplified from the genomic DNA (190 bp), we characterized 38 classical class I genes in the genome of this animal. By comparison, using the same method, we found 23 classical class I genes in the genome of a MHC homozygous Mauritian animal (H2/H2). All these results suggested that the Malaysian animal was most probably heterozygous. This study reveals that the high- throughput pyrosequencing allows not only to characterize the MHC class I transcripts but also to estimate the number of MHC class I genes in the genome of cynomolgus macaque.
  • Yasuhiro Uno, Naoki Osada
    BMC EVOLUTIONARY BIOLOGY 11 283 - 283 2011年10月 [査読有り][通常論文]
     
    Background: Elucidating the pattern of evolutionary changes in drug-metabolizing genes is an important subject not only for evolutionary but for biomedical research. We investigated the pattern of divergence and polymorphisms of macaque CYP1A1 and CYP1A2 genes, which are major drug-metabolizing genes in humans. In humans, CYP1A2 is specifically expressed in livers while CYP1A1 has a wider gene expression pattern in extrahepatic tissues. In contrast, macaque CYP1A2 is expressed at a much lower level than CYP1A1 in livers. Interestingly, a previous study has shown that Macaca fascicularis CYP1A2 harbored unusually high genetic diversity within species. Genomic regions showing high genetic diversity within species is occasionally interpreted as a result of balancing selection, where natural selection maintains highly diverged alleles with different functions. Nevertheless many other forces could create such signatures. Results: We found that the CYP1A1/2 gene copy number and orientation has been highly conserved among mammalian genomes. The signature of gene conversion between CYP1A1 and CYP1A2 was detected, but the last gene conversion event in the simian primate lineage occurred before the Catarrhini-Platyrrhini divergence. The high genetic diversity of macaque CYP1A2 therefore cannot be explained by gene conversion between CYP1A1 and CYP1A2. By surveying CYP1A2 polymorphisms in total 91 M. fascicularis and M. mulatta, we found several null alleles segregating in these species, indicating functional constraint on CYP1A2 in macaques may have weakened after the divergence between humans and macaques. We propose that the high genetic diversity in macaque CYP1A2 is partly due to the degeneration of CpG sites, which had been maintained at a high level by purifying selection, and the rapid degeneration process was initiated by the loss of functional constraint on macaque CYP1A2. Conclusions: Our findings show that the highly polymorphic CYP1A2 gene in macaques has not been created by balancing selection but by the burst of CpG site degeneration after loss of functional constraint. Because the functional importance of CYP1A1/2 genes is different between humans and macaques, we have to be cautious in extrapolating a drug-testing data using substrates metabolized by CYP1A genes from macaques to humans, despite of their somewhat overlapping substrate specificity.
  • Koei Satoh, Akiko Iwata-Takakura, Naoki Osada, Akira Yoshikawa, Yuji Hoshi, Keiko Miyakawa, Yuko Gotanda, Masahiro Satake, Kenji Tadokoro, Hideaki Mizoguchi
    HEPATOLOGY RESEARCH 41 10 971 - 981 2011年10月 [査読有り][通常論文]
     
    Aim: In Japan, the etiology of 10-20% of cases of acute hepatitis remains unclarified. This study was conducted to verify the agent causing non-A-E hepatitis. Methods: Serum samples from 500 blood donors with elevated alanine aminotransferase (ALT) levels were screened by polymerase chain reaction using primers constructed from conserved areas of RNA virus helicase. The sequence obtained was investigated for viral properties. Results: Four blood samples were found to contain a novel DNA sequence of 9496 bp, which was designated KIs-V. KIs-V was sensitive to the restriction enzyme SalI and BstXI. Rolling-circle amplification produced an excessive amount of KIs-V DNA. In sucrose density gradient ultracentrifugation, KIs-V banded at a 1.158-g/cm(3) density. Detergent treatment increased the density of KIs-V. There was no KIs-V DNA amplification from human leukocyte DNA. Serial filtration suggested that KIs-V was included in a 30-50-nm size particle. In silico analysis revealed that KIs-V contained 13 potential genes, none of which showed homology to any viral proteins reported. One gene showed similarity to a DNA polymerase domain. Strong signals for transcription initiation and a CpG island were identified. The nucleotide composition of KIs-V showed a characteristic feature of circular DNA genomes that contain a replication origin and a terminus. In a preliminary study, KIs-V was frequently identified among hepatitis E virus antibody positive individuals with elevated ALT levels. Conclusion: A new sequence KIs-V was isolated from blood donors with elevated ALT levels. It was suggested that KIs-V is a double-stranded circular DNA genome derived from a novel category of enveloped viruses.
  • Renchao Zhou, Shaoping Ling, Wenming Zhao, Naoki Osada, Sufang Chen, Meng Zhang, Ziwen He, Hua Bao, Cairong Zhong, Bing Zhang, Xuemei Lu, David Turissini, Norman C. Duke, Jian Lu, Suhua Shi, Chung-I Wu
    MOLECULAR BIOLOGY AND EVOLUTION 28 10 2833 - 2842 2011年10月 [査読有り][通常論文]
     
    Population genetics of species living in marginal habitats could be particularly informative about the genetics of adaptation, but such analyses have not been readily feasible until recently. Sonneratia alba, a mangrove species widely distributed in the Indo-West Pacific, provides a very suitable system for the study of local adaptation. In this study, we analyzed DNA variation by pooling 71 genes from 85-100 individuals for DNA sequencing. For each of the two nearby S. alba populations, we obtained similar to 2,500 x coverage on the Illumina GA platform and for the Sanya population, an additional 5,400 x coverage on the AB SOLiD platform. For the Sanya sample, although each sequencing method called many putative single nucleotide polymorphisms, the two sets of calls did not overlap, suggesting platform-dependent errors. Conventional sequencing corroborated that each population is monomorphic. The two populations differ by 54 bp of 79,000 sites, but 90% of the variants are found in 10% of the genes. Strong local adaptation and high migration may help to explain the extensive monomorphism shared by the two populations in the presence of a small number of highly differentiated loci.
  • Naoki Osada
    PLOS ONE 6 9 e25549 - e25549 2011年09月 [査読有り][通常論文]
     
    Inferences of ancient sex-biased migration patterns using sex-linked genetic markers are usually difficult because of a stochastic process of allele fixation. Nevertheless, incongruent phylogenetic trees between different sex-linked markers and between sex-linked and autosomal markers are frequently interpreted as a signature of sex-biased migration without further statistical evaluation. I investigated the types of incongruent phylogenetic trees from which past sex-biased migration events can be statistically supported under the coalescent model. In the case of mammals, detecting a sex-biased migration pattern is not guaranteed by comparing the phylogenetic pattern of mitochondrial and Y-chromosomal loci Likewise, evidence of introgression at a mitochondrial locus, but not at autosomal loci, does not support the hypothesis of an ancient female-biased migration pattern with statistical significance. In contrast, evidence of introgression at >= 5 unlinked autosomal loci, but not at a Y-chromosomal locus, would reject the null hypothesis of a sexually equal migration ate with statistical significance. A similar argument can be made to infer a male-biased migration pattern. Furthermore, the Investigation of many recombining sex-biased markers such as X-chromosomal loci in mammals has the potential to efficiently detect ancient sex-biased demographic patterns.
  • Hisayuki Nomiyama, Naoki Osada, Osamu Yoshie
    DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 35 7 705 - 715 2011年07月 [査読有り][通常論文]
     
    Chemokines receptors are involved in the recruitment of various cell types in inflammatory and physiological conditions. There are 23 known chemokine receptor genes in the human genome. However, it is still unclear how many chemokine receptors exist in the genomes of various vertebrate species other than human and mouse. Moreover, the orthologous relationships are often obscure between the genes of higher and lower vertebrates. In order to provide a basis for a unified nomenclature system of the vertebrate chemokine receptor gene family, we have analysed the chemokine receptor genes from the genomes of 16 vertebrate species, and classify them into 29 orthologous groups using phylogenetic and comparative genomic analyses. The results reveal a continuous gene birth and death process during the vertebrate evolution and an interesting evolutionary history of the chemokine receptor genes after the emergence in agnathans. (C) 2011 Elsevier Ltd. All rights reserved.
  • Hisayuki Nomiyama, Naoki Osada, Osamu Yoshie
    CYTOKINE & GROWTH FACTOR REVIEWS 21 4 253 - 262 2010年08月 [査読有り][通常論文]
     
    Chemokines play an important role in orchestrating cell recruitment and localization in both physiological and pathological conditions. More than 44 ligands have been identified in the human genome. A significantly different set of chemokines, however, is found in the mouse genome, suggesting a rapid evolution of the chemokine system in mammalian genomes. Thus, there are lineage and even individual-specific differences in chemokine genes in mammals. Differences in the expression and function between even recently duplicated genes are also evident. In this review, we discuss how evolutionary events such as gene duplication and gene conversion have shaped the diverse arrays of chemokines in mammalian genomes. (C) 2010 Elsevier Ltd. All rights reserved.
  • Naoki Osada, Yasuhiro Uno, Katsuhiko Mineta, Yosuke Kameoka, Ichiro Takahashi, Keiji Terao
    MOLECULAR ECOLOGY 19 14 2884 - 2895 2010年07月 [査読有り][通常論文]
     
    Macaca fascicularis and Macaca mulatta are two of the most commonly used laboratory macaques, yet their genetic differences at a genome-wide level remain unclear. We analysed the multilocus DNA sequence data of 54 autosomal loci obtained from M. fascicularis samples from three different geographic origins and M. mulatta samples of Burmese origin. M. fascicularis shows high nucleotide diversity, four to five times higher than humans, and a strong geographic population structure between Indonesian-Malaysian and Philippine macaques. The pattern of divergence and polymorphism between M. fascicularis and M. mulatta shows a footprint of genetic exchange not only within their current hybrid zone but also across a wider range for more than 1 million years. However, genetic admixture may not be a random event in the genome. Whereas randomly selected genic and intergenic regions have the same evolutionary dynamics between the species, some cytochrome oxidase P450 (CYP) genes (major chemical metabolizing genes and potential target genes for local adaptation) have a significantly larger species divergence than other genes. By surveying CYP3A5 gene sequences of more than a hundred macaques, we identified three nonsynonymous single nucleotide polymorphisms that were highly differentiated between the macaques. The mosaic pattern of species divergence in the genomes may be a consequence of genetic differentiation under ecological adaptation and may be a salient feature in the genomes of nascent species under parapatry.
  • Yasuhiro Uno, Akinori Matsushita, Naoki Osada, Shotaro Uehara, Sakae Kohara, Ryoichi Nagata, Koichiro Fukuzaki, Masahiro Utoh, Norie Murayama, Hiroshi Yamazaki
    DRUG METABOLISM AND DISPOSITION 38 2 209 - 214 2010年02月 [査読有り][通常論文]
     
    Cynomolgus and rhesus macaques are frequently used in preclinical trials due to their close evolutionary relationships to humans. We conducted an initial screening for genetic variants in cynomolgus and rhesus macaque genes orthologous to human CYP3A4 and CYP3A5. Genetic screening of 78 Indochinese and Indonesian cynomolgus macaques and 34 Chinese rhesus macaques revealed a combined total of 42 CYP3A4 genetic variants, including 12 nonsynonymous variants, and 34 CYP3A5 genetic variants, including nine nonsynonymous variants. Four of these nonsynonymous variants were located at substrate recognition sites or the heme-binding region, domains essential for protein function, including c. 886G>A (V296M) and c. 1310G>A (S437N) in CYP3A4 and c. 1437C>G (N479K) and c.1310G>C (T437S) in CYP3A5. The mutant proteins of these genetic variants were expressed in Escherichia coli and purified. Metabolic activity of these proteins measured using midazolam and nifedipine as substrates showed that none of these protein variants substantially influences the drug-metabolizing capacity of CYP3A4 or CYP3A5 protein. In Indonesian cynomolgus macaques, we also found IVS3+1delG in CYP3A4 and c.625A>T in CYP3A5, with which an intact protein cannot be produced due to a frameshift generated. Screening additional genomes revealed that two of 239 animals and three of 258 animals were heterozygous for IVS3+1delG of CYP3A4 and c.625A>T of CYP3A5, respectively. Some genetic variants were unevenly distributed between Indochinese and Indonesian cynomolgus macaques and between cynomolgus and rhesus macaques. Information on genetic diversity of macaque CYP3A4 and CYP3A5 presented here could be useful for successful drug metabolism studies conducted in macaques.
  • Wei-Kuang Wang, Chuan-Wen Ho, Kuo-Hsiang Hung, Kuo-Hsiung Wang, Chi-Chun Huang, Hitoshi Araki, Chi-Chuan Hwang, Tsai-Wen Hsu, Naoki Osada, Tzen-Yuh Chiang
    NEW PHYTOLOGIST 188 2 488 - 500 2010年 [査読有り][通常論文]
     
    P>Outcrossing Arabidopsis species that diverged from their inbreeding relative Arabidopsis thaliana 5 million yr ago and display a biogeographical pattern of interspecific sympatry vs intraspecific allopatry provides an ideal model for studying impacts of gene introgression and polyploidization on species diversification. Flow cytometry analyses detected ploidy polymorphisms of 2x and 4x in Arabidopsis lyrata ssp. kamchatica of Taiwan. Genomic divergence between species/subspecies was estimated based on 98 randomly chosen nuclear genes. Multilocus analyses revealed a mosaic genome in diploid A. l. kamchatica composed of Arabidopsis halleri-like and A. lyrata-like alleles. Coalescent analyses suggest that the segregation of ancestral polymorphisms alone cannot explain the high inconsistency between gene trees across loci, and that gene introgression via diploid A. l. kamchatica likely distorts the molecular phylogenies of Arabidopsis species. However, not all genes migrated across species freely. Gene ontology analyses suggested that some nonmigrating genes were constrained by natural selection. High levels of estimated ancestral polymorphisms between A. halleri and A. lyrata suggest that gene flow between these species has not completely ceased since their initial isolation. Polymorphism data of extant populations also imply recent gene flow between the species. Our study reveals that interspecific gene flow affects the genome evolution in Arabidopsis.
  • Osada N, Hirata M, Tanuma R, Suzuki Y, Sugano S, Terao K, Kusuda J, Kameoka Y, Hashimoto K, Takahashi I
    BMC research notes 2 199  2009年09月02日 [査読有り][通常論文]
  • Noriko N Miura, Motohiko Komai, Yoshiyuki Adachi, Naoki Osada, Yosuke Kameoka, Kazuo Suzuki, Naohito Ohno
    Journal of immunology (Baltimore, Md. : 1950) 183 5 3417 - 24 2009年09月01日 [査読有り][通常論文]
     
    Candida albicans water-soluble fraction (CAWS), a mannoprotein-beta-glucan complex obtained from the culture supernatant of C. albicans NBRC1385, exhibits vasculitis-inducing activity (CAWS-vasculitis) in mice. The sensitivity to CAWS-vasculitis varies greatly among mouse strains. This study examined the factors contributing to or inhibiting CAWS-vasculitis using CAWS-vasculitis-resistant CBA/J mice and Bruton's tyrosine kinase-deficient CBA/N mice, which is a CAWS-vasculitis-sensitive strain that has the same origin as CBA/J mice. After stimulation with various kinds of pathogen-associated molecular patterns, the production of inflammatory cytokines IL-6 and IFN-gamma was induced in CBA/N mice, whereas that of immunosuppressive IL-10 was induced in CAWS-vasculitis-resistant CBA/J mice. Furthermore, the production of tissue inhibitor of metalloproteinase 1, an endogenous matrix metalloproteinase inhibitor, was observed in CBA/J mice. The results strongly suggest that the difference in the production of these cytokines is closely linked to the development of CAWS-vasculitis.
  • Atsunori Higashino, Naoki Osada, Yumiko Suto, Makoto Hirata, Yosuke Kameoka, Ichiro Takahashi, Keiji Terao
    BMC GENETICS 10 24  2009年06月 [査読有り][通常論文]
     
    Background: Cynomolgus macaques (Macaca fascicularis) are a valuable resource for linkage studies of genetic disorders, but their microsatellite markers are not sufficient. In genetic studies, a prerequisite for mapping genes is development of a genome-wide set of microsatellite markers in target organisms. A whole genome sequence and its annotation also facilitate identification of markers for causative mutations. The aim of this study is to establish hundreds of microsatellite markers and to develop an integrative cynomolgus macaque genome database with a variety of datasets including marker and gene information that will be useful for further genetic analyses in this species. Results: We investigated the level of polymorphisms in cynomolgus monkeys for 671 microsatellite markers that are covered by our established Bacterial Artificial Chromosome (BAC) clones. Four hundred and ninety-nine (74.4%) of the markers were found to be polymorphic using standard PCR analysis. The average number of alleles and average expected heterozygosity at these polymorphic loci in ten cynomolgus macaques were 8.20 and 0.75, respectively. Conclusion: BAC clones and novel microsatellite markers were assigned to the rhesus genome sequence and linked with our cynomolgus macaque cDNA database (QFbase). Our novel microsatellite marker set and genomic database will be valuable integrative resources in analyzing genetic disorders in cynomolgus macaques.
  • Shintaro Iwashita, Kentaro Nakashima, Motoki Sasaki, Naoki Osada, Si-Young Song
    GENE 435 1-2 88 - 95 2009年04月 [査読有り][通常論文]
     
    The p97bcnt/cfdp2 is a ruminant-specific gene created by a combination of gene duplication of ancestral bcnt (bucentaur) or cfdp1 (craniofacial developmental protein 1), bcnt/cfdp1, and the insertion of a retro-transposable element-1 (RTE). As a result, p97Bcnt recruits the whole apurinic/apyrimidinic endonuclease (APE)-like domain of RTE in the middle of the molecule (RTE domain) as a region encoded by an exon. In addition, p97Bcnt contains two intramolecular repeats (IRs) of 40 amino acids each in the C-terminal region, whereas Bcnt/Cfdp1 contains one IR. We have identified an additional bovine homolog with a structure highly similar to p97Bcnt, designated p97Bcnt2, which contains three IRs. p97bcnt2 is located in tandem with bcnt/cfdp1 and p97bcnt within a 177-kb range on bovine chromosome 18, a syntenic region of human The gene product is expressed as a protein with an apparent molecular mass of 102 kDa. The chromosome 16. phylogenetic tree strongly Suggests that p97bcnt-2 forms a third clade of the bcnt family and that the first duplication of the IR unit occurred prior to the divergence of p97bcnt and p97bcnt-2. To address the question of whether these bcnt members have distinct functions, we first examined the expression and localization of the p97Bcnt family members. p97Bcnt is substantially expressed in many tissues involved in responses to external and internal Stress. In the testis, p97Bcnt localizes preferentially in the nuclei of spermatozoa, while Bcnt/Cfdp1 localizes predominantly in the cytosol of Leydig cells and some spermatogenic cells, implying that at least these two molecules of the Bcnt family play different functional roles. These results provide evidence for the direct contribution of RTE to gene diversity to form gene families that may support cellular function. (C) 2009 Elsevier B.V. All rights reserved.
  • Naoki Osada, Shuhei Mano, Jun Gojobori
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 106 3 841 - 846 2009年01月 [査読有り][通常論文]
     
    Human genes responsible for inherited diseases are important for the understanding of human disease. We investigated the degree of polymorphism and divergence in the human disease genes to elucidate the effect of natural selection on human disease genes. In particular, the effect of disease dominance was incorporated into the analysis. Both dominant disease genes (DDG) and recessive disease genes (RDG) had a higher mutation rate per site and encoded longer proteins than the nondisease genes, which exposed the disease genes to a faster flux of new mutations. Using an unbiased polymorphism dataset, we found that, proportionally, RDG harbor more nonsynonymous polymorphisms compared with DDG. We estimated the selection intensity on the disease genes using polymorphism and divergence data and determined whether the different patterns of polymorphism and divergence between DDG and RDG could be explained by the difference in only dominance. Even after the dominance effect was considered, the selection intensity on RDG was significantly different from DDG, suggesting that the deleterious effect of the dominant and recessive disease mutations are fundamentally different.
  • Osada N, Innan H
    PLoS genetics 4 e1000305  12 2008年12月 [査読有り][通常論文]
  • Nomiyama H, Hieshima K, Osada N, Kato-Unoki Y, Otsuka-Ono K, Takegawa S, Izawa T, Yoshizawa A, Kikuchi Y, Tanase S, Miura R, Kusuda J, Nakao M, Yoshie O
    BMC genomics 9 222  2008年05月01日 [査読有り][通常論文]
  • Osada N, Hashimoto K, Kameoka Y, Hirata M, Tanuma R, Uno Y, Inoue I, Hida M, Suzuki Y, Sugano S, Terao K, Kusuda J, Takahashi I
    BMC genomics 9 90  2008年02月02日 [査読有り][通常論文]
  • Uno Y, Suzuki Y, Wakaguri H, Sakamoto Y, Sano H, Osada N, Hashimoto K, Sugano S, Inoue I
    FEBS letters 582 2 351 - 358 2 2008年01月02日 [査読有り][通常論文]
  • Naoki Osada
    MOLECULAR BIOLOGY AND EVOLUTION 24 8 1622 - 1626 2007年08月 [査読有り][通常論文]
     
    There is a mounting evidence for the correlation between the gene expression pattern and sequence divergence. However, little is known about the relationship between the gene expression pattern and polymorphism. We compiled the gene expression, polymorphism, and divergence data from the public databases of the human genome. The ratios of nonsynonymous (A) to synonymous (S) substitutions in polymorphism and divergence in the human genome were strongly influenced by the expression pattern and breadth of genes and showed strong correlations. Among the tissues we analyzed, the brain-expressed genes have the smallest and the liver-expressed genes have the largest proportion of amino acid changes both in polymorphism and divergence. The analysis implies that negative selection is the primary factor affecting expression-dependent gene evolution and the prevalent but nonuniform distribution of slightly deleterious mutations in the genome. Although the genes under relaxed negative selection evolved faster than the other genes, these genes are even more liable to slightly deleterious mutations in the population. On the other hand, nonneutral mutations in the highly conservative genes, such as brain-expressed and housekeeping genes, are largely deleterious and eliminated before they enter the population.
  • K. Kawabata, K. Tashiro, F. Sakurai, N. Osada, J. Kusuda, T. Hayakawa, K. Yamanishi, H. Mizuguchi
    GENE THERAPY 14 16 1199 - 1207 2007年08月 [査読有り][通常論文]
     
    Coxsackievirus and adenovirus receptor (CAR) is a member of the immunoglobulin (lg) superfamily and a component of epithelial tight junction. CAR also functions as a primary receptor for coxsackievirus B and adenovirus (Ad) infection. In this study, we report the identification of a novel protein, CAR-like soluble protein (CLSP), which is closely related to CAR. Mouse CLSP (mCLSP) was composed of 390 amino acids, including three lg domains, and showed strong homology to the lgV domain of CAR. Interestingly, mCLSP lacks a transmembrane domain, indicating that this is a soluble protein. mCLSP mRNA was detected primarily in the brain and ovary. When mCLSP cDNA was introduced into SK HEP-1 cells, which were known to be CAR positive and easily infected with Ad vector, the infection with Ad vector was severely inhibited. On the other hand, mCLSP promoted the infection with Ad vector in CAR-negative NIH3T3 cells. Furthermore, recombinant CLSP directly bound to Ad and inhibited the Ad vector-mediated transduction in SK HEP-1 cells. Computational analysis for a genome database showed that the CLSP gene is rodent-specific, and that human and bovine lack this gene. These results suggest that CLSP may play a role in the antiviral defense of the host in rodent animals.
  • Naoki Osada, Katsuyuki Hashimoto, Momoki Hirai, Jun Kusuda
    GENE 392 1-2 151 - 156 2007年05月 [査読有り][通常論文]
     
    Finding genetic novelties that may contribute to human-specific physiology and diseases is a key issue of current biomedical studies. TMEM30C is a gene containing two transmembrane (TM) domains and homologous to the yeast CDC50 family, which is related to polarized cell division. It is conserved among mammals along with two other paralogs, TMEM30A and TMEM30B. We found that TMEM30C is expressed specifically in the testis of mammals, in contrast to the relatively wide expression distributions of the other paralogs. While macaques expressed two alternative splicing isoforms which include one or two TM domains, humans and chimpanzees predominantly expressed truncated transcripts because of the mutations in the splicing and/or poly(A) signal sites. The major transcript in humans harbored non-stop ORF (open reading frame) while the chimpanzee counterpart encoded a protein with one TM domain. The difference was due to the 1-bp indel upstream of the poly(A) signal site. In addition, both the hominoids expressed minor transcripts encoding short proteins with one TM domain. Phylogenetic analysis has showed the acceleration of amino acid substitution after the human and chimpanzee divergence, which may have been caused by a recent relaxation in functional constraints or positive selection on TMEM30C. Elucidating the precise reproductive function of TMEM30C in mammals will be important to the foundation of divergence in higher primates at a molecular level. (c) 2006 Elsevier B.V. All rights reserved.
  • Hurng-Yi Wang, Huan-Chieh Chien, Naoki Osada, Katsuyuki Hashimoto, Sumio Sugano, Takashi Gojobori, Chen-Kung Chou, Shih-Feng Tsai, Chung-I Wu, C. -K. James Shen
    PLOS BIOLOGY 5 2 335 - 342 2007年02月 [査読有り][通常論文]
     
    Brain-expressed genes are known to evolve slowly in mammals. Nevertheless, since brains of higher primates have evolved rapidly, one might expect acceleration in DNA sequence evolution in their brain-expressed genes. In this study, we carried out full-length cDNA sequencing on the brain transcriptome of an Old World monkey (OWM) and then conducted three-way comparisons among (i) mouse, OWM, and human, and (ii) OWM, chimpanzee, and human. Although brain-expressed genes indeed appear to evolve more rapidly in species with more advanced brains (apes. OWM. mouse), a similar lineage effect is observable for most other genes. The broad inclusion of genes in the reference set to represent the genomic average is therefore critical to this type of analysis. Calibrated against the genomic average, the rate of evolution among brain-expressed genes is probably lower (or at most equal) in humans than in chimpanzee and OWM. Interestingly, the trend of slow evolution in coding sequence is no less pronounced among brain-specific genes, vis-a-vis brain-expressed genes in general. The human brain may thus differ from those of our close relatives in two opposite directions: (i) faster evolution in gene expression, and (ii) a likely slowdown in the evolution of protein sequences. Possible explanations and hypotheses are discussed.
  • Hisayuki Nomiyama, Kaori Otsuka-Ono, Retsu Miura, Naoki Osada, Keiji Terao, Osamu Yoshie, Jun Kusuda
    JOURNAL OF INTERFERON AND CYTOKINE RESEARCH 27 1 32 - 37 2007年01月 [査読有り][通常論文]
     
    Chemokines are a rapidly evolving cytokine gene family. Because of various genome rearrangements after divergence of primates and rodents, humans and mice have different sets of chemokine genes, with humans having members outnumbering those of mice. Here, we report the occurrence of lineage-specific chemokine gene generation or inactivation events within primates. By using human chemokine sequences as queries, we isolated a novel cynomolgus macaque CXC chemokine cDNA. The encoded chemokine, termed CXCL1L (from CXCL1-like) showed the highest similarity to human CXCL1. A highly homologous gene was also found in the rhesus macaque genome. By comparing the genome organization of the major CXC chemokine clusters among the primates, we found that one copy of the duplicated CXCL1 genes turned into a pseudogene in the hominids, whereas the gene in macaques has been maintained as a functionally active CXCL1L. In addition, cynomolgus macaque was found to contain an additional CXC chemokine highly homologous to CXCL3, termed CXCL3L (from CXCL3-like). These results demonstrate the birth-and-death process of a new gene in association with gene duplication within the primates.
  • Naoki Osada, Michael H. Kohn, Chung-I Wu
    MOLECULAR BIOLOGY AND EVOLUTION 23 8 1585 - 1591 2006年08月 [査読有り][通常論文]
     
    Nucleotide sequence polymorphisms affecting gene expression occur in the regulatory region of genes (in cis) and elsewhere in the genome (in trans). Further study is required to weigh the relative importance of cis- and trans-acting mutations in mediating gene expression differences within and between species. Here, microarray hybridization experiments were used to isolate 363 gene expression differences between the female fly head transcriptomes of 2 Drosophila melanogaster strains. One strain (French) represented the cosmopolitan M mating race and the other strain (ZS30) represented the Z mating race derived from Zimbabwe, Africa. From chromosomal substitution strains engineered from the 2 strains, we inferred that the expression differences between M and Z alleles largely could be attributed to the genotype of the chromosomes where the differentially expressed genes were located, that is, cis-regulatory polymorphisms prominently influence gene expression differences between M and Z. The effects of trans-regulatory polymorphisms were apparent yet difficult to quantity. Results have implications for models of gene regulatory evolution as well as experimental studies trying to identify the nucleotide sequence polymorphisms underlying gene expression differences between Drosophila strains.
  • S Iwashita, S Ueno, K Nakashima, SY Song, K Ohshima, K Tanaka, H Endo, J Kimura, M Kurohmaru, K Fukuta, L David, N Osada
    MOLECULAR BIOLOGY AND EVOLUTION 23 4 798 - 806 2006年04月 [査読有り][通常論文]
     
    Retrotransposable element-1 (RTE-1) is a class of long interspersed nucleotide elements that contain in its open reading frame an apurinic/apyrimidinic endonuclease domain (AP-END) and a reverse transcriptase domain. Ruminants have a clade-specific RTE-1 (BovB/RTE). The bovine bcnt gene (bucentaur or craniofacial developmental protein 1) has a duplicated paralog (bcnt(p97)) in tandem that recruited an AP-END of BovB/RTE as a coding exon (RTE exon). We obtained sequence of the bcnt region from several animals and showed that other ruminants also have the bcnt(p97) with a conserved RTE exon while camels and pigs do not. Genomic Southern analysis showed that camels and pigs have multiple bcnt-related sequences but not BovB/RTE which bovines and lesser mouse deer have abundantly. These results indicate that the bcnt gene duplication followed by the creation of bcnt(p97) including recruitment of the RTE exon occurred in the ancestral ruminant about 55 MYA. The indication of time frame is supported by a phylogenetic analysis. Taken together with a result of differential tissue expression of the two bcnt paralogs, we conclude that bcnt(p97) was created concurrently with the early radiation of BovB/RTE in an ancestral ruminant and then acquired a novel function.
  • N Osada, M Hirata, R Tanuma, J Kusuda, M Hida, Y Suzuki, S Sugano, T Gojobori, CKJ Shen, CI Wu, K Hashimoto
    MOLECULAR BIOLOGY AND EVOLUTION 22 10 1976 - 1982 2005年10月 [査読有り][通常論文]
     
    The substitution rate and structural divergence in the 5'- untranslated region ( UTR) were investigated by using human and cynomolgus monkey cDNA sequences. Due to the weaker functional constraint in the UTR than in the coding sequence, the divergence between humans and macaques would provide a good estimate of the nucleotide substitution rate and structural divergence in the 5' UTR. We found that the substitution rate in the 5' UTR ( K-5UTR) averaged approximate to 10% - 20% lower than the synonymous substitution rate ( K-s). However, both the K-5UTR and nonsynonymous substitution rate ( K-a) were significantly higher in the testicular cDNAs than in the brain cDNAs, whereas the Ks did not differ. Further, an in silico analysis revealed that 27% ( 169/ 622) of macaque testicular cDNAs had an altered exon- intron structure in the 5' UTR compared with the human cDNAs. The fraction of cDNAs with an exon alteration was significantly higher in the testicular cDNAs than in the brain cDNAs. We confirmed by using reverse transcriptase - polymerase chain reaction that about one- third ( 6/ 16) of in silico `` macaque - specific'' exons in the 5' UTR were actually macaque specific in the testis. The results imply that positive selection increased K5UTR and structural alteration rate of a certain fraction of genes as well as Ka. We found that both positive and negative selection can act on the 5' UTR sequences.
  • JA Alipaz, S Fang, N Osada, CI Wu
    AMERICAN NATURALIST 165 4 420 - 428 2005年04月 [査読有り][通常論文]
     
    We monitored the phenotypic and genotypic changes that occur when two behavioral races come into contact in laboratory populations. Drosophila melanogaster from Zimbabwe and nearby regions (Z type) show strong but asymmetric sexual isolation from their cosmopolitan counterparts ( M type). Crosses of Z females and M males do not take place readily when other choices are available. At least 15 loci are known to control Z-type mating preferences and performance. By thoroughly mixing the genomes of the two types in laboratory populations, we artificially created maximum secondary contact. Despite the strength of sexual selection favoring Z-type male characters, Z-type behavior is eliminated or greatly diminished in all 12 hybrid populations after only 60 generations. This trend is consistent with the spread of the M-type behavior throughout the world as well as a detailed analysis of fitness components. Surprisingly, in contrast with the phenotypic convergence toward the M-type, genotypic samples broadly covering the genomic regions of mapped behavioral loci show no such trend. The genome appears to be "fine grained," with adjacent loci having different evolutionary dynamics and genealogical histories.
  • N Osada, CI Wu
    GENETICS 169 1 259 - 264 2005年01月 [査読有り][通常論文]
     
    The strictly allopatric model of speciation makes definable predictions on the pattern of divergence, one of which is the uniformity in the divergence time across genomic regions. Using 345 coding and 143 intergenic sequences from the African great apes, we were able to reject the mill hypothesis that the divergence time in the coding sequences (CDSs) and intergenic sequences (IGSs) is the same between human and chimpanzee. The conclusion is further supported by the analysis of whole-genome sequences between these species. The difference suggests a prolonged period of genetic exchange during the formation of these two species. Because the analysis should be generally applicable, collecting DNA sequence data from many genomic regions between closely related species should help to settle the debate over the prevalence of the allopatric mode of speciation.
  • S Iwashita, N Osada, T Itoh, M Sezaki, K Oshima, E Hashimoto, Y Kitagawa-Arita, Takahashi, I, T Masui, K Hashimoto, W Makalowski
    MOLECULAR BIOLOGY AND EVOLUTION 20 9 1556 - 1563 2003年09月 [査読有り][通常論文]
     
    Ruminant Bent protein with a molecular mass of 97 kDa (designated p97Bcnt) includes a region derived from the endonuclease domain of a retrotransposable element RTE-1. Human and mouse Bcnt proteins lack the corresponding region but have a highly conserved 82-amino acid region at the C-terminus that is not present in p97Bcnt. By screening a bovine BAC library, we found two more bcnt-related genes: human-type bent (h-type bent) and its processed pseudogene. Whereas the pseudogene is localized on chromosome 26, both bcnt(p97) and the h-type bent genes are found on bovine chromosome 18, a synteny region of human chromosome 16 on which human BCNT is localized. Complete nucleotide sequencing of the BAC clone reveals that the bcnt(p97) and h-type bent genes are located just 6 kb apart in a tandem manner. The two h-type bent and bcnt(p97) genes are active at both the transcriptional level and the protein level. H-type bovine Bent is more like human BCNT than p97Bcnt, when compared at their N-terminal regions. However, phylogenetic analysis using the N-terminal region of the bent gene family revealed that the duplication of bovine genes occurred within the bovine lineage with significantly accelerated substitution in bcnt(p97). This acceleration was not ascribed definitely to positive selection. After duplication, one of the bovine bent genes recruited the endonuclease domain of an intronic RTE-1 repeat accompanied by the accelerated substitution at the 5'-ORF, resulting in creation of a novel type of Bcnt protein in bovine.
  • FM Mesak, N Osada, K Hashimoto, QY Liu, CE Ng
    BMC GENOMICS 4 32  2003年08月 [査読有り][通常論文]
     
    Background: As part of our investigation into the genetic basis of tumor cell radioresponse, we have isolated several clones with a wide range of responses to X-radiation (XR) from an unirradiated human colorectal tumor cell line, HCT116. Using human cDNA microarrays, we recently identified a novel gene that was down-regulated by two-fold in an XR-resistant cell clone, HCT116(Clone2_ XRR). We have named this gene as X-ray radiation resistance associated 1 (XRRA1) ( GenBank BK000541). Here, we present the first report on the molecular cloning, genomic characterization and over-expression of the XRRA1 gene. Results: We found that XRRA1 was expressed predominantly in testis of both human and macaque. cDNA microarray analysis showed three-fold higher expression of XRRA1 in macaque testis relative to other tissues. We further cloned the macaque XRRA1 cDNA ( GenBank AB072776) and a human XRRA1 splice variant from HCT116(Clone2_ XRR) (GenBank AY163836). In silico analysis revealed the full-length human XRRA1, mouse, rat and bovine Xrra1 cDNAs. The XRRA1 gene comprises 11 exons and spans 64 kb on chromosome 11q13.3. Human and macaque cDNAs share 96% homology. Human XRRA1 cDNA is 1987 nt long and encodes a protein of 559 aa. XRRA1 protein is highly conserved in human, macaque, mouse, rat, pig, and bovine. GFP-XRRA1 fusion protein was detected in both the nucleus and cytoplasm of HCT116 clones and COS-7 cells. Interestingly, we found evidence that COS-7 cells which over-expressed XRRA1 lacked Ku86 (Ku80, XRCC5), a non-homologous end joining (NHEJ) DNA repair molecule, in the nucleus. RT-PCR analysis showed differential expression of XRRA1 after XR in HCT116 clones manifesting significantly different XR responses. Further, we found that XRRA1 was expressed in most tumor cell types. Surprisingly, mouse Xrra1 was detected in mouse embryonic stem cells R1. Conclusions: Both XRRA1 cDNA and protein are highly conserved among mammals, suggesting that XRRA1 may have similar functions. Our results also suggest that the genetic modulation of XRRA1 may affect the XR responses of HCT116 clones and that XRRA1 may have a role in the response of human tumor and normal cells to XR. XRRA1 might be correlated with cancer development and might also be an early expressed gene.
  • R Sakate, N Osada, M Hida, S Sugano, Hayasaka, I, N Shimohira, S Yanagi, Y Suto, K Hashimoto, M Hirai
    GENOME RESEARCH 13 5 1022 - 1026 2003年05月 [査読有り][通常論文]
     
    We constructed full-length enriched cDNA libraries from chimpanzee brain, skin, and liver tissues by the oligo-capping method to establish a database of sequences of chimpanzee genes. Randomly selected clones from the libraries were subjected to one-pass sequencing from their 5'-ends. As a result, we collected 6813 chimpanzee cDNA sequences longer than 400 bp. Homology search against human mRNA sequences (RefSeq mRNAs) revealed that our collection included sequences of 1652 putative chimpanzee genes. In order to calculate the sequence identity between human and chimpanzee homologs, we constructed 5'-end consensus sequences of 226 chimpanzee genes by aligning at least three sequences for individual genes. Sequence identity was estimated by comparing these consensus sequences and the corresponding sequences of their human homologs. The average sequence identity of the 5'-end cDNAs was 99.30%. Those of the 5'-UTRs and CDSs were 98.79% and 99.42%, respectively. The results confirmed that human and chimpanzee genes are highly conserved at the nucleotide level. As for amino acids, the average sequence identity was 99.44%. The average synonymous (K(S)) and nonsynonymous (K(A)) divergences were estimated to be 1.33% and 0.28%, respectively.
  • N Osada, J Kusuda, M Hirata, R Tanuma, M Hida, S Sugano, M Hirai, K Hashimoto
    GENOMICS 79 5 657 - 662 2002年05月 [査読有り][通常論文]
     
    It is possible to assess positive selection by using the ratio of K-a (nonsynonymous substitutions per plausible nonsynonymous sites) to K-s (synonymous substitutions per plausible synonymous sites). We have searched candidate genes positively selected during primate evolution by using 5'-end sequences of 21,302 clones derived from cynomolgus monkey (Macaca fascicularis) brain cDNA libraries. Among these candidates, 10 genes that had not been shown by previous studies to undergo positive selection exhibited a K-a/K-s ratio > 1. Of the 10 candidate genes we found, 5 were included in the mitochondrial respiratory enzyme complexes, suggesting that these nuclear-encoded genes coevolved with mitochondrial-encoded genes, which have high mutation rates. The products of other candidate genes consisted of a cell-surface protein, a member of the lipocalin family, a nuclear transcription factor, and hypothetical proteins.
  • Osada N, Hida M, Kusuda J, Tanuma R, Hirata M, Hirai M, Terao K, Suzuki Y, Sugano S, Hashimoto K
    Genome biology 3 RESEARCH0006  1 2002年 [査読有り][通常論文]
  • N Osada, M Hida, J Kusuda, R Tanuma, M Hirata, Y Suto, M Hirai, K Terao, S Sugano, K Hashimoto
    BMC GENOMICS 3 36  2002年 [査読有り][通常論文]
     
    Background: In order to contribute to the establishment of a complete map of transcribed regions of the human genome, we constructed a testicular cDNA library for the cynomolgus monkey, and attempted to find novel transcripts for identification of their human homologues. Result: The full-insert sequences of 512 cDNA clones were determined. Ultimately we found 302 non-redundant cDNAs carrying open reading frames of 300 bp-length or longer. Among them, 89 cDNAs were found not to be annotated previously in the Ensembl human database. After searching against the Ensembl mouse database, we also found 69 putative coding sequences have no homologous cDNAs in the annotated human and mouse genome sequences in Ensembl. We subsequently designed a DNA microarray including 396 non-redundant cDNAs (with and without open reading frames) to examine the expression of the full-sequenced genes. With the testicular probe and a mixture of probes of 10 other tissues, 316 of 332 effective spots showed intense hybridized signals and 75 cDNAs were shown to be expressed very highly in the cynomolgus monkey testis, but not ubiquitously. Conclusions: In this report, we determined 302 full-insert sequences of cynomolgus monkey cDNAs with enough length of open reading frames to discover novel transcripts as human homologues. Among 302 cDNA sequences, human homologues of 89 cDNAs have not been predicted in the annotated human genome sequence in the Ensembl. Additionally, we identified 75 dominantly expressed genes in testis among the full-sequenced clones by using a DNA microarray. Our cDNA clones and analytical results will be valuable resources for future functional genomic studies.
  • Yutaka Suzuki, Tatsuhiko Tsunoda, Jun Sese, Hirotoshi Taira, Junko Mizushima-Sugano, Hiroko Hata, Toshio Ota, Takao Isogai, Naoki Osada, Katsuyuki Hashimoto, Toshihiro Tanaka, Yusuke Nakamura, Akira Suyama, Yoshiyuki Sakai, Shinichi Morishita, Kousaku Okubo, Sumio Sugano
    Genome Res. 11 677 - 684 2001年 [査読有り][通常論文]
  • Naoki Osada, Munetomo Hida, Jun Kusuda, Reiko Tanuma, Kanako Iseki, Makoto Hirata, Yumiko Suto, Momoki Hirai, Keiji Terao, Yutaka Suzuki, Sumio Sugano, Katsuyuki Hashimoto
    Gene 275 1 31 - 37 2001年 [査読有り][通常論文]
  • N Osada, J Kusuda, Y Suzuki, S Sugano, K Hashimoto
    JOURNAL OF HUMAN GENETICS 45 6 374 - 377 2000年 [査読有り][通常論文]
     
    The Borg (binder of Rho GTPases) family proteins interact with CDC42 and TC10 in a guanosine triphosphate (GTP)-dependent manner. We have isolated a full-length cDNA of the mouse Borg4 gene, which is a member of this family. Sequence analysis revealed that this gene encoded a putative 349-amino acid protein. By reverse transcription - coupled polymerase chain reaction (RT-PCR) analysis, we observed that Borg4 was er;pressed ubiquitously in adult tissues. Additionally, we determined the entire cDNA sequence of the putative human Borg4 orthologue, By fluorescence in situ hybridization, mouse Borg4 and the putative human orthologue have been assigned to mouse chromosome 11E and human chromosome 17q24-25, which has been described as syntenic to the mouse region.

書籍

講演・口頭発表等

  • 霊長類種間における遺伝子浸透様式の解析  [通常講演]
    長田直樹
    ヤポネシアゲノム若手研究集会 2019年01月 口頭発表(一般)
  • ゲノムからたどる人類進化の歴史  [招待講演]
    長田直樹
    名古屋大学遺伝子実験施設公開セミナー「ゲノム解析が見える化する生命の成り立ち」 2018年12月 公開講演,セミナー,チュートリアル,講習,講義等
  • 性による移住率の偏りをゲノムデータから推定する  [招待講演]
    長田直樹
    日本人類学会大会公開シンポジウム:DNAからみたヒトの進化 2018年10月 口頭発表(招待・特別) 静岡県三島市
  • 旧世界ザルゲノムに存在する内在性サルレトロウィルス(SERV)配列の探索と分子系統解析  [通常講演]
    池田昌輝, 里村和浩, 関塚剛史, 花田賢太郎, 遠藤俊徳, 長田直樹
    第90回日本遺伝学会 2018年09月 口頭発表(一般)
  • Dissecting genetic and epigenetic gene expression regulatory variations in diploid organisms  [招待講演]
    長田直樹
    14th Japanese-German Frontiers of Science Symposium 2018年09月 ポスター発表
  • ゲノム進化解析ソフトウェアの使い方  [通常講演]
    長田直樹
    第2回木村資生記念進化学セミナー 2018年09月 公開講演,セミナー,チュートリアル,講習,講義等
  • 集団遺伝学とゲノム進化学  [招待講演]
    長田直樹
    第11回生物学基礎論研究会特別講演 2017年09月 口頭発表(招待・特別)
  • 環境変動と集団サイズ変動の関係を考える  [通常講演]
    長田直樹
    日本列島(ヤポネシア)人のゲノム歴史学 2017年08月 口頭発表(一般)
  • Quantifying genetic and epigenetic control of gene expression in Drosophila and mice  [招待講演]
    長田直樹
    The 5th international symposium “Frontier Science in Ecology, Genetics and Genomics” 2017年03月 口頭発表(招待・特別)
  • 集団遺伝学データ解析  [招待講演]
    長田直樹
    ゲノム多様性データの統計解析ワークショップ 2016年12月 公開講演,セミナー,チュートリアル,講習,講義等
  • Genomics of non-human primates: application to biomedical studies  [招待講演]
    Naoki Osada
    2016 HU/SNU joint symposium 2016年11月 口頭発表(招待・特別)
  • Population genomics of non-human primates: a case of Mauritian cynomolgus macaques (Macaca fascicularis)  [通常講演]
    Naoki Osada, Soichi Sakurai
    5th Asian Primate Symposium 2016年10月 口頭発表(一般)
  • An impact of population bottleneck on genomes: a case of Mauritian cynomolgus macaques (Macaca fascicularis)  [招待講演]
    Naoki Osada
    13th Japanese-German Frontiers of Science Symposium 2016年10月 ポスター発表
  • 集団遺伝学データ解析  [通常講演]
    長田直樹
    ゲノム多様性データの統計解析ワークショップ 2015年12月 公開講演,セミナー,チュートリアル,講習,講義等 総合研究大学院大学葉山キャンパス
  • Genetic architecture of gene expression variation in fruit flies  [通常講演]
    Naoki Osada
    12th Japanese-German Frontiers of Science Symposium 2015年10月 ポスター発表
  • モーリシャス島産カニクイザルの全ゲノムシークエンス解析  [通常講演]
    長田直樹, Hettiarachchi Nilmini, Babarinde Isaac Adeyemi, 斎藤成也, Blancher Antoine
    第31回日本霊長類学会大会 2015年07月 口頭発表(一般)
  • ボトルネックがゲノムに与える現象の解析:モーリシャス産カニクイザルを例に  [通常講演]
    長田直樹
    遺伝研研究集会「ビッグデータ時代の分子進化」 2015年06月 口頭発表(招待・特別)
  • 集団遺伝学データ解析:ABCのABC  [通常講演]
    長田直樹
    ゲノム多様性データの統計解析ワークショップ 2014年12月 公開講演,セミナー,チュートリアル,講習,講義等
  • Challenge of population genomics in non-model organisms  [通常講演]
    長田直樹
    Frontiers in Genomic Research 2014年12月 口頭発表(基調)
  • 木村先生の研究に関連した、私の二つの研究トピック: 優性度による選択圧の違いと補完的進化  [通常講演]
    長田直樹
    木村資生博士生誕90周年記念シンポジウム 2014年11月 シンポジウム・ワークショップパネル(指名)
  • Compensatory Evolution  [通常講演]
    長田直樹
    EvoDevo・PopGenの融合アプローチから明らかになる適応進化の新局面 2014年10月 シンポジウム・ワークショップパネル(指名)
  • 日本遺伝学会奨励賞受賞講演「ゲノム情報と進化理論の統合による進化機構の解明」  [通常講演]
    長田直樹
    第86回日本遺伝学会大会 2014年09月 口頭発表(招待・特別)
  • Allele-specific gene expression among Drosophila melanogaster hybrid lines revealed abundant cis-regulatory mutations  [通常講演]
    長田直樹
    国立遺伝学研究所研究会:ゲノム進化分野におけるビッグデータ情報解析の新展開 2014年03月 口頭発表(一般)
  • Finding evidence for weak compensatory evolution  [通常講演]
    Naoki Osada, Hiroshi Akashi
    SMBE Satellite Meeting/NIG International Workshop: The Causes of Genome Evolution 2014年03月 口頭発表(招待・特別)
  • 帰無モデルとしての中立説と歴史推定  [通常講演]
    長田直樹
    統計数理研究所研究集会:ゲノム多様性のデータ解析 2013年12月 口頭発表(招待・特別)
  • Dissecting regulatory mechanisms of transcriptome variation in Drosophila melanogaster  [通常講演]
    Naoki Osada
    Seminar at Academia Sinica 2013年11月 口頭発表(招待・特別)
  • Dissecting regulatory mechanisms of transcriptome variation in Drosophila melanogaster  [通常講演]
    Naoki Osada
    ISEGB2013 2013年11月 口頭発表(招待・特別)
  • 霊長類のゲノム進化  [通常講演]
    長田直樹
    日本人類学会大会 2013年11月 口頭発表(一般)
  • キイロショウジョウバエにおける集団内でのcisおよびtrans遺伝子発現変異の定量  [通常講演]
    長田直樹, 宮城竜太郎, 高橋文
    日本遺伝学会大会 2013年09月 口頭発表(一般)
  • Finding the factors of reduced genetic diversity on X chromosomes of Macaca fascicularis  [通常講演]
    Naoki Osada, Shigeki Nakagome, Shuhei Mano, Yosuke Kameoka, Ichiro Takahashi, Keiji Terao
    SMBE2013 2013年07月 ポスター発表
  • Finding evidence for weak compensatory evolution  [通常講演]
    長田直樹
    NIG Collaborative Workshop: Evolution of Junk DNAs 2013年06月 口頭発表(一般)
  • ヒトゲノムの進化における自然選択と遺伝的浮動の役割  [通常講演]
    長田直樹
    インシリコ・メガバンク研究会 2013年05月 口頭発表(招待・特別)
  • Evolution of rice photoperiod genes  [通常講演]
    長田直樹
    NIG collaborative research meeting: Evolutionary Genetics and Proteomics of Natural Resources in Asia 2013年02月 口頭発表(一般)
  • Ecological and Evolutionary Genomics of non-model organisms in Asia  [通常講演]
    長田直樹
    CKJ meeting: Genomics, Proteomics, and Bioinformatics with the Asian Perspective 2012年12月 口頭発表(一般)
  • 実験用霊長類のゲノムとその多様性  [通常講演]
    長田直樹
    霊長類医科学研究フォーラム 2012年11月 口頭発表(招待・特別)
  • 霊長類でのX染色体と常染色体との遺伝的多様性の比について  [通常講演]
    長田直樹
    日本人類学会大会 2012年11月 口頭発表(一般)
  • ゲノムの分岐パターンから探る-歴史,種分化,適応  [通常講演]
    長田直樹
    みちのく進化生物セミナー 2012年10月 口頭発表(招待・特別)
  • Genetic diversity of humans and nonhuman primates and its evolutionary implications  [通常講演]
    Naoki Osada
    Seminar at Academia Sinica 2012年09月 口頭発表(招待・特別)
  • Inference of population history from genomic data  [通常講演]
    Naoki Osada
    Arabidopsis symposium 2012年09月 口頭発表(招待・特別)
  • ゲノム情報を用いた集団の歴史の推定:霊長類や植物の例  [通常講演]
    長田直樹
    統計数理研究所研究集会:生物集団に関する遺伝データと集団遺伝学 2012年08月 口頭発表(一般)
  • Compensatory Evolution between Mitochondrial and Nuclear Genomes  [通常講演]
    Naoki Osada
    Okazaki Biological Conference 8 (OBC8) 2012年03月 口頭発表(招待・特別)
  • Inference of natural selection by stratifying individual genome sequences  [通常講演]
    長田直樹
    国立遺伝学研究所研究会:ゲノム多様性研究における革新的な知的発見のための戦略~次世代シーケンサーを用いたゲノム多様性研究における今後の課題~ 2012年03月 口頭発表(一般)
  • Genetic diversity and population history of macaque monkeys  [通常講演]
    Naoki Osada
    Genomic Conservation and Diversity of Organisms: Beyond the NGS time of Life Science 2011年12月 口頭発表(招待・特別)
  • Inference of population history using a single genome data  [通常講演]
    長田直樹
    日本分子生物学会年会 2011年12月 口頭発表(一般)
  • 多座位データを用いたゲノムヒストリーの推定  [通常講演]
    長田直樹
    統計数理研究所共同利用重点型研究による研究集会:ゲノムの多様性,進化,疾患に関わる話題についての講演 2011年12月 口頭発表(招待・特別)
  • メタゲノム解析とその応用  [通常講演]
    長田直樹
    メタゲノム解析を利用した下水道情報網基盤構築に関する研究集会 2011年11月 口頭発表(一般)
  • 機能喪失とCpGサイトの崩壊による旧世界ザルCYP1A2遺伝子の高い遺伝的多様性  [通常講演]
    長田直樹, 宇野泰広
    日本遺伝学会大会 2011年09月 口頭発表(一般)
  • Compensatory evolution between mitochondrial and nuclear genomes: evidence from primate respiratory chain complex genes  [通常講演]
    Naoki Osada
    SMBE2011 2011年07月 口頭発表(招待・特別)
  • Compensatory Evolution between Mitochondrial and Nuclear Genomes: Evidence from Primate Respiratory Chain Complex Genes  [通常講演]
    Naoki Osada
    Seminar at National Taiwan University 2011年07月 口頭発表(招待・特別)
  • 霊長類の中のヒト:ゲノム多様性の種間比較  [通常講演]
    長田直樹
    遺伝研共同研究集会:ヒト形質のゲノム発掘による新しい進化人類学の創成 2011年07月 口頭発表(一般)
  • ヒトの遺伝的多様性―進化生物学的視点から  [通常講演]
    長田直樹
    日本赤十字第6回学術講演会 2011年06月 口頭発表(招待・特別)
  • Compensatory Evolution between Mitochondrial and Nuclear Genomes: Evidence from Primate Respiratory Chain Complex Genes  [通常講演]
    Naoki Osada
    Seminar at National Cheng-Kung University 2011年03月 口頭発表(招待・特別)
  • 人類集団における自然淘汰  [通常講演]
    長田直樹
    現生人類の拡散による遺伝子と文化の多様性創出に関する総合的研究 2011年03月 口頭発表(一般)
  • Genetic analysis using multi-locus DNA sequence data for ecology and evolution research  [通常講演]
    長田直樹
    NIG Collaborative Research Meeting: Toward Next Generation Studies of Biodiversity and Bioresources 2010年11月 口頭発表(一般)
  • ヒトの遺伝的多様性とゲノムにかかる自然選択について  [通常講演]
    長田直樹
    遺伝研共同研究集会:個人ゲノム時代におけるヒトゲノムDNA多型研究 2010年11月 口頭発表(一般)
  • ミトコンドリア・核遺伝子間の弱有害補完モデル:霊長類COX遺伝子群の進化を例に  [通常講演]
    長田直樹, 明石裕
    日本遺伝学会大会 2010年08月 口頭発表(一般)
  • マルチローカスデータを用いた進化生態学研究について  [通常講演]
    長田直樹
    日本進化学会大会 2010年08月 口頭発表(一般)
  • Polymorphism, Divergence, and Speciation: Genomic Perspective  [通常講演]
    Naoki Osada
    Seminar at National Cheng-Kung University 2010年03月 口頭発表(招待・特別)
  • 実験用霊長類の種差・個体差について:ゲノム解析の視点から  [通常講演]
    長田直樹
    日本薬学会大会融合型シンポジウム 2010年03月 口頭発表(招待・特別)
  • カニクイザルのトランスクリプトーム解析  [通常講演]
    長田直樹
    国際生物多様性会議:霊長類のゲノム多様性研究 2010年03月 口頭発表(一般)
  • 進化生物学への次世代シークエンサーの応用について  [通常講演]
    長田直樹
    国立遺伝学研究所研究集会:次世代シーケンサーを活用したゲノム多様性の研究 2010年01月 口頭発表(一般)
  • カニクイザルcDNAライブラリーの解析とゲノム統合データベースの開発  [通常講演]
    長田直樹, 平田誠, 田沼玲子, 亀岡洋祐, 高橋一朗, 東濃篤範, 鈴木穣, 菅野純夫, 寺尾恵治, 楠田潤, 橋本雄之
    日本分子生物学会年会 2009年12月 ポスター発表
  • 有害な突然変異とその優性度の推定について:ヒト疾患遺伝子の解析  [通常講演]
    長田直樹
    日本遺伝学会大会 2009年09月 口頭発表(一般)
  • Ecological adaptation and speciation: genomic perspective  [通常講演]
    Naoki Osada
    Eawag CEEB joint workshop: Beyond the gaps among ecology, evolution and biogeochemistry 2009年08月 口頭発表(招待・特別)
  • Analysis of gene duplication and conversion in the Drosophila melanogaster genome.  [通常講演]
    Naoki Osada, Hideki Innan
    JSPS Japan-Germany International Colloquium 2009年03月 口頭発表(招待・特別)
  • Polymorphism, Divergence, and Speciation: Genomic Perspective  [通常講演]
    長田直樹
    国立遺伝学研究所 Biological symposium 2009年03月 口頭発表(招待・特別)
  • カニクイザル骨髄・脾臓・膵臓由来cDNAライブラリーの解析  [通常講演]
    長田直樹, 亀岡洋祐, 平田誠, 田沼玲子, 鈴木穣, 菅野純夫, 高橋一朗
    日本分子生物学会年会 2008年12月 ポスター発表
  • ヒトゲノム中の塩基置換多型と疾患関連遺伝子について  [通常講演]
    長田直樹
    日本人類学会大会 2008年11月 口頭発表(一般)
  • Deleterious Mutations and Human Diseases: Genomic Perspective  [通常講演]
    長田直樹
    日本進化学会大会 2008年08月 口頭発表(一般)
  • ヒト疾患とほぼ中立説  [通常講演]
    長田直樹
    国立遺伝学研究所研究集会:中立進化論の現在 2008年07月 口頭発表(招待・特別)
  • 実験用マカク間における遺伝的分化と交雑についてのゲノム解析  [通常講演]
    長田直樹, 亀岡洋祐, 高橋一朗, 寺尾恵治
    日本霊長類学会大会 2008年07月 口頭発表(一般)
  • Pattern of genetic admixture and differentiation between Macaca fascicularis and M. mulatta genome  [通常講演]
    Naoki Osada, Yosuke Kameoka, Ichiro Takahashi, Keiji Terao
    SMBE2008 2008年06月 口頭発表(一般)
  • Primate speciation: genes and genome  [通常講演]
    Naoki Osada
    Seminar at National Taiwan University 2008年05月 口頭発表(招待・特別)
  • Primate speciation: genes and genome  [通常講演]
    長田直樹
    Seminar at National Cheng-Kung University 2008年05月 口頭発表(招待・特別)
  • カニクイザルcDNAライブラリーコレクションの拡充とその解析  [通常講演]
    長田直樹, 橋本雄之, 楠田潤, 亀岡洋祐, 田沼玲子, 平田誠, 高橋一朗
    日本分子生物学会年会 2007年12月 ポスター発表
  • 突然変異にかかる淘汰圧と遺伝子発現の関係について  [通常講演]
    長田直樹
    北海道大学バイオインフォマティクスセミナー 2007年10月 口頭発表(招待・特別)
  • ヒトゲノム中での遺伝子発現パターンと淘汰圧との関係について  [通常講演]
    長田直樹
    日本遺伝学会大会 2007年09月 口頭発表(一般)
  • 遺伝子配列と発現パターンから見た霊長類進化  [通常講演]
    長田直樹
    京都大学霊長類研究所共同利用プログラム/京都大学グローバルCOEプログラム:霊長類ゲノムと脳・感覚研究の最前線 2007年07月 口頭発表(招待・特別)
  • カニクイザル由来cDNAデータベースの構築,アカゲザルとの比較解析  [通常講演]
    長田直樹, 橋本雄之, 平田誠, 田沼玲子, 亀岡洋祐, 楠田潤, 寺尾恵治, 高橋一朗
    日本霊長類学会大会 2007年07月 口頭発表(一般)
  • 高等霊長類でのTMEM30C遺伝子転写の進化  [通常講演]
    長田直樹
    日本進化学会大会 2006年08月 ポスター発表
  • Collection and analysis of primate disease-related homologs  [通常講演]
    Naoki Osada, Reiko Tanuma, Makoto Hirata, Ichirou Takahashi, Yousuke Kameoka, Katsuyuki Hashimoto, Jun Kusuda
    20th International congress of biochemistry and molecular biology and 11th FAOBMB congress 2006年06月 ポスター発表
  • Divergence between human and macaque beyond the protein evolution  [通常講演]
    Naoki Osada, Katsuyuki Hashimoto, Reiko Tanuma, Makoto Hirata, Jun Kusuda
    Human Genome Meeting 2006 2006年05月 口頭発表(一般)
  • カニクイザルcDNAの解析とデータベース構築  [通常講演]
    長田直樹, 平田誠, 田沼玲子, 高橋一朗, 亀岡洋祐, 橋本雄之, 楠田潤
    日本分子生物学会年会 2005年12月 ポスター発表
  • カニクイザルcDNAデータベースの紹介と応用: ミトコンドリア蛋白で起こった正の淘汰  [通常講演]
    長田直樹
    日本遺伝学会大会 2005年09月 口頭発表(一般)
  • ゲノムレベルでわかる霊長類進化  [通常講演]
    長田直樹
    遺伝研生命情報センターCIBセミナー 2005年06月 口頭発表(招待・特別)
  • Cynomolgus monkey cDNA libraries: Rate and Pattern of 5’UTR evolution in primates  [通常講演]
    Naoki Osada, Makoto Hirata, Reiko Tanuma, Jun Kusuda, Katsuyuki Hashimoto
    Human Genome Meeting 2005 2005年04月 ポスター発表
  • Rate and pattern of 5’ UTR evolution: comparative analysis between human and cynomolgus monkey  [通常講演]
    Naoki Osada, Makoto Hirata, Jun Kusuda, Reiko Tanuma, Katsuyuki Hashimoto
    International Workshop on Encoding Information in DNA Sequences 2005年02月 ポスター発表
  • Gene expression of Drosophila melanogaster head with sexual isolation - cis-associated difference and pattern of sex, virginity and genotype  [通常講演]
    長田直樹, Kohn Michael, Greenberg Anthony, Shapiro Joshua, Wu Chung-I
    日本分子生物学会年会 2004年12月 ポスター発表
  • Testing the mode of speciation with genomic data  [通常講演]
    Naoki Osada, Chung-I Wu
    Keystone symposia, Natural variation and quantitative genetics in model organism 2004年03月 ポスター発表
  • カニクイザル脳cDNAを利用したヒトゲノム配列からのヒト新規遺伝子予測  [通常講演]
    長田直樹長田直樹, 肥田宗友, 楠田潤, 田沼玲子, 平田誠, 平井百樹, 橋本雄之
    2002年12月 口頭発表(一般)
  • Identification of human homologs for novel cynomolgus monkey cDNAs  [通常講演]
    Naoki Osada
    Gordon Research Conference: GENOMICS & STRUCTURAL/EVOLUTIONARY BIOINFORMATICS 2002年08月 ポスター発表
  • カニクイザル完全長cDNAの分離ーヒトゲノム配列での新規ヒト遺伝子同定および既知ヒト遺伝子との配列比較  [通常講演]
    長田直樹
    哺乳動物遺伝学研究会 2002年06月 口頭発表(一般)
  • カニクイザル脳由来完全長cDNAライブラリーからの新規遺伝子の探索及び解析  [通常講演]
    長田直樹, 肥田宗友, 楠田潤, 田沼玲子, 伊関可奈子, 平田誠, 平井百樹, 数藤由美子, 橋本雄之
    日本人類学会大会 2001年08月 口頭発表(一般)
  • カニクイザル脳由来完全長cDNAライブラリーの解析と新規遺伝子の探索  [通常講演]
    長田直樹, 肥田宗友, 楠田潤, 田沼玲子, 伊関可奈子, 平田誠, 平井百樹, 数藤由美子, 橋本雄之
    日本分子生物学会年会 2000年11月 ポスター発表
  • CpGアイランドを指標にしたマウス脳由来新規完全長cDNAクローンの分離  [通常講演]
    田直樹, 楠田潤, 田沼玲子, 伊藤亜紀子, 平田誠, 平井百樹, 橋本雄之
    日本分子生物学会年会 1999年11月 ポスター発表
  • ヒト第11番染色体末端領域におけるDNA複製タイミングの解析  [通常講演]
    長田直樹, 笠井文生, 伊関可奈子, 楠田潤, 橋本雄之
    日本分子生物学会年会 1998年11月 ポスター発表
  • 染色体DNA複製タイミングのヒトと近縁霊長類における比較-FISH法による解析  [通常講演]
    長田直樹, 笠井文生, 寺尾恵治, 森祐介, 早坂郁夫
    日本人類学会大会 1998年09月 ポスター発表
  • FISH法を利用したDNA複製タイミングの解析  [通常講演]
    長田直樹, 平井百樹
    日本人類学会大会 1997年11月 ポスター発表
  • Population Genetics of Non-human Primates: How Are We Diverse?  [通常講演]
    Naoki Osada
    International Primatological Society Congress 口頭発表(一般)
  • 進化生物学への次世代シークエンサーの応用について  [通常講演]
    長田直樹
    国立遺伝学研究所研究集会:次世代シーケンサーを活用したゲノム多様性の研究 口頭発表(一般)

その他活動・業績

  • ソフトウェア紹介1:FastQC
    長田直樹 Yaponesian 1 (はる) 20 -21 2019年05月 [査読無し][招待有り]
  • ヤポネシア人の歴史の解明が医学にもたらすもの
    長田直樹 実験医学 37 926 -936 2019年04月 [査読無し][通常論文]
  • ソフトウェア紹介はじまります
    長田直樹 Yaponesian 0 (0) 27 -28 2019年03月 [査読無し][通常論文]
  • 研究計画B03班の紹介
    長田直樹 Yaponesian 0 (0) 16 -17 2019年03月 [査読無し][通常論文]
  • 古代ゲノムの解析手法(情報編)
    長田直樹 細胞工学 34 1092 -1095 2015年11月 [査読無し][招待有り]
  • Naoki Osada Genes and Genetic Systems 90 121 -122 2015年10月 [査読無し][通常論文]
  • 長田直樹 実験医学Webコラム 2015年08月 [査読無し][招待有り]
  • 長田直樹 北海道大学大学院情報科学研究科ネットジャーナル 40 2015年06月 [査読無し][通常論文]
  • 進化学者に聞く!学生からの10の質問
    長田直樹 日本進化学会ニュース 15 (2) 6 -7 2014年 [査読無し][通常論文]
  • 有害な変異と偶然の効果―中立説とほぼ中立説
    長田直樹 遺伝 (5) 322 -326 2013年05月 [査読無し][招待有り]
  • 東濃篤徳, 坂手龍一, 亀岡洋祐, 高橋一朗, 平田誠, 田沼玲子, 増井徹, 保富康宏, 長田直樹 霊長類研究 28 (Supplement) S.22 2012年07月01日 [査読無し][通常論文]
  • 峯田克彦, 松本知高, 長田直樹, 荒木仁志 日本分子生物学会年会プログラム・要旨集(Web) 35th 1P-0013 (WEB ONLY) 2012年 [査読無し][通常論文]
  • 東濃篤徳, 長田直樹, 坂手龍一, 平田誠, 亀岡洋祐, 保富康弘, 高橋一朗 生化学 ROMBUNNO.1P-0709 2010年 [査読無し][通常論文]
  • JCRB遺伝子バンク: 疾患研究と創薬にむけた遺伝子バンク
    長田直樹, 高橋一朗 細胞工学 26 1307 -1308 2007年 [査読無し][招待有り]
  • 第24回日本分子生物学会年会 The 24th Annual Meeting of the Molecular Biology Society of Japan
    長田直樹, 山下順範, 川崎勝己 バイオサイエンスとインダストリー = Bioscience & industry 60 41 -42 2001年 [査読無し][通常論文]
  • 第23回日本分子生物学会年会 The 23th Annual Meeting of the Molecular Biology Society of Japan
    和地正明, 長田直樹, 山下康治 バイオサイエンスとインダストリー = Bioscience & industry 59 40 -41 2000年 [査読無し][通常論文]

受賞

  • 2019年07月 日本学術振興会 特別研究員等審査会専門委員(書面担当)の表彰
     
    受賞者: 長田直樹
  • 2014年09月 日本遺伝学会 日本遺伝学会奨励賞
     ゲノム情報と進化理論の統合による進化機構の解明 
    受賞者: 長田直樹
  • 2007年10月 日本遺伝学会 ベストペーパー賞
     On the correlation between gene expression pattern and selection intensity in the human genome 
    受賞者: 長田直樹

共同研究・競争的資金等の研究課題

  • ヤポネシア人の人口推定を中心とした巨大データ解析
    文部科学省:新学術領域(研究領域提案型)
    研究期間 : 2018年06月 
    代表者 : 長田直樹
  • ゲノム配列を核としたヤポネシア人の起源と成立の解明
    文部科学省:新学術領域(研究領域提案型)
    研究期間 : 2018年06月 
    代表者 : 斎藤成也
  • 文部科学省:科学研究費補助金(基盤研究(C))
    研究期間 : 2014年04月 -2016年03月 
    代表者 : 長田直樹
  • 霊長類ゲノムをモデルとした塩基配列進化の総合的研究
    文部科学省:科学研究費補助金(基盤研究(A))
    研究期間 : 2014年04月 -2016年03月 
    代表者 : 斎藤成也
  • 文部科学省:科学研究費補助金(若手研究(A))
    研究期間 : 2010年 -2013年 
    代表者 : 長田直樹
  • 文部科学省:新学術領域研究
    研究期間 : 2011年04月 
    代表者 : 高橋 文
  • 動物資源の安定供給に向けた繁殖および品質管理技術の高度化に関する研究
    厚生労働省:生物資源研究事業
    研究期間 : 2007年05月 -2010年03月 
    代表者 : 寺尾恵治
  • 文部科学省:科学研究費補助金(基盤研究(C))
    研究期間 : 2007年 -2008年 
    代表者 : 野見山尚之, 瀬戸山千秋, 長田直樹
     
    ケモカインファミリー遺伝子は進化速度が特に早い. そのメンバーであるカニクイザル特異的CXCL1L遺伝子は, mRNAは発現するにもかかわらず, タンパク質はほとんど合成しない. その翻訳抑制機構を解析し, ケモカイン遺伝子進化との関係において考察した.
  • 文部科学省:科学研究費補助金(若手研究(B))
    研究期間 : 2007年 -2008年 
    代表者 : 長田直樹
     
    感染症などの医学研究、創薬などの薬学研究において、哺乳類実験動物、特に霊長類はヒトと遺伝的に非常に近く、重要な位置を占める.ところが、医薬学の実験にサル類の遺伝的多様性がどのような影響を及ぼすかは全くの未知数である.また、これらの実験用霊長類のなかにどれだけの種間・種内の遺伝的多様性があるのかもはっきりとはわかっていないのが現状である.これらを明らかにするため、マカク属の中でも実験用霊長類としてメジャーなアカゲザルとカニクイザルの個体より得られたDNAの多型解析を行った.その結果、1)カニクイザルの遺伝的多様性は現生人類よりも4-5倍高い値を示す、2)カニクイザルとアカゲザルでは、種がわかれた後に遺伝子交流があったかもしれない、3)薬剤代謝にかかわる遺伝子のいくつかは種間の遺伝子での分化度が非常に高い、ということが示された.

教育活動情報

主要な担当授業

  • 情報生物学特論
    開講年度 : 2018年
    課程区分 : 修士課程
    開講学部 : 情報科学研究科
    キーワード : バイオインフォマティクス、遺伝子とタンパク質、分子進化、遺伝子発現情報、生物学データベース
  • バイオエンジニアリング特論
    開講年度 : 2018年
    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
  • 大学院共通授業科目(一般科目):複合領域
    開講年度 : 2018年
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
  • 情報生物学特論
    開講年度 : 2018年
    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 : バイオインフォマティクス、遺伝子とタンパク質、分子進化、遺伝子発現情報、生物学データベース
  • バイオエンジニアリング特論
    開講年度 : 2018年
    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
  • 生命情報解析学
    開講年度 : 2018年
    課程区分 : 学士課程
    開講学部 : 工学部
    キーワード : 遺伝子,ゲノム,DNA,タンパク質,進化,データベース
  • 一般教育演習(フレッシュマンセミナー)
    開講年度 : 2018年
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : 遺伝子診断、個別化医療、遺伝子治療、犯罪捜査、DNA鑑定、遺伝子組換え、ゲノム編集、クローン、デザイナーベイビー、人工生命、古代DNA
  • 生体情報工学演習Ⅱ
    開講年度 : 2018年
    課程区分 : 学士課程
    開講学部 : 工学部
    キーワード : 数値計算法,シミュレーション,統計と検定,データベース,情報検索

大学運営

委員歴

  • 2016年01月 - 現在   日本進化学会   評議員
  • 2019年01月 - 2020年12月   日本遺伝学会   評議員
  • 2018年08月 - 2019年08月   第21回日本進化学会大会   大会準備委員長
  • 2017年07月 - 2019年06月   日本学術振興会   特別研究員等審査会専門委員,卓越研究員候補者選考委員会書面審査員及び国際事業委員会書面審査員・書面評価員
  • 2018年06月 - 2019年03月   原子力規制庁   「染色体線量評価手法の標準化に向けた画像解析技術に係る検討会」委員
  • 2019年02月 - 2019年02月   文部科学省   科研費専門委員会委員
  • 2017年01月 - 2018年12月   日本遺伝学会   評議員
  • 2015年10月 - 2018年10月   先端科学シンポジウム(FoS)シンポジウム事業委員会   プラニンググループメンバー(PGM)
  • 2018年08月 - 2018年08月   日本進化学会   設立時理事
  • 2016年01月 - 2018年08月   日本進化学会   渉外幹事(国内)
  • 2017年 - 2017年   バイオインフォマティクス学会   2017運営委員
  • 2014年01月 - 2015年12月   日本進化学会   庶務幹事
  • 2015年10月 - 2015年10月   第12回日独先端科学シンポジウム(JGFoS)   研究参加者
  • 2011年07月 - 2015年07月   日本霊長類学会   自然保護幹事
  • 2011年 - 2011年   国際分子進化学会(SMBE2011)   Program Committee
  • 2010年 - 2010年   国際霊長類学会会議(IPS2010)   Scientific Committee


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