Takashi Gojobori

Publications of Takashi Gojobori

• A new database (GCD) on genome composition for eukaryote and prokaryote genome sequences and their initial analyses.

  Authors: Kirill Kryukov, Kenta Sumiyama, Kazuho Ikeo, Takashi Gojobori, Naruya Saitou

  Genome biology and evolution. 03/2012;

  Eukaryote genomes contain many non-coding regions and they are quite complex. To understand these complexities, we constructed a database, GCD (Genome Composition Database), for the whole genomeEukaryote genomes contain many non-coding regions and they are quite complex. To understand these complexities, we constructed a database, GCD (Genome Composition Database), for the whole genome composition statistics for 101 eukaryote genome data, as well as more than 1,000 prokaryote genomes. Frequencies of all possible 1-10 oligonucleotides were counted for each genome, and these observed values were compared with expected values computed under observed oligonucleotide frequencies of length 1 to 4. Deviations from expected values were much larger for eukaryotes than prokaryotes, except for fungal genomes. Mammalian genomes showed the largest deviation among animals. The results of comparison are available online at: http://esper.lab.nig.ac.jp/genome-composition-database/

• A prioritization analysis of disease association by data-mining of functional annotation of human genes.

  Authors: Takayuki Taniya, Susumu Tanaka, Yumi Yamaguchi-Kabata, Hideki Hanaoka, Chisato Yamasaki, Harutoshi Maekawa, Roberto A Barrero, Boris Lenhard, Milton W Datta, Mary Shimoyama, Roger Bumgarner, Ranajit Chakraborty, Ian Hopkinson, Libin Jia, Winston Hide, Charles Auffray, Shinsei Minoshima, Tadashi Imanishi, Takashi Gojobori

  Genomics. 01/2012; 99(1):1-9.

  Complex diseases result from contributions of multiple genes that act in concert through pathways. Here we present a method to prioritize novel candidates of disease-susceptibility genes depending onComplex diseases result from contributions of multiple genes that act in concert through pathways. Here we present a method to prioritize novel candidates of disease-susceptibility genes depending on the biological similarities to the known disease-related genes. The extent of disease-susceptibility of a gene is prioritized by analyzing seven features of human genes captured in H-InvDB. Taking rheumatoid arthritis (RA) and prostate cancer (PC) as two examples, we evaluated the efficiency of our method. Highly scored genes obtained included TNFSF12 and OSM as candidate disease genes for RA and PC, respectively. Subsequent characterization of these genes based upon an extensive literature survey reinforced the validity of these highly scored genes as possible disease-susceptibility genes. Our approach, Prioritization ANalysis of Disease Association (PANDA), is an efficient and cost-effective method to narrow down a large set of genes into smaller subsets that are most likely to be involved in the disease pathogenesis.

• The DNA Data Bank of Japan launches a new resource, the DDBJ Omics Archive of functional genomics experiments.

  Authors: Yuichi Kodama, Jun Mashima, Eli Kaminuma, Takashi Gojobori, Osamu Ogasawara, Toshihisa Takagi, Kousaku Okubo, Yasukazu Nakamura

  Nucleic acids research. 11/2011; 40(Database issue):D38-42.

  The DNA Data Bank of Japan (DDBJ; http://www.ddbj.nig.ac.jp) maintains and provides archival, retrieval and analytical resources for biological information. The central DDBJ resource consists ofThe DNA Data Bank of Japan (DDBJ; http://www.ddbj.nig.ac.jp) maintains and provides archival, retrieval and analytical resources for biological information. The central DDBJ resource consists of public, open-access nucleotide sequence databases including raw sequence reads, assembly information and functional annotation. Database content is exchanged with EBI and NCBI within the framework of the International Nucleotide Sequence Database Collaboration (INSDC). In 2011, DDBJ launched two new resources: the 'DDBJ Omics Archive' (DOR; http://trace.ddbj.nig.ac.jp/dor) and BioProject (http://trace.ddbj.nig.ac.jp/bioproject). DOR is an archival database of functional genomics data generated by microarray and highly parallel new generation sequencers. Data are exchanged between the ArrayExpress at EBI and DOR in the common MAGE-TAB format. BioProject provides an organizational framework to access metadata about research projects and the data from the projects that are deposited into different databases. In this article, we describe major changes and improvements introduced to the DDBJ services, and the launch of two new resources: DOR and BioProject.

• Multiple plastids collected by the dinoflagellate Dinophysis mitra through kleptoplastidy.

  Authors: Goh Nishitani, Satoshi Nagai, Shiho Hayakawa, Yuki Kosaka, Kiyonari Sakurada, Takashi Kamiyama, Takashi Gojobori

  Applied and environmental microbiology. 11/2011; 78(3):813-21.

  Kleptoplastidy is the retention of plastids obtained from ingested algal prey, which may remain temporarily functional and be used for photosynthesis by the predator. We showed that the marineKleptoplastidy is the retention of plastids obtained from ingested algal prey, which may remain temporarily functional and be used for photosynthesis by the predator. We showed that the marine dinoflagellate Dinophysis mitra has great kleptoplastid diversity. We obtained 308 plastid rbcL sequences by gene cloning from 14 D. mitra cells and 102 operational taxonomic units (OTUs). Most sequences were new in the genetic database and positioned within Haptophyceae (227 sequences [73.7%], 80 OTUs [78.4%]), particularly within the genus Chrysochromulina. Others were closely related to Prasinophyceae (16 sequences [5.2%], 5 OTUs [4.9%]), Dictyochophyceae (14 sequences [4.5%], 5 OTUs [4.9%]), Pelagophyceae (14 sequences [4.5%], 1 OTU [1.0%]), Bolidophyceae (3 sequences [1.0%], 1 OTU [1.0%]), and Bacillariophyceae (1 sequence [0.3%], 1 OTU [1.0%]); however, 33 sequences (10.8%) as 9 OTUs (8.8%) were not closely clustered with any particular group. Only six sequences were identical to those of Chrysochromulina simplex, Chrysochromulina hirta, Chrysochromulina sp. TKB8936, Micromonas pusilla NEPCC29, Micromonas pusilla CCMP491, and an unidentified diatom. Thus, we detected >100 different plastid sequences from 14 D. mitra cells, strongly suggesting kleptoplastidy and the need for mixotrophic prey such as Laboea, Tontonia, and Strombidium-like ciliates, which retain numerous symbiotic plastids from different origins, for propagation and plastid sequestration.

• Evolutionary patterns of recently emerged animal duplogs.

  Authors: Kiyoshi Ezawa, Kazuho Ikeo, Takashi Gojobori, Naruya Saitou

  Genome biology and evolution. 08/2011; 3:1119-35.

  Duplogs, or intraspecies paralogs, constitute the important portion of eukaryote genomes and serve as a major source of functional innovation. We conducted detailed analyses of recently emergedDuplogs, or intraspecies paralogs, constitute the important portion of eukaryote genomes and serve as a major source of functional innovation. We conducted detailed analyses of recently emerged animal duplogs. Genome data of three vertebrate species (Homo sapiens, Mus musculus, and Danio rerio), Caenorhabditis elegans, and two Drosophila species (Drosophila melanogaster and D. pseudoobscura) were used. Duplication events were divided into six age-groups according to the synonymous distance (dS) up to 0.6. Duplogs were classified into four equal-sized classes on physical distances and into three classes on relative orientations. We observed the following shared characteristics among intrachromosomal multiexon duplogs: 1) inverted duplogs account for 20-50%, and about a half of the physically most distant 25%; 2) except for C. elegans, the composition of physical distances, that of relative orientations, and the proportion of inverted duplogs in each physical distance category are more or less uniform; 3) except for C. elegans, the characteristics of the youngest (dS < 0.01) duplogs are similar to the overall characteristics of the entire set. These results suggest that intrachromosomal duplogs with fairly long physical distances were generated at once, rather than resulting from tandem duplications and subsequent genomic rearrangements. This is different from the three well-known modes of gene duplication: tandem duplication, retrotransposition, and genome duplication. We termed this new mode as "drift" duplication. The drift duplication has been producing duplicate copies at paces comparable with tandem duplications since the common ancestor of vertebrates, and it may have already operated in the common ancestor of bilateral animals.

• Gene dosage imbalance of human chromosome 21 in mouse embryonic stem cells differentiating to neurons.

  Authors: Chi Chiu Wang, Yasuhiro Kazuki, Mitsuo Oshimura, Kazuho Ikeo, Takashi Gojobori

  Gene. 08/2011; 481(2):93-101.

  Gene dosage imbalance is the central working hypothesis in understanding cognitive impairment and learning difficulty in Down syndrome. A mouse embryonic stem cell line containing single humanGene dosage imbalance is the central working hypothesis in understanding cognitive impairment and learning difficulty in Down syndrome. A mouse embryonic stem cell line containing single human chromosome 21 was used to study genomic and transcriptomic implications of autosomal imbalance during early neurogenesis. In this study bioinformatic analysis in the differentiating aneuploid neurons showed 53.6% primary dosage, 25% dosage compensation, and 21.4% reverse dosage effects on trisomic genes, revealing locus-specific secondary dosage effects on disomic genes and its specific trans-acting networks for neural attenuation, degeneration and apoptosis. The obtained results supported the significant gene dosage effects of autosomal imbalance on early neural development, suggesting novel molecular regulations for neurodevelopmental abnormalities in Down syndrome.

• Systems medicine and integrated care to combat chronic noncommunicable diseases.

  Authors: Jean Bousquet, Josep M Anto, Peter J Sterk, Ian M Adcock, Kian Fan Chung, Josep Roca, Alvar Agusti, Chris Brightling, Anne Cambon-Thomsen, Alfredo Cesario [......] Peter Wellstead, Olaf Wolkenhauer, Emiel Wouters, Rudi Balling, Anthony J Brookes, Dominique Charron, Christophe Pison, Zhu Chen, Leroy Hood, Charles Auffray

  Genome medicine. 07/2011; 3(7):43.

  We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic andWe propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

• Evolutionary conserved microRNAs are ubiquitously expressed compared to tick-specific miRNAs in the cattle tick Rhipicephalus (Boophilus) microplus.

  Authors: Roberto A Barrero, Gabriel Keeble-Gagnère, Bing Zhang, Paula Moolhuijzen, Kazuho Ikeo, Yoshio Tateno, Takashi Gojobori, Felix D Guerrero, Ala Lew-Tabor, Matthew Bellgard

  BMC genomics. 06/2011; 12:328.

  MicroRNAs (miRNAs) are small non-coding RNAs that act as regulators of gene expression in eukaryotes modulating a large diversity of biological processes. The discovery of miRNAs has provided newMicroRNAs (miRNAs) are small non-coding RNAs that act as regulators of gene expression in eukaryotes modulating a large diversity of biological processes. The discovery of miRNAs has provided new opportunities to understand the biology of a number of species. The cattle tick, Rhipicephalus (Boophilus) microplus, causes significant economic losses in cattle production worldwide and this drives us to further understand their biology so that effective control measures can be developed. To be able to provide new insights into the biology of cattle ticks and to expand the repertoire of tick miRNAs we utilized Illumina technology to sequence the small RNA transcriptomes derived from various life stages and selected organs of R. microplus. To discover and profile cattle tick miRNAs we employed two complementary approaches, one aiming to find evolutionary conserved miRNAs and another focused on the discovery of novel cattle-tick specific miRNAs. We found 51 evolutionary conserved R. microplus miRNA loci, with 36 of these previously found in the tick Ixodes scapularis. The majority of the R. microplus miRNAs are perfectly conserved throughout evolution with 11, 5 and 15 of these conserved since the Nephrozoan (640 MYA), Protostomian (620MYA) and Arthropoda (540 MYA) ancestor, respectively. We then employed a de novo computational screening for novel tick miRNAs using the draft genome of I. scapularis and genomic contigs of R. microplus as templates. This identified 36 novel R. microplus miRNA loci of which 12 were conserved in I. scapularis. Overall we found 87 R. microplus miRNA loci, of these 15 showed the expression of both miRNA and miRNA* sequences. R. microplus miRNAs showed a variety of expression profiles, with the evolutionary-conserved miRNAs mainly expressed in all life stages at various levels, while the expression of novel tick-specific miRNAs was mostly limited to particular life stages and/or tick organs. Anciently acquired miRNAs in the R. microplus lineage not only tend to accumulate the least amount of nucleotide substitutions as compared to those recently acquired miRNAs, but also show ubiquitous expression profiles through out tick life stages and organs contrasting with the restricted expression profiles of novel tick-specific miRNAs.

• Binary classification of protein molecules into intrinsically disordered and ordered segments.

  Authors: Satoshi Fukuchi, Kazuo Hosoda, Keiichi Homma, Takashi Gojobori, Ken Nishikawa

  BMC structural biology. 06/2011; 11:29.

  Although structural domains in proteins (SDs) are important, half of the regions in the human proteome are currently left with no SD assignments. These unassigned regions consist not only of novelAlthough structural domains in proteins (SDs) are important, half of the regions in the human proteome are currently left with no SD assignments. These unassigned regions consist not only of novel SDs, but also of intrinsically disordered (ID) regions since proteins, especially those in eukaryotes, generally contain a significant fraction of ID regions. As ID regions can be inferred from amino acid sequences, a method that combines SD and ID region assignments can determine the fractions of SDs and ID regions in any proteome. In contrast to other available ID prediction programs that merely identify likely ID regions, the DICHOT system we previously developed classifies the entire protein sequence into SDs and ID regions. Application of DICHOT to the human proteome revealed that residue-wise ID regions constitute 35%, SDs with similarity to PDB structures comprise 52%, while SDs with no similarity to PDB structures account for the remaining 13%. The last group consists of novel structural domains, termed cryptic domains, which serve as good targets of structural genomics. The DICHOT method applied to the proteomes of other model organisms indicated that eukaryotes generally have high ID contents, while prokaryotes do not. In human proteins, ID contents differ among subcellular localizations: nuclear proteins had the highest residue-wise ID fraction (47%), while mitochondrial proteins exhibited the lowest (13%). Phosphorylation and O-linked glycosylation sites were found to be located preferentially in ID regions. As O-linked glycans are attached to residues in the extracellular regions of proteins, the modification is likely to protect the ID regions from proteolytic cleavage in the extracellular environment. Alternative splicing events tend to occur more frequently in ID regions. We interpret this as evidence that natural selection is operating at the protein level in alternative splicing. We classified entire regions of proteins into the two categories, SDs and ID regions and thereby obtained various kinds of complete genome-wide statistics. The results of the present study are important basic information for understanding protein structural architectures and have been made publicly available at http://spock.genes.nig.ac.jp/~genome/DICHOT.

• Towards BioDBcore: a community-defined information specification for biological databases.

  Authors: Pascale Gaudet, Amos Bairoch, Dawn Field, Susanna-Assunta Sansone, Chris F. Taylor, Teresa K. Attwood, Alex Bateman, Judith A. Blake, Carol J. Bult, J. Michael Cherry [......] Lorna Richardson, Philippe Rocca-Serra, Paul N. Schofield, Damian Smedley, Christopher Southan, Tin Wee Tan, Tatiana A. Tatusova, Patricia L. Whetzel, Owen White, Chisato Yamasaki

  Nucleic Acids Research. 01/2011; 39:7-10.

• Towards BioDBcore: a community-defined information specification for biological databases.

  Authors: Pascale Gaudet, Amos Bairoch, Dawn Field, Susanna-Assunta Sansone, Chris Taylor, Teresa K Attwood, Alex Bateman, Judith A Blake, Carol J Bult, J Michael Cherry [......] Lorna Richardson, Philippe Rocca-Serra, Paul N Schofield, Damian Smedley, Christopher Southan, Tin Wee Tan, Tatiana Tatusova, Patricia L Whetzel, Owen White, Chisato Yamasaki

  Nucleic acids research. 01/2011; 39(Database issue):D7-10.

  The present article proposes the adoption of a community-defined, uniform, generic description of the core attributes of biological databases, BioDBCore. The goals of these attributes are to provideThe present article proposes the adoption of a community-defined, uniform, generic description of the core attributes of biological databases, BioDBCore. The goals of these attributes are to provide a general overview of the database landscape, to encourage consistency and interoperability between resources and to promote the use of semantic and syntactic standards. BioDBCore will make it easier for users to evaluate the scope and relevance of available resources. This new resource will increase the collective impact of the information present in biological databases.

• DDBJ progress report.

  Authors: Eli Kaminuma, Takehide Kosuge, Yuichi Kodama, Hideo Aono, Jun Mashima, Takashi Gojobori, Hideaki Sugawara, Osamu Ogasawara, Toshihisa Takagi, Kousaku Okubo, Yasukazu Nakamura

  Nucleic acids research. 11/2010; 39(Database issue):D22-7.

  The DNA Data Bank of Japan (DDBJ, http://www.ddbj.nig.ac.jp) provides a nucleotide sequence archive database and accompanying database tools for sequence submission, entry retrieval and annotationThe DNA Data Bank of Japan (DDBJ, http://www.ddbj.nig.ac.jp) provides a nucleotide sequence archive database and accompanying database tools for sequence submission, entry retrieval and annotation analysis. The DDBJ collected and released 3,637,446 entries/2,272,231,889 bases between July 2009 and June 2010. A highlight of the released data was archive datasets from next-generation sequencing reads of Japanese rice cultivar, Koshihikari submitted by the National Institute of Agrobiological Sciences. In this period, we started a new archive for quantitative genomics data, the DDBJ Omics aRchive (DOR). The DOR stores quantitative data both from the microarray and high-throughput new sequencing platforms. Moreover, we improved the content of the DDBJ patent sequence, released a new submission tool of the DDBJ Sequence Read Archive (DRA) which archives massive raw sequencing reads, and enhanced a cloud computing-based analytical system from sequencing reads, the DDBJ Read Annotation Pipeline. In this article, we describe these new functions of the DDBJ databases and support tools.

• Nematogalectin, a nematocyst protein with GlyXY and galectin domains, demonstrates nematocyte-specific alternative splicing in Hydra.

  Authors: Jung Shan Hwang, Yasuharu Takaku, Tsuyoshi Momose, Patrizia Adamczyk, Suat Özbek, Kazuho Ikeo, Konstantin Khalturin, Georg Hemmrich, Thomas C G Bosch, Thomas W Holstein, Charles N David, Takashi Gojobori

  Proceedings of the National Academy of Sciences of the United States of America. 10/2010; 107(43):18539-44.

  Taxonomically restricted genes or lineage-specific genes contribute to morphological diversification in metazoans and provide unique functions for particular taxa in adapting to specificTaxonomically restricted genes or lineage-specific genes contribute to morphological diversification in metazoans and provide unique functions for particular taxa in adapting to specific environments. To understand how such genes arise and participate in morphological evolution, we have investigated a gene called nematogalectin in Hydra, which has a structural role in the formation of nematocysts, stinging organelles that are unique to the phylum Cnidaria. Nematogalectin is a 28-kDa protein with an N-terminal GlyXY domain (glycine followed by two hydrophobic amino acids), which can form a collagen triple helix, followed by a galactose-binding lectin domain. Alternative splicing of the nematogalectin transcript allows the gene to encode two proteins, nematogalectin A and nematogalectin B. We demonstrate that expression of nematogalectin A and B is mutually exclusive in different nematocyst types: Desmonemes express nematogalectin B, whereas stenoteles and isorhizas express nematogalectin B early in differentiation, followed by nematogalectin A. Like Hydra, the marine hydrozoan Clytia also has two nematogalectin transcripts, which are expressed in different nematocyte types. By comparison, anthozoans have only one nematogalectin gene. Gene phylogeny indicates that tandem duplication of nematogalectin B exons gave rise to nematogalectin A before the divergence of Anthozoa and Medusozoa and that nematogalectin A was subsequently lost in Anthozoa. The emergence of nematogalectin A may have played a role in the morphological diversification of nematocysts in the medusozoan lineage.

• Evolutionary pattern of gene homogenization between primate-specific paralogs after human and macaque speciation using the 4-2-4 method.

  Authors: Kiyoshi Ezawa, Kazuho Ikeo, Takashi Gojobori, Naruya Saitou

  Molecular biology and evolution. 09/2010; 27(9):2152-71.

  Homogenization of duplicated genes is an important factor for gene family evolution. In the previous study, we developed a method, named 4-2-4 here, to detect partial homogenization with highHomogenization of duplicated genes is an important factor for gene family evolution. In the previous study, we developed a method, named 4-2-4 here, to detect partial homogenization with high sensitivity and high specificity using quartets. A quartet is a set of four genes generated by a duplication event and the subsequent speciation of two closely related species. We searched the human and macaque genomes and found 430 nonredundant quartets, which correspond to primate-specific paralogs. The prevalence of homogenization in these quartets was 10.0% (43/430), which was ca. one-third of that (29.8% = 206/691) in the rodent-specific nonredundant quartets obtained through comparison of mouse and rat genomes. Part of this difference comes from the fact that primate paralogs tend to be more remotely located to each other than rodent paralogs, and the remainder may be explained by the inherent difference in the neutral evolutionary rate between the primate and rodent lineages. A statistical analysis taking account of the effects of false negatives uncovered negative correlations between sequence divergence and homogenization prevalence both in primates and rodents. Further statistical analyses controlling for false-negative rates and sequence divergences revealed two characteristics shared by the primate and rodent paralogs; 1) significant negative correlations of the homogenization prevalence with physical distances, and 2) no significant correlation between the prevalence and relative transcriptional orientations. Patterns of the homogenization in the genomic alignments of human-macaque quartets indicate that gene conversion, rather than unequal crossing-over, is the major cause of the homogenization.

• A non-sulfated chondroitin stabilizes membrane tubulation in cnidarian organelles.

  Authors: Patrizia Adamczyk, Claudia Zenkert, Prakash G Balasubramanian, Shuhei Yamada, Saori Murakoshi, Kazuyuki Sugahara, Jung Shan Hwang, Takashi Gojobori, Thomas W Holstein, Suat Ozbek

  The Journal of biological chemistry. 08/2010; 285(33):25613-23.

  Membrane tubulation is generally associated with rearrangements of the cytoskeleton and other cytoplasmic factors. Little is known about the contribution of extracellular matrix components to thisMembrane tubulation is generally associated with rearrangements of the cytoskeleton and other cytoplasmic factors. Little is known about the contribution of extracellular matrix components to this process. Here, we demonstrate an essential role of proteoglycans in the tubulation of the cnidarian nematocyst vesicle. The morphogenesis of this extrusive organelle takes place inside a giant post-Golgi vesicle, which topologically represents extracellular space. This process includes the formation of a complex collagenous capsule structure that elongates into a long tubule, which invaginates after its completion. We show that a non-sulfated chondroitin appears as a scaffold in early morphogenesis of all nematocyst types in Hydra and Nematostella. It accompanies the tubulation of the vesicle membrane forming a provisional tubule structure, which after invagination matures by collagen incorporation. Inhibition of chondroitin synthesis by beta-xylosides arrests nematocyst morphogenesis at different stages of tubule outgrowth resulting in retention of tubule material and a depletion of mature capsules in the tentacles of hydra. Our data suggest a conserved role of proteoglycans in the stabilization of a membrane protrusion as an essential step in organelle morphogenesis.

• The transcript repeat element: the human Alu sequence as a component of gene networks influencing cancer.

  Authors: Paula Moolhuijzen, Jerzy K Kulski, David S Dunn, David Schibeci, Roberto Barrero, Takashi Gojobori, Matthew Bellgard

  Functional & integrative genomics. 04/2010;

  A small percentage (3%) of the 1.3 million copies of Alu sequences in the human genome is expressed individually or as part of various gene transcripts with potential regulatory andA small percentage (3%) of the 1.3 million copies of Alu sequences in the human genome is expressed individually or as part of various gene transcripts with potential regulatory and pathophysiological importance. In order to better understand the role of repetitive elements within transcripts, this review focuses on Alu-containing transcripts of normal and cancerous tissue in a transcriptome-wide survey of the H-Invitational human transcript database on 106,825 tissue-derived transcripts expressed at 29,979 loci. The Alu elements in transcripts of cancerous tissues are significantly underrepresented in comparison to those in normal tissues. In this review, we propose a model for Alu-mediated siRNA down-regulation of Alu-containing transcripts in cancer tissues. In cancer or other rapidly dividing tissues, hypomethylation of repeat element regions triggers the expression of transposon elements including Alu, which can potentially form double-stranded RNA molecules for use as templates to generate Alu-derived siRNAs (Alu-siRNAs). The generated Alu-siRNAs target endogenous messenger RNAs harbouring sequence similarity to Alu elements. This model correlates with the observation that there is substantial under-representation of Alu-containing mRNAs in cancer cells. This new perspective of gene regulation in disease conditions can provide a basis for starting to account for changes in complex gene network in cancer.

• The dynamic genome of Hydra.

  Authors: Jarrod A Chapman, Ewen F Kirkness, Oleg Simakov, Steven E Hampson, Therese Mitros, Thomas Weinmaier, Thomas Rattei, Prakash G Balasubramanian, Jon Borman, Dana Busam [......] J Craig Venter, Ulrich Technau, Bert Hobmayer, Thomas C G Bosch, Thomas W Holstein, Toshitaka Fujisawa, Hans R Bode, Charles N David, Daniel S Rokhsar, Robert E Steele

  Nature. 03/2010; 464(7288):592-6.

  The freshwater cnidarian Hydra was first described in 1702 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexualThe freshwater cnidarian Hydra was first described in 1702 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals. Today, Hydra is an important model for studies of axial patterning, stem cell biology and regeneration. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann-Mangold organizer, pluripotency genes and the neuromuscular junction.

• Dynamic evolution of translation initiation mechanisms in prokaryotes.

  Authors: So Nakagawa, Yoshihito Niimura, Kin-ichiro Miura, Takashi Gojobori

  Proceedings of the National Academy of Sciences of the United States of America. 03/2010; 107(14):6382-7.

  It is generally believed that prokaryotic translation is initiated by the interaction between the Shine-Dalgarno (SD) sequence in the 5' UTR of an mRNA and the anti-SD sequence in the 3' end of a 16SIt is generally believed that prokaryotic translation is initiated by the interaction between the Shine-Dalgarno (SD) sequence in the 5' UTR of an mRNA and the anti-SD sequence in the 3' end of a 16S ribosomal RNA. However, there are two exceptional mechanisms, which do not require the SD sequence for translation initiation: one is mediated by a ribosomal protein S1 (RPS1) and the other used leaderless mRNA that lacks its 5' UTR. To understand the evolutionary changes of the mechanisms of translation initiation, we examined how universal the SD sequence is as an effective initiator for translation among prokaryotes. We identified the SD sequence from 277 species (249 eubacteria and 28 archaebacteria). We also devised an SD index that is a proportion of SD-containing genes in which the differences of GC contents are taken into account. We found that the SD indices varied among prokaryotic species, but were similar within each phylum. Although the anti-SD sequence is conserved among species, loss of the SD sequence seems to have occurred multiple times, independently, in different phyla. For those phyla, RPS1-mediated or leaderless mRNA-used mechanisms of translation initiation are considered to be working to a greater extent. Moreover, we also found that some species, such as Cyanobacteria, may acquire new mechanisms of translation initiation. Our findings indicate that, although translation initiation is indispensable for all protein-coding genes in the genome of every species, its mechanisms have dynamically changed during evolution.

• A comprehensive survey of human polymorphisms at conserved splice dinucleotides and its evolutionary relationship with alternative splicing

  Authors: Makoto Shimada, Yosuke Hayakawa, Jun-ichi Takeda, Takashi Gojobori, Tadashi Imanishi

  BMC Evolutionary Biology. 01/2010;

  Abstract Background Alternative splicing (AS) is a key molecular process that endows biological functions with diversity and complexity. Generally, functional redundancy leads to the generation ofAbstract Background Alternative splicing (AS) is a key molecular process that endows biological functions with diversity and complexity. Generally, functional redundancy leads to the generation of new functions through relaxation of selective pressure in evolution, as exemplified by duplicated genes. It is also known that alternatively spliced exons (ASEs) are subject to relaxed selective pressure. Within consensus sequences at the splice junctions, the most conserved sites are dinucleotides at both ends of introns (splice dinucleotides). However, a small number of single nucleotide polymorphisms (SNPs) occur at splice dinucleotides. An intriguing question relating to the evolution of AS diversity is whether mutations at splice dinucleotides are maintained as polymorphisms and produce diversity in splice patterns within the human population. We therefore surveyed validated SNPs in the database dbSNP located at splice dinucleotides of all human genes that are defined by the H-Invitational Database. Results We found 212 validated SNPs at splice dinucleotides (sdSNPs); these were confirmed to be consistent with the GT-AG rule at either allele. Moreover, 53 of them were observed to neighbor ASEs (AE dinucleotides). No significant differences were observed between sdSNPs at AE dinucleotides and those at constitutive exons (CE dinucleotides) in SNP properties including average heterozygosity, SNP density, ratio of predicted alleles consistent with the GT-AG rule, and scores of splice sites formed with the predicted allele. We also found that the proportion of non-conserved exons was higher for exons with sdSNPs than for other exons. Conclusions sdSNPs are found at CE dinucleotides in addition to those at AE dinucleotides, suggesting two possibilities. First, sdSNPs at CE dinucleotides may be robust against sdSNPs because of unknown mechanisms. Second, similar to sdSNPs at AE dinucleotides, those at CE dinucleotides cause differences in AS patterns because of the arbitrariness in the classification of exons into alternative and constitutive type that varies according to the dataset. Taking into account the absence of differences in sdSNP properties between those at AE and CE dinucleotides, the increased proportion of non-conserved exons found in exons flanked by sdSNPs suggests the hypothesis that sdSNPs are maintained at the splice dinucleotides of newly generated exons at which negative selection pressure is relaxed.

• A comprehensive survey of human polymorphisms at conserved splice dinucleotides and its evolutionary relationship with alternative splicing.

  Authors: Makoto K Shimada, Yosuke Hayakawa, Jun-ichi Takeda, Takashi Gojobori, Tadashi Imanishi

  BMC evolutionary biology. 01/2010; 10:122.

  Alternative splicing (AS) is a key molecular process that endows biological functions with diversity and complexity. Generally, functional redundancy leads to the generation of new functions throughAlternative splicing (AS) is a key molecular process that endows biological functions with diversity and complexity. Generally, functional redundancy leads to the generation of new functions through relaxation of selective pressure in evolution, as exemplified by duplicated genes. It is also known that alternatively spliced exons (ASEs) are subject to relaxed selective pressure. Within consensus sequences at the splice junctions, the most conserved sites are dinucleotides at both ends of introns (splice dinucleotides). However, a small number of single nucleotide polymorphisms (SNPs) occur at splice dinucleotides. An intriguing question relating to the evolution of AS diversity is whether mutations at splice dinucleotides are maintained as polymorphisms and produce diversity in splice patterns within the human population. We therefore surveyed validated SNPs in the database dbSNP located at splice dinucleotides of all human genes that are defined by the H-Invitational Database. We found 212 validated SNPs at splice dinucleotides (sdSNPs); these were confirmed to be consistent with the GT-AG rule at either allele. Moreover, 53 of them were observed to neighbor ASEs (AE dinucleotides). No significant differences were observed between sdSNPs at AE dinucleotides and those at constitutive exons (CE dinucleotides) in SNP properties including average heterozygosity, SNP density, ratio of predicted alleles consistent with the GT-AG rule, and scores of splice sites formed with the predicted allele. We also found that the proportion of non-conserved exons was higher for exons with sdSNPs than for other exons. sdSNPs are found at CE dinucleotides in addition to those at AE dinucleotides, suggesting two possibilities. First, sdSNPs at CE dinucleotides may be robust against sdSNPs because of unknown mechanisms. Second, similar to sdSNPs at AE dinucleotides, those at CE dinucleotides cause differences in AS patterns because of the arbitrariness in the classification of exons into alternative and constitutive type that varies according to the dataset. Taking into account the absence of differences in sdSNP properties between those at AE and CE dinucleotides, the increased proportion of non-conserved exons found in exons flanked by sdSNPs suggests the hypothesis that sdSNPs are maintained at the splice dinucleotides of newly generated exons at which negative selection pressure is relaxed.