Who We Are
地球上のすべての生命は起源を同じくしており、遺伝情報の比較から生物の進化・多様性プロセスを明らかにできる。次世代ショートリードシーケンサだけでなく、第三世代ロングリードシーケンサなども活用しつつ、機械学習などの新しい解析技術を取り入れ多様な研究を展開。
Introduction
ゲノム比較 異なる特徴を有する近縁種や、似た特徴を有する遠縁種のゲノム比較から、その特徴の基盤となる遺伝メカニズムを解析。
遺伝子発現比較 様々な状況の遺伝子発現ネットワークを比較から生物の様々な機能メカニズムを解析。
進化プロセス解析 オーソログ遺伝子を種分岐順に調べ、遺伝子の新機能の獲得プロセスを解析。
集団内多様性解析 生物集団、細胞集団などの塩基多型や発現プロファイル多型を表現型と合わせて解析することで、表現型に関係した遺伝子を同定。
遺伝子発現比較 様々な状況の遺伝子発現ネットワークを比較から生物の様々な機能メカニズムを解析。
進化プロセス解析 オーソログ遺伝子を種分岐順に調べ、遺伝子の新機能の獲得プロセスを解析。
集団内多様性解析 生物集団、細胞集団などの塩基多型や発現プロファイル多型を表現型と合わせて解析することで、表現型に関係した遺伝子を同定。
Researches
頭足類を用いた脳神経系研究
頭足類は5億年以上前の先カンブリア紀に脊椎動物とは分岐し、独立に高度なカメラ眼や脳神経系を発達させた。脳神経系比較モデルとして、原始的なオウムガイやラボで飼育できるヒメイカなどを用いて比較ゲノム・トランスクリプトーム解析から脳神経系進化の鍵を探索。一つの遺伝子から複数の転写産物を産み出す選択的スプライシングが関与していることを発見。
生物由来の接着剤
生物由来の接着剤の研究。普通の接着剤と異なり、接着・剥離が簡単で、水中で使用でき、無毒で生分解性があるため、医療用接着剤として有望。医療用接着剤は世界で一兆円規模の成長市場だが、現在普及している医療接着剤は主として化学合成由来で生体への安全性などが不安視されている。
細胞の多様性
ひとつの個体の内部であっても細胞には多様性があり、様々な役割を果たしている。一細胞レベルで遺伝子発現多様性を解析することが可能なシングルセルトランスクリプトームを用いて、病気になる前の未病シグナルの検出を目指す。分子予防医学の最新展開で、Quality of Lifeの向上が可能に。
共生システムの進化
生命の最大の躍進のひとつである葉緑体の獲得。現代においても一部原生動物が緑藻を細胞内共生させており、植物が10億年前に経験した進化イベントを現在進行形で経験中。ミドリゾウリムシとクロレラの細胞内共生システム解明のために、共生・非共生クロレラの比較ゲノムやホスト-シンビオント・トランスクリプトーム研究を行い共生のスイッチを探る。将来的には人工的な細胞内共生を目指し共生デザイン研究も視野に。研究の過程で進化プロセスが不明な巨大ウイルスの挿入痕跡も発見。
ハビタットDNA
消化管内容物や生息域のプランクトンをDNAシーケンサで調べて生き物が何を食べてどのような生活スタイルを持っているのか観察するハビタットDNA分析、環境中の水をDNAシーケンサにかけるだけでその水域の生物叢がわかる環境DNA分析。次世代シーケンサが可能にする新たな生態・環境調査手法を開発。5年以上食事を取らずに生活したダイオウグソクムシの消化管の中身は？飼育環境下でエサを食べないヒメイカの幼生は自然界で何を食べている？などを明らかに。
解析手法の開発
Selected Works
Comparative genome and transcriptome analysis of diatom, Skeletonema costatum, reveals evolution of genes for harmful algal bloom
Atsushi Ogura, Yuki Akizuki, Hiroaki Imoda, Katsuhiko Mineta, Takashi Gojobori and Satoshi Nagai
BMC Genomics (2018) 19:765
https://doi.org/10.1186/s12864-018-5144-5
Although the camera eye of the octopus is very similar to that of humans, phylogenetic and embryological analyses have suggested that their camera eyes have been acquired independently. It has been known as a typical example of convergent evolution. To study the molecular basis of convergent evolution of camera eyes, we conducted a comparative analysis of gene expression in octopus and human camera eyes. We sequenced 16,432 ESTs of the octopus eye, leading to 1052 nonredundant genes that have matches in the protein database. Comparing these 1052 genes with 13,303 already-known ESTs of the human eye, 729 (69.3%) genes were commonly expressed between the human and octopus eyes. On the contrary, when we compared octopus eye ESTs with human connective tissue ESTs, the expression similarity was quite low. To trace the evolutionary changes that are potentially responsible for camera eye formation, we also compared octopus-eye ESTs with the completed genome sequences of other organisms. We found that 1019 out of the 1052 genes had already existed at the common ancestor of bilateria, and 875 genes were conserved between humans and octopuses. It suggests that a larger number of conserved genes and their similar gene expression may be responsible for the convergent evolution of the camera eye.
De novo assembly of middle-sized genome using MinION and Illumina sequencers
Ryuhei Minei, Ryo Hoshina and Atsushi Ogura
BMC Genomics (2018) 19:700
https://doi.org/10.1186/s12864-018-5067-1
Background: The plastid acquisition by secondary endosymbiosis is a driving force for the algal evolution, and the comparative genomics was required to examine the genomic change of symbiont. Therefore, we established a pipeline of a de novo assembly of middle-sized genomes at a low cost and with high quality using long and short reads.
Results: We sequenced symbiotic algae Chlorella variabilis using Oxfofrd Nanopore MinION as the long-read sequencer and Illumina HiSeq 4000 as the short-read sequencer and then assembled the genomes under various conditions. Subsequently, we evaluated these assemblies by the gene model quality and RNA-seq mapping rate. We found that long-read only assembly could not be suitable for the comparative genomics studies, but with short reads, we could obtain the acceptable assembly. On the basis of this result, we established the pipeline of de novo assembly for middle-sized algal genome using MinION.
Conclusions: The genomic change during the early stages of plastid acquisition can now be revealed by sequencing and comparing many algal genomes. Moreover, this pipeline offers a solution for the assembly of various middle-sized eukaryotic genomes with high-quality and ease.
Molecular Evidence for Convergence and Parallelism in Evolution of Complex Brains of Cephalopod Molluscs: Insights from Visual Systems
M. A. Yoshida, A. Ogura, K. Ikeo, S. Shigeno, T. Moritaki, G. C. Winters, A. B. Kohn and L. L. Moroz
Integrative and Comparative Biology, volume 55, number 6, pp. 1070–1083
http://dx.doi.org/doi:10.1093/icb/icv049
Although the camera eye of the octopus is very similar to that of humans, phylogenetic and embryological analyses have suggested that their camera eyes have been acquired independently. It has been known as a typical example of convergent evolution. To study the molecular basis of convergent evolution of camera eyes, we conducted a comparative analysis of gene expression in octopus and human camera eyes. We sequenced 16,432 ESTs of the octopus eye, leading to 1052 nonredundant genes that have matches in the protein database. Comparing these 1052 genes with 13,303 already-known ESTs of the human eye, 729 (69.3%) genes were commonly expressed between the human and octopus eyes. On the contrary, when we compared octopus eye ESTs with human connective tissue ESTs, the expression similarity was quite low. To trace the evolutionary changes that are potentially responsible for camera eye formation, we also compared octopus-eye ESTs with the completed genome sequences of other organisms. We found that 1019 out of the 1052 genes had already existed at the common ancestor of bilateria, and 875 genes were conserved between humans and octopuses. It suggests that a larger number of conserved genes and their similar gene expression may be responsible for the convergent evolution of the camera eye.
Distinct evolutionary rate in the eye field transcription factors found by estimation of ancestral protein structure
Ai Kamijyo, Kei Yura, Atsushi Ogura
Gene 555 (2015) 73–79
http://dx.doi.org/10.1016/j.gene.2014.10.003
Although the camera eye of the octopus is very similar to that of humans, phylogenetic and embryological analyses have suggested that their camera eyes have been acquired independently. It has been known as a typical example of convergent evolution. To study the molecular basis of convergent evolution of camera eyes, we conducted a comparative analysis of gene expression in octopus and human camera eyes. We sequenced 16,432 ESTs of the octopus eye, leading to 1052 nonredundant genes that have matches in the protein database. Comparing these 1052 genes with 13,303 already-known ESTs of the human eye, 729 (69.3%) genes were commonly expressed between the human and octopus eyes. On the contrary, when we compared octopus eye ESTs with human connective tissue ESTs, the expression similarity was quite low. To trace the evolutionary changes that are potentially responsible for camera eye formation, we also compared octopus-eye ESTs with the completed genome sequences of other organisms. We found that 1019 out of the 1052 genes had already existed at the common ancestor of bilateria, and 875 genes were conserved between humans and octopuses. It suggests that a larger number of conserved genes and their similar gene expression may be responsible for the convergent evolution of the camera eye.
Cephalopod eye evolution was modulated by the acquisition of Pax-6 splicing variants
Masa-aki Yoshida, Kei Yura& Atsushi Ogura
SCIENTIFIC REPORTS | 4 : 4256
https://doi.org/10.1038/srep04256
Previous studies have reported that the developmental processes of vertebrate eyes are controlled by four Pax-6 splicing variants, each modulating different downstream genes, whereas those of insect eyes are controlled by duplicated Pax-6 genes. Cephalopods belong to the Protostomes but possess a camera-type eye similar to those in vertebrates. We examined Pax-6 variations in the squid and found five types of Pax-6 splicing variants but no duplication of the Pax-6 gene. In the five splicing variants, the splicing patterns were produced by the combination of two additional exons to the ortholog and one jettisoned exon containing most of the Homeobox domain (HD). These five variants show spatio-temporal patterns of gene expression during development in the squid. Our study suggests that cephalopods acquired Pax-6 splicing variants independent of those in vertebrates and that these variants were similarly utilized in the development of the squid eye.
Sensing deep extreme environments: the receptor cell types, brain centers, and multi-layer neural packaging of hydrothermal vent endemic worms
Shuichi Shigeno, Atsushi Ogura, Tsukasa Mori, Haruhiko Toyohara, Takao Yoshida, Shinji Tsuchida and Katsunori Fujikura
Frontiers in Zoology 2014, 11:82
http://www.frontiersinzoology.com/content/11/1/82
Introduction: Deep-sea alvinellid worm species endemic to hydrothermal vents, such as Alvinella and Paralvinella, are considered to be among the most thermotolerant animals known with their adaptability to toxic heavy metals, and tolerance of highly reductive and oxidative stressful environments. Despite the number of recent studies focused on their overall transcriptomic, proteomic, and metabolic stabilities, little is known regarding their sensory receptor cells and electrically active neuro-processing centers, and how these can tolerate and function in such harsh conditions.
Results: We examined the extra- and intracellular organizations of the epidermal ciliated sensory cells and their higher centers in the central nervous system through immunocytochemical, ultrastructural, and neurotracing analyses. We observed that these cells were rich in mitochondria and possessed many electron-dense granules, and identified specialized glial cells and serial myelin-like repeats in the head sensory systems of Paralvinella hessleri. Additionally, we identified the major epidermal sensory pathways, in which a pair of distinct mushroom bodies-like or small interneuron clusters was observed. These sensory learning and memory systems are commonly found in insects and annelids, but the alvinellid inputs are unlikely derived from the sensory ciliary cells of the dorsal head regions.
Conclusions: Our evidence provides insight into the cellular and system-wide adaptive structure used to sense, process, and combat the deep-sea hydrothermal vent environment. The alvinellid sensory cells exhibit characteristics of annelid ciliary types, and among the most unique features were the head sensory inputs and structure of the neural cell bodies of the brain, which were surrounded by multiple membranes. We speculated that such enhanced protection is required for the production of normal electrical signals, and to avoid the breakdown of the membrane surrounding metabolically fragile neurons from oxidative stress. Such pivotal acquisition is not broadly found in the all body parts, suggesting the head sensory inputs are specific, and these heterogenetic protection mechanisms may be present in alvinellid worms.
Loss of the six3/6 controlling pathways might have resulted in pinhole-eye evolution in Nautilus
Atsushi Ogur, Masa-aki Yoshida, Takeya Moritaki, Yuki Okuda, Jun Sese, Kentaro K. Shimizu, Konstantinos Sousounis & Panagiotis A. Tsonis
SCIENTIFIC REPORTS | 3 : 1432
https://doi.org/10.1038/srep01432
Coleoid cephalopods have an elaborate camera eye whereas nautiloids have primitive pinhole eye without lens and cornea. The Nautilus pinhole eye provides a unique example to explore the module of lens formation and its evolutionary mechanism. Here, we conducted an RNA-seq study of developing eyes of Nautilus and pygmy squid. First, we found that evolutionary distances from the common ancestor to Nautilus or squid are almost the same. Although most upstream eye development controlling genes were expressed in both species, six3/6 that are required for lens formation in vertebrates was not expressed in Nautilus. Furthermore, many downstream target genes of six3/6 including crystallin genes and other lens protein related genes were not expressed in Nautilus. As six3/6 and its controlling pathways are widely conserved among molluscs other than Nautilus, the present data suggest that deregulation of the six3/6 pathway led to the pinhole eye evolution in Nautilus.
Transcriptome Analysis of Nautilus and Pygmy Squid Developing Eye Provides Insights in Lens and Eye Evolution
Konstantinos Sousounis, Atsushi Ogura, Panagiotis A. Tsonis
PLoS ONE 8(10): e78054
https://doi.org/10.1371/journal.pone.0078054
Coleoid cephalopods like squids have a camera-type eye similar to vertebrates. On the other hand, Nautilus (Nautiloids) has a pinhole eye that lacks lens and cornea. Since pygmy squid and Nautilus are closely related species they are excellent model organisms to study eye evolution. Having being able to collect Nautilus embryos, we employed next-generation RNA sequencing using Nautilus and pygmy squid developing eyes. Their transcriptomes were compared and analyzed. Enrichment analysis of Gene Ontology revealed that contigs related to nucleic acid binding were largely up-regulated in squid, while the ones related to metabolic processes and extracellular matrix-related genes were up-regulated in Nautilus. These differences are most likely correlated with the complexity of tissue organization in these species. Moreover, when the analysis focused on the eye-related contigs several interesting patterns emerged. First, contigs from both species related to eye tissue differentiation and morphogenesis as well as to cilia showed best hits with their Human counterparts, while contigs related to rabdomeric photoreceptors showed the best hit with their Drosophila counterparts. This bolsters the idea that eye morphogenesis genes have been generally conserved in evolution, and compliments other studies showing that genes involved in photoreceptor differentiation clearly follow the diversification of invertebrate (rabdomeric) and vertebrate (ciliated) photoreceptors. Interestingly some contigs showed as good a hit with Drosophila and Human homologues in Nautilus and squid samples. One of them, capt/CAP1, is known to be preferentially expressed in Drosophila developing eye and in vertebrate lens. Importantly our analysis also provided evidence of gene duplication and diversification of their function in both species. One of these genes is the Neurofibromatosis 1 (NF1/ Nf1), which in mice has been implicated in lens formation, suggesting a hitherto unsuspected role in the evolution of the lens in molluscs.
Cephalopod genomics: A plan of strategies and organization
The Cephalopod Sequencing Consortium
Standards in Genomic Sciences (2012) 7:175-188
https://doi.org/10.4056/sigs.3136559
The Cephalopod Sequencing Consortium (CephSeq Consortium) was established at a NESCent Catalysis Group Meeting, “Paths to Cephalopod Genomics- Strategies, Choices, Organization,” held in Durham, North Carolina, USA on May 24-27, 2012. Twenty-eight participants representing nine countries (Austria, Australia, China, Denmark, France, Italy, Japan, Spain and the USA) met to address the pressing need for genome sequencing of cephalopod mollusks. This group, drawn from cephalopod biologists, neuroscientists, developmental and evolutionary biologists, materials scientists, bioinformaticians and researchers active in sequencing, assembling and annotating genomes, agreed on a set of cephalopod species of particular importance for initial sequencing and developed strategies and an organization (CephSeq Consortium) to promote this sequencing. The conclusions and recommendations of this meeting are described in this white paper.
Genome structure analysis of molluscs revealed whole genome duplication and lineage specific repeat variation
Masa-aki Yoshida, Yukiko Ishikura, Takeya Moritaki, Eiichi Shoguchi, Kentaro K. Shimizu, Jun Sese, Atsushi Ogura
Gene 483 (2011) 63–71
https://doi.org/10.1016/j.gene.2011.05.027
Comparative genome structure analysis allows us to identify novel genes, repetitive sequences and gene duplications. To explore lineage-specific genomic changes of the molluscs that is good model for development of nervous system in invertebrate, we conducted comparative genome structure analyses of three molluscs, pygmy squid, nautilus and scallops using partial genome shotgun sequencing. Most effective elements on the genome structural changes are repetitive elements (REs) causing expansion of genome size and whole genome duplication producing large amount of novel functional genes. Therefore, we investigated variation and proportion of REs and whole genome duplication. We, first, identified variations of REs in the three molluscan genomes by homology-based and de novo RE detection. Proportion of REs were 9.2%, 4.0%, and 3.8% in the pygmy squid, nautilus and scallop, respectively. We, then, estimated genome size of the species as 2.1, 4.2 and 1.8 Gb, respectively, with 2× coverage frequency and DNA sequencing theory. We also performed a gene duplication assay based on coding genes, and found that large-scale duplication events occurred after divergence from the limpet Lottia, an out-group of the three molluscan species. Comparison of all the results suggested that RE expansion did not relate to the increase in genome size of nautilus. Despite close relationships to nautilus, the squid has the largest portion of REs and smaller genome size than nautilus. We also identified lineage-specific RE and gene-family expansions, possibly relate to acquisition of the most complicated eye and brain systems in the three species.
Effective gene collection from the metatranscriptome of marine microorganisms
Atsushi Ogura, Mengjie Lin, Yuya Shigenobu, Atushi Fujiwara, Kazuho Ikeo, Satoshi Nagai
BMC Genomics 2011, 12(Suppl 3):S15
http://www.biomedcentral.com/1471-2164/12/S3/S15
Background: Metagenomic studies, accelerated by the evolution of sequencing technologies and the rapid development of genomic analysis methods, can reveal genetic diversity and biodiversity in various samples including those of uncultured or unknown species. This approach, however, cannot be used to identify active functional genes under actual environmental conditions. Metatranscriptomics, which is similar in approach to metagenomics except that it utilizes RNA samples, is a powerful tool for the transcriptomic study of environmental samples. Unlike metagenomic studies, metatranscriptomic studies have not been popular to date due to problems with reliability, repeatability, redundancy and cost performance. Here, we propose a normalized metatranscriptomic method that is suitable for the collection of genes from samples as a platform for comparative transcriptomics.
Results: We constructed two libraries, one non-normalized and the other normalized library, from samples of marine microorganisms taken during daylight hours from Hiroshima bay in Japan. We sequenced 0.6M reads for each sample on a Roche GS FLX, and obtained 0.2M genes after quality control and assembly. A comparison of the two libraries showed that the number of unique genes was larger in the normalized library than in the nonnormalized library. Functional analysis of genes revealed that a small number of gene groups, ribosomal RNA genes and chloroplast genes, were dominant in both libraries. Taxonomic distribution analysis of the libraries suggests that Stramenopiles form a major taxon that includes diatoms. The normalization technique thus increases unique genes, functional categories of genes, and taxonomic richness.
Conclusions: Normalization of the marine metatranscriptome could be useful in increasing the number of genes collected, and in reducing redundancies among highly expressed genes. Gene collection through the normalization method was effective in providing a foundation for comparative transcriptomic analysis.
Genetic mechanisms involved in the evolution of the cephalopod camera eye revealed by transcriptomic and developmental studies
Masa-aki Yoshida and Atsushi Ogura
BMC Evolutionary Biology 2011, 11:180
http://www.biomedcentral.com/1471-2148/11/180
Background: Coleoid cephalopods (squids and octopuses) have evolved a camera eye, the structure of which is very similar to that found in vertebrates and which is considered a classic example of convergent evolution. Other molluscs, however, possess mirror, pin-hole, or compound eyes, all of which differ from the camera eye in the degree of complexity of the eye structures and neurons participating in the visual circuit. Therefore, genes expressed in the cephalopod eye after divergence from the common molluscan ancestor could be involved in eye evolution through association with the acquisition of new structural components. To clarify the genetic mechanisms that contributed to the evolution of the cephalopod camera eye, we applied comprehensive transcriptomic analysis and conducted developmental validation of candidate genes involved in coleoid cephalopod eye evolution.
Results: We compared gene expression in the eyes of 6 molluscan (3 cephalopod and 3 non-cephalopod) species and selected 5,707 genes as cephalopod camera eye-specific candidate genes on the basis of homology searches against 3 molluscan species without camera eyes. First, we confirmed the expression of these 5,707 genes in the cephalopod camera eye formation processes by developmental array analysis. Second, using molecular evolutionary (dN/dS) analysis to detect positive selection in the cephalopod lineage, we identified 156 of these genes in which functions appeared to have changed after the divergence of cephalopods from the molluscan ancestor and which contributed to structural and functional diversification. Third, we selected 1,571 genes, expressed in the camera eyes of both cephalopods and vertebrates, which could have independently acquired a function related to eye development at the expression level. Finally, as experimental validation, we identified three functionally novel cephalopod camera eye genes related to optic lobe formation in cephalopods by in situ hybridization analysis of embryonic pygmy squid.
Conclusion: We identified 156 genes positively selected in the cephalopod lineage and 1,571 genes commonly found in the cephalopod and vertebrate camera eyes from the analysis of cephalopod camera eye specificity at the expression level. Experimental validation showed that the cephalopod camera eye-specific candidate genes include those expressed in the outer part of the optic lobes, which unique to coleoid cephalopods. The results of this study suggest that changes in gene expression and in the primary structure of proteins (through positive selection) from those in the common molluscan ancestor could have contributed, at least in part, to cephalopod camera eye acquisition.
In vitro homology search array comprehensively reveals highly conserved genes and their functional characteristics in non-sequenced species
Atsushi OguraEmail author, Masa-aki Yoshida, Mutsumi Fukuzaki and Jun Sese
BMC Genomics201011 (Suppl 4) :S9
https://doi.org/10.1186/1471-2164-11-S4-S9
Comparative Analysis of Gene Expression for Convergent Evolution of Camera Eye Between Octopus and Human
Atsushi Ogura, Kazuho Ikeo, and Takashi Gojobori
Genome Resarch. 2004 Au.14(8):1555-61
http://www.genome.org/cgi/doi/10.1101/gr.2268104
Although the camera eye of the octopus is very similar to that of humans, phylogenetic and embryological analyses have suggested that their camera eyes have been acquired independently. It has been known as a typical example of convergent evolution. To study the molecular basis of convergent evolution of camera eyes, we conducted a comparative analysis of gene expression in octopus and human camera eyes. We sequenced 16,432 ESTs of the octopus eye, leading to 1052 nonredundant genes that have matches in the protein database. Comparing these 1052 genes with 13,303 already-known ESTs of the human eye, 729 (69.3%) genes were commonly expressed between the human and octopus eyes. On the contrary, when we compared octopus eye ESTs with human connective tissue ESTs, the expression similarity was quite low. To trace the evolutionary changes that are potentially responsible for camera eye formation, we also compared octopus-eye ESTs with the completed genome sequences of other organisms. We found that 1019 out of the 1052 genes had already existed at the common ancestor of bilateria, and 875 genes were conserved between humans and octopuses. It suggests that a larger number of conserved genes and their similar gene expression may be responsible for the convergent evolution of the camera eye.
Profile
小倉淳
教授
Education
1998: BSc University of Tokyo
2000: MSc University of Tokyo
2003: PhD. Graduate University for Advanced Studies
Career
2003: Postdoc @National Institute of Genetics
2004-06: Postdoc (JSPS) @Tohoku University
2004-06: Postdoc @Harvard University
2007-08: Asst. Prof. @National Institute of Genetics
2008-12: Asst. Prof. @Ochanomizu University
2012-13: Lecturer @The University of Tokushima
2013-2019: Assoc. Prof. @Nagahama Institute of Bio-Science and Technology
2019-: Prof. @Nagahama Institute of Bio-Science and Technology
Editorial Board
BMC Genomics, Associate Editor
Human Genomics, Editorial Board
Get In Touch
Contact Info
address:
〒526-0829
滋賀県長浜市田村町1266
長浜バイオ大学
tel: 0749-64-8127
email: aogu@whelix.info
twitter: @aogura