[2B4] ポストゲノムシークエンス時代の進化多様性研究

種別	シンポジウム
提案者	五條堀　孝（遺伝研)
趣旨	２００２年４月にヒトゲノム配列の完全終了宣言がおこなわれる。一方、すでに米国では、ＤＮＡチップによって２５人５０ゲノムの全ゲノム配列決定によるＳＮＰ（Single Nucleotide Polymorphism）の特定が終わり、チンパンジー１個体の全ゲノムのＳＮＰも約１週間程度ですでに同定されている。さらに、どのような生物のゲノム配列決定もわずか１０００ドルでおこなうための技術開発プロジェクトが真剣に議論されている。また、遺伝子の同定やその機能の特定を大規模な確証実験によって遂行する動きも活発化してきている。これらは、明確な目的をもったデータベースの生物学的構築を前提に、「比較ゲノム」と「機能ゲノム」を有機的にとりまぜながら、ゲノム情報にどこまで高次の表現形や形質をmappingできるかという研究パラダイムが確立しつつあることを意味する。たとえば、米英が中心になって準備している「ＥＮＣＯＤＥ」という新規の巨大プロジェクトも、明らかにこのパラダイムの上に設計されている。言い換えれば、この「研究パラダイム」は、ゲノム情報を基盤とする「進化学」そのものであり、「ゲノム進化学」という通常の「ゲノムの進化学」概念を超えるものである。つまり、この研究パラダイムに従えば、ＳＮＰに基づく表現形としての疾病の責任遺伝子の追求から、遺伝子制御や遺伝子相互作用に基づく比較発生過程や種分化の解明まで、生命現象を動的な情報の流れとして時間的・空間的に理解しようとする思想的インセンティブとして一括的に捉えることが可能となる。この思想的なインセンティブこそ、生命現象の統合化理解であり、現代進化学のもつ大きなインセンティブそのものである。このような「研究パラダイム」を明示的に意識して研究をおこない始めた研究者の方々に講演をお願いし、「ポストゲノムシーケンシング時代の進化学」のあり方を議論する。

予定講演者の氏名、所属、タイトル

• "Comparative and functional genomics - evolutionary studies as the backbone of new integrative biology"
  Takashi Gojobori (National Institute of Genetics)

  Under the situation that the human genome sequencing project has been completely finished, the time has changed into the so-called post-genome sequencing era. In the post-genome sequencing, it looks obvious that comparative and functional genomics will become crucial disciplines of immediate interest. For conducting comparative and functional genomics with the maximum efficiency, the philosophical backbone will be required. In particular, an attempt of understanding all levels of biological hierarchy in a unified way will be made by evoking "data-driven science" as well as "working hypothesis oriented-science." If this attempt can be called as "new integrative biology," organismic diversity and evolution should be the backbone of new integrative biology.

• "A new direction of human gene studies: the integrative database of human full-length cDNA clones"
  Roberto Barrero (Japan Biological Information Research Center)

  With the draft sequences of the human, mouse and rat genomes available, the next challenge in the understanding of basic human molecular biology is the difficult task of interpretation of the human genome in terms of various aspects such as structure, function, diversity and evolution of protein-coding genes as well as non-protein coding genes, regulation of gene expression in tissues and states of health, protein-gene and protein-protein interactions. It is also a particular importance to integrate this information in an easily accessible form. The Human Full-Length cDNA Annotation Invitational project (H-Invitational; H-Inv) emerged as an international collaboration project to systematically and functionally validate human genes by analysis of a unique set of high quality full-length cDNA clones by automatic annotation and human curation under unified criteria. We also created a human gene database, H-Invitational Database (H-InvDB), with integrative annotation of biological, structural, functional and evolutionary information for each human gene. The H-Inv DB represents the largest human gene collection that will promote a variety of studies including comparative and functional genomics.

• "Medical science in the post-genome era"
  Yasuyuki Fukumaki (Kyushu University)

  Medical science in the post-genome era is mainly devoted to identification of genetic contributions to human complex traits of medical interest, such as disease susceptibility and drug response, leading to establishment of personalized medicine and preventive medicine. I will present our efforts at hunting the susceptibility loci for schizophrenia, and discuss the prospects. Such complex traits will be elucidated by combination of comparative and functional genomics at not only molecular level but also evolutionary level.

• "Tsukuba BB and other Algorithms for Sequence Motif Discovery: Promise and Limitations"
  Paul Horton (Computational Biology Research Center)

  Sequence motif discovery programs promise to automatically find patterns in DNA or protein sequences by examining patterns in some way to optimize a likelihood ratio scoring function. The reality is that the most commonly used heuristic algorithms: EM, MM, Gibb's sampling, and beam search do not provide any guarantee regarding the quality of the pattern they return relative to the pattern with the highest likelihood ratio present in the input sequences. TsukubaBB is an "exhaustive" method which always returns the pattern with the highest likelihood ratio -- but unfortunately is often too slow. We describe recent efforts to 1. speed up TsukubaBB and 2. empirically quantify the quality of patterns returned by heuristic algorithms.

• "Comparative studies of gene expression for the evolution of a brain"
  Jung Shan Hwang (Japan Science and Technology Corporation)

  Multicellular animals possess various forms of nervous system, it can be as simple as a diffuse nerve net (Cnidaria and Ctenophora) or as complex as a highly organized system consists of brain, spinal cord and peripheral components (mammals). To understand how the nervous system has changed in the course of evolutionary process, we take a comparative approach to study the nervous systems of hydra (Phylum Cnidaria) and planarian (Phylum Platyhelminthes) at gene level. Moreover, despite the anatomical diversity between the central nervous systems of invertebrate and vertebrate, recent molecular studies support that a great deal of conservation lies between the two systems. Here, we examine in situ gene expression patterns in planarian by using a set of orthologous genes which are known to be expressed highly in the brain of mouse embryo. We would therefore be able to study the evolutionary relationship of central nervous systems between the invertebrate and vertebrate.

• "Genetic addiction: a principle of gene symbiosis in a genome"
  Ichizo Kobayashi (Tokyo University)

  Some genes can program growth arrest or death of cells when they get disturbed or lost. By doing so, these genes force their host cells to maintain them. This process of genetic addiction may represent a general strategy by which genes maintain a cohesive symbiotic community in the form of a genome. A genome may take advantage of this form of growth arrest/death for its survival under various stresses --- infection, starvation and DNA damage. Such deaths involving intra-genomic conflicts may have shaped the evolution of genomes and genetic systems.