2001 Fiscal Year Annual Research Report

胃炎胃潰瘍胃ガンの病因であるピロリ菌等の多型形成にはたす制限修飾酵素遺伝子の役割

Research Project

Project/Area Number	12470034
Research Institution	The University of Tokyo
Principal Investigator	小林一三東京大学, 医科学研究所, 助教授 (30126057)
Co-Investigator(Kenkyū-buntansha)	内山郁夫岡崎国立共同研究機構, 基礎生物学, 助手 (90243089)
Keywords	病原細菌 / 細菌ゲノム / ゲノム多型 / ゲノム不安定性 / ゲノム進化 / ゲノム比較 / 病原性 / 毒素
Research Abstract	A..ゲノム配列の比較と解析。 (A-1)ゲノム比較ツールの開発。以下の過程で、近縁ゲノム比較ツールCGATを改良した。 (A-2)ピロリ菌、パイロコッカス。二株を比較して、ゲノム多型への制限修飾遺伝子の関与を示唆した。 (A-3)ブドウ球菌Staphylococcus。薬剤耐性黄色ブドウ球菌S.aureusのMRSA, VRSA2株のゲノム配列を比較し、中規模多型をカタログ化し、形成機構を推測した。毒素原性を担う「動く遺伝子」塊に乗っている制限修飾遺伝子ホモログを解析し、二つの座にまたがる「二つの顔を持つ制限修飾系」を推測した。また、制限修飾遺伝子の毒素遺伝子群の重複と多様化への関与を提唱した。別の種についても、動く遺伝子単位に乗った制限修飾遺伝子を解析した。これら制限修飾遺伝子がこれらの動く遺伝子単位の安定化に関与している可能性を提唱した。これらのゲノム中に遠縁の生物との遺伝子水平伝達の候補を同定した。 (A-4)髄膜炎菌Neisseria。N.meningitidis(髄膜炎菌)の二株、N.gonorhoeae(淋菌)の一株を比較し、制限修飾遺伝子と関連したゲノム多型を検出した。反復配列のゲノム多型をカタログ化した。 B.多型ダイナミクスの実験室での解析。 (B-1)制限修飾遺伝子のゲノム内転移を実証した。 (B-2)染色体上の制限修飾遺伝子の増幅を発見し、構造とダイナミックスを解析した。考察:以上の成果は、制限酵素修飾酵素遺伝子が「利己的な動く遺伝子」であり、病原細菌など細菌ゲノムの多型形成に寄与していることを示唆する。制限修飾遺伝子の存在が脅かされたときにおきる染色体攻撃は、「異変が起きた細胞を排除することによってゲノムを安定維持する」と同時に、「再編ゲノムをおこし」、「そのうち制限修飾遺伝子の発現が回復したものを生き残らせる」効果がある。

Research Products

(23 results)

All Other

All Publications (23 results)

[Publications] Y.Fujitani: "A reaction-diffusion model for interference in meiotic crossing-over"Genetics. (in press).
[Publications] I.Kobayashi: "Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution"Mol.Microbiol.. 40. 932-940 (2001)
[Publications] M.Kuroda: "Whole genome sequencing of meticillin-resistant Staphylococcus aureus"The Lancet. 357. 1225-1240 (2001)
[Publications] H.Handa: "Y. Nakayama, M. Sadykov and I. Kobayashi. Experimental genome evolution : large-scale genome rearrangements associated with resistance to replacement of a chromosomal restriction-modification gene complex"Mol.Microbiol.. 40. 932-940 (2001)
[Publications] A.Chinen: "Comparison between Pyrococcus horikoshii and Pyrococcus abyssi genome sequences suggests association of restriction-modification genes with gross genome polymorphism""Gene. 259. 109-121 (2000)
[Publications] A.Nobusato: "Insertion with long target duplication : A mechanism for restriction-modification-mediated gene mobility suggested from comparison of two complete bacterial genomes"Gene. 259. 99-108 (2000)
[Publications] A.Nobusato: "Diversity of restriction modification gene homologues in Helicobacter pylori"Gene. 259. 89-98 (2000)
[Publications] A.Chinen: "Evolution of sequence recognition by restriction-modification enzymes : selective pressure for specificity decrease"Mol.Biol.Evol.. 17. 1610-1619 (2000)
[Publications] D.A.Arnold: "A novel, 11-nucleotide variant of χ, χ:one of a class of sequences defining the E. coli recombination hotspot, χ"J.Mol.Biol.. 300. 469-479 (2000)
[Publications] N.Handa: "Cellular responses to post-segregational killing by restriction-modification genes"J.Bacteriol.. 182. 2218-2229 (2000)
[Publications] I.Kobayashi: "Sex as a strategy against"non-self"genetic elements"J.Rep.Dev.. 46. s7-s8 (2000)
[Publications] 小林一三: "ゲノム比較:ゲノムつくり換えていた制限酵素修飾酵素遺伝子"蛋白質核酸酵素、臨時増刊号「ゲノムサイエンスの新たなる挑戦」. 46. 2393-2399 (2001)
[Publications] 小林一三: "なぜ微生物実験進化か?"SHINKA. 10. 31-34 (2000)
[Publications] 小林一三: "ゲノムはなぜ変わるのか? 利己的な動く遺伝子たちのコミュニティーとしてのゲノム"科学. 70. 335-345 (2000)
[Publications] K.Nakao: "Genome Informatics 2001"Relation between restriction modification genes and genome rearrangements suggested from genome sequence comparison within Genus Neisseria. 2 (2001)
[Publications] I.Kobayashi: "the Encyclopedia of Life Sciences"DNA double-strand break repair in bacteria (on-line publication). (2001)
[Publications] I.Uchiyama: "Genome Informatics 2000"Universal Academy Press, Tokyo. 3 (2000)
[Publications] A.Chinen: "Genome Informatics 2000"Universal Academy Press, Tokyo. 2 (2000)
[Publications] K.Gerdes: "The Horizontal Gene Pool"Harwood academic publishers gmbh, Amsterdam. 10 (2000)
[Publications] Y.Fujitani: "Computational Molecular Biology"Universal Academy Press Inc., Tokyo. 2 (2000)
[Publications] I.Uchiyama: "Computational Molecular Biology"Universal Academy Press Inc., Tokyo. 2 (2000)
[Publications] I.Kobayashi: "International Collection for Microbiology Teaching and Learning"American Society for Microbiology, Washington DC. (2000)
[Publications] I.Uchiyama: "データベース:http://mbgd.genome.ad.jp"Human Genome Center, Institute of Medical Science, The University of Tokyo. (2000)

2001 Fiscal Year Annual Research Report

胃炎胃潰瘍胃ガンの病因であるピロリ菌等の多型形成にはたす制限修飾酵素遺伝子の役割

Principal Investigator

小林 一三 東京大学, 医科学研究所, 助教授 (30126057)

Research Products

[Publications] Y.Fujitani: "A reaction-diffusion model for interference in meiotic crossing-over"Genetics. (in press).

[Publications] I.Kobayashi: "Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution"Mol.Microbiol.. 40. 932-940 (2001)

[Publications] M.Kuroda: "Whole genome sequencing of meticillin-resistant Staphylococcus aureus"The Lancet. 357. 1225-1240 (2001)

[Publications] H.Handa: "Y. Nakayama, M. Sadykov and I. Kobayashi. Experimental genome evolution : large-scale genome rearrangements associated with resistance to replacement of a chromosomal restriction-modification gene complex"Mol.Microbiol.. 40. 932-940 (2001)

[Publications] A.Chinen: "Comparison between Pyrococcus horikoshii and Pyrococcus abyssi genome sequences suggests association of restriction-modification genes with gross genome polymorphism""Gene. 259. 109-121 (2000)

[Publications] A.Nobusato: "Insertion with long target duplication : A mechanism for restriction-modification-mediated gene mobility suggested from comparison of two complete bacterial genomes"Gene. 259. 99-108 (2000)

[Publications] A.Nobusato: "Diversity of restriction modification gene homologues in Helicobacter pylori"Gene. 259. 89-98 (2000)

[Publications] A.Chinen: "Evolution of sequence recognition by restriction-modification enzymes : selective pressure for specificity decrease"Mol.Biol.Evol.. 17. 1610-1619 (2000)

[Publications] D.A.Arnold: "A novel, 11-nucleotide variant of χ, χ:one of a class of sequences defining the E. coli recombination hotspot, χ"J.Mol.Biol.. 300. 469-479 (2000)

[Publications] N.Handa: "Cellular responses to post-segregational killing by restriction-modification genes"J.Bacteriol.. 182. 2218-2229 (2000)

[Publications] I.Kobayashi: "Sex as a strategy against"non-self"genetic elements"J.Rep.Dev.. 46. s7-s8 (2000)

[Publications] 小林一三: "ゲノム比較:ゲノムつくり換えていた制限酵素修飾酵素遺伝子"蛋白質核酸酵素、臨時増刊号「ゲノムサイエンスの新たなる挑戦」. 46. 2393-2399 (2001)

[Publications] 小林一三: "なぜ微生物実験進化か?"SHINKA. 10. 31-34 (2000)

[Publications] 小林一三: "ゲノムはなぜ変わるのか? 利己的な動く遺伝子たちのコミュニティーとしてのゲノム"科学. 70. 335-345 (2000)

[Publications] K.Nakao: "Genome Informatics 2001"Relation between restriction modification genes and genome rearrangements suggested from genome sequence comparison within Genus Neisseria. 2 (2001)

[Publications] I.Kobayashi: "the Encyclopedia of Life Sciences"DNA double-strand break repair in bacteria (on-line publication). (2001)

[Publications] I.Uchiyama: "Genome Informatics 2000"Universal Academy Press, Tokyo. 3 (2000)

[Publications] A.Chinen: "Genome Informatics 2000"Universal Academy Press, Tokyo. 2 (2000)

[Publications] K.Gerdes: "The Horizontal Gene Pool"Harwood academic publishers gmbh, Amsterdam. 10 (2000)

[Publications] Y.Fujitani: "Computational Molecular Biology"Universal Academy Press Inc., Tokyo. 2 (2000)

[Publications] I.Uchiyama: "Computational Molecular Biology"Universal Academy Press Inc., Tokyo. 2 (2000)

[Publications] I.Kobayashi: "International Collection for Microbiology Teaching and Learning"American Society for Microbiology, Washington DC. (2000)

[Publications] I.Uchiyama: "データベース:http://mbgd.genome.ad.jp"Human Genome Center, Institute of Medical Science, The University of Tokyo. (2000)

小林一三東京大学, 医科学研究所, 助教授 (30126057)