Genome evolution induced by chromatin structure and DNA methylation

• Project/Area Number: 23241058
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Genome biology
• Research Institution: The University of Tokyo
• Principal Investigator: MORISHITA Shinichi 東京大学, 新領域創成科学研究科, 教授 (90292854)
• Co-Investigator(Kenkyū-buntansha): TAKEDA Hiroyuki 東京大学, 大学院理学系研究科, 教授 (80179647) ; HASHIMOTO Shinichi 金沢大学, 医学系, 特任教授 (00313099)
• Project Period (FY): 2011-05-31 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥38,220,000 (Direct Cost: ¥29,400,000、Indirect Cost: ¥8,820,000); Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000); Fiscal Year 2011: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
• Keywords: DNAメチル化 / 塩基置換 / 進化 / 近交系 / ヒトゲノム / メダカゲノム / ゲノム

Research Abstract

Natural selection and neutral theory of evolution have been crucial to understand genetic variation and evolution. In this study, we have examined whether chromatin structure and DNA methylation might affect genetic variation and evolution. Indeed, we identified an unexpected genome-wide role of the CpG methylation state as a major determinant of proximal natural genetic variation. ~18% of the human genome was within 10 bp of a CpG site; in these regions, the single nucleotide polymorphism rate significantly increased by ~50% (P<E-566) if the neighboring CpG sites are methylated. In two medaka inbred strains, we observed a distinctive ~200-base pair periodic pattern of genetic variation downstream of transcription start sites and its correlation with the chromatin structure. These data exemplify the potential for genetic activity (transcription), DNA methylation, and chromatin structure to contribute to molding the DNA sequence on an evolutionary time scale.

Research Products

• [Journal Article] A simple but powerful heuristic method for accelerating k-means clustering of large-scale data in life science (2014)
  • Author(s): Kazuki Ichikawa and Shinichi Morishita
  • Journal Title: IEEE/ACM Transactions on Computational Biology and Bioinformatics(TCBB) Volume: (印刷中) Issue: 4 Pages: 681-692
  • DOI: 10.1109/tcbb.2014.2306200
  • Peer Reviewed
• [Journal Article] The transcription start site landscape of C. elegans (2013)
  • Author(s): Saito TL, Hashimoto S, Gu SG, Morton JJ, Stadler M, Blumenthal T, Fire A, Morishita S
  • Journal Title: Genome Research Volume: 23(8) Issue: 8 Pages: 1348-61
  • DOI: 10.1101/gr.151571.112
  • Peer Reviewed
• [Journal Article] Segmental duplications in the silkworm genome (2013)
  • Author(s): Zhao Q, Zhu Z, Kasahara M, Morishita S, Zhang Z
  • Journal Title: BMC Genomics Volume: 14(1) Issue: 1 Pages: 521-521
  • DOI: 10.1186/1471-2164-14-521
  • Peer Reviewed
• [Journal Article] Comparing the Human and Fish Genomes (2013)
  • Author(s): Nakatani Y, Qu W, Morishita S
  • Journal Title: In : eLS 2013, John Wiley & Sons Ltd Volume: (電子出版のためページ番号無し)
  • DOI: 10.1002/9780470015902.a0021004.pub2
  • Peer Reviewed
• [Journal Article] Coordinated Changes in DNA Methylation in Antigen-Specific Memory CD4 T Cells (2013)
  • Author(s): Hashimoto S, Ogoshi K, Sasaki A, Abe J, Qu W, Nakatani Y, Ahsan B, Oshima K, Shand FH, Ametani A, Suzuki Y, Kaneko S, Wada T, Hattori M, Sugano S,Morishita S, Matsushima K
  • Journal Title: J Immunol Volume: 190 Issue: 8 Pages: 4076-4091
  • DOI: 10.4049/jimmunol.1202267
  • Peer Reviewed
• [Journal Article] ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish. (2013)
  • Author(s): Ishikawa, T.
  • Journal Title: Mol Biol Cell. Volume: 24(9) Pages: 1387-1395
  • Peer Reviewed
• [Journal Article] Genome-wide genetic variations are highly correlated with proximal DNA methylation patterns (2012)
  • Author(s): Qu W, Hashimoto S, Shimada A, Nakatani Y, Ichikawa K, Saito TL, Ogoshi K, Matsushima K, Suzuki Y, Sugano S, Takeda H, Morishita S.
  • Journal Title: Genome Res Volume: 22 Issue: 8 Pages: 1419-1425
  • DOI: 10.1101/gr.140236.112
  • Peer Reviewed
• [Journal Article] Extremely slow rate of evolution in the HOX cluster revealed by comparison between Tanzanian and Indonesian coelacanths. (2012)
  • Author(s): Higasa K, Nikaido M, Saito TL, Yoshimura J, Suzuki Y, Suzuki H, Nishihara H, Aibara M, Ngatunga BP, Kalombo HW, Sugano S, Morishita S, Okada N.
  • Journal Title: Gene Volume: 505 Issue: 2 Pages: 324-332
  • DOI: 10.1016/j.gene.2012.05.047
  • Peer Reviewed
• [Journal Article] The medaka zic1/zic4 mutant provides molecular insights into teleost caudal fin evolution. (2012)
  • Author(s): Yuuta Moriyama
  • Journal Title: Current Biology Volume: 21 Issue: 7 Pages: 601-607
  • DOI: 10.1016/j.cub.2012.01.063
  • Peer Reviewed
• [Journal Article] Genome-wide profiling of DNA methylation in human cancer cells (2011)
  • Author(s): Katsumi Ogoshi, et al
  • Journal Title: Genomics Volume: 98 Issue: 4 Pages: 280-287
  • DOI: 10.1016/j.ygeno.2011.07.003
  • Peer Reviewed
• [Journal Article] Genome-wide profiling of DNA methylation in human cancer cells (2011)
  • Author(s): Ogoshi K., et al.
  • Journal Title: Genomics Volume: 98 Pages: 280-287
  • Peer Reviewed
• [Journal Article] Genome-wide characterization of transcriptional start sites in humans by integrative transcriptome analysis (2011)
  • Author(s): Yamashita, R., et al.
  • Journal Title: Genome Research Volume: 21 Pages: 775-789
  • Peer Reviewed
• [Presentation] Estimating unmethylated DNA blocks in vertebrates by SMRT Sequencing (2013)
  • Author(s): Suzuki, Y
  • Organizer: Advanced in Genome Biology and Technology, 2013
  • Place of Presentation: Florida, USA
• [Presentation] Epigenetic Inheritance and Regulation in Whole Genome Duplication (2013)
  • Author(s): Qu, W.
  • Organizer: Advanced in Genome Biology and Technology, 2013
  • Place of Presentation: Florida, USA
• [Remarks] 効率的クラスタリングアルゴリズム k-means Clustering for Pearson correlation
  • URL: http://mlab.cb.k.u-tokyo.ac.jp/?ichikawa/boostKCP/
• [Remarks] 線虫の転写開始点データベース WormTSS:The Primary Transcriptome of C. elegans
  • URL: http://wormtss.utgenome.org/browser
• [Remarks] メダカゲノムのDNA メチル化情報データベース Medaka Methylome Browser
  • URL: http://utgenome.org/methylome/
• [Remarks] k-means Clustering for Pearson correlation
  • URL: http://mlab.cb.k.u-tokyo.ac.jp/~ichikawa/boostKCP/
• [Remarks] WormTSS:The Primary Transcriptome of C. elegans
  • URL: http://wormtss.utgenome.org/browser/
• [Remarks] Medaka Methylome Browser
  • URL: http://utgenome.org/methylome/