Search tips
Search criteria 


Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. 1997 March; 17(3): 1469–1475.
PMCID: PMC231872

Methylation of genomes and genes at the invertebrate-vertebrate boundary.


Patterns of DNA methylation in animal genomes are known to vary from an apparent absence of modified bases, via methylation of a minor fraction of the genome, to genome-wide methylation. Representative genomes from 10 invertebrate phyla comprise predominantly nonmethylated DNA and (usually but not always) a minor fraction of methylated DNA. In contrast, all 27 vertebrate genomes that have been examined display genome-wide methylation. Our studies of chordate genomes suggest that the transition from fractional to global methylation occurred close to the origin of vertebrates, as amphioxus has a typically invertebrate methylation pattern whereas primitive vertebrates (hagfish and lamprey) have patterns that are typical of vertebrates. Surprisingly, methylation of genes preceded this transition, as many invertebrate genes have turned out to be heavily methylated. Methylation does not preferentially affect genes whose expression is highly regulated, as several housekeeping genes are found in the heavily methylated fraction whereas several genes expressed in a tissue-specific manner are in the nonmethylated fraction.

Full Text

The Full Text of this article is available as a PDF (755K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. [PubMed]
  • Antequera F, Macleod D, Bird AP. Specific protection of methylated CpGs in mammalian nuclei. Cell. 1989 Aug 11;58(3):509–517. [PubMed]
  • Antequera F, Tamame M, Villanueva JR, Santos T. DNA methylation in the fungi. J Biol Chem. 1984 Jul 10;259(13):8033–8036. [PubMed]
  • Antoine M, Fried M. The organization of the intron-containing human S6 ribosomal protein (rpS6) gene and determination of its location at chromosome 9p21. Hum Mol Genet. 1992 Nov;1(8):565–570. [PubMed]
  • Bestor TH, Tycko B. Creation of genomic methylation patterns. Nat Genet. 1996 Apr;12(4):363–367. [PubMed]
  • Bird A, Taggart M, Frommer M, Miller OJ, Macleod D. A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell. 1985 Jan;40(1):91–99. [PubMed]
  • Bird A, Tweedie S. Transcriptional noise and the evolution of gene number. Philos Trans R Soc Lond B Biol Sci. 1995 Sep 29;349(1329):249–253. [PubMed]
  • Bird AP. Functions for DNA methylation in vertebrates. Cold Spring Harb Symp Quant Biol. 1993;58:281–285. [PubMed]
  • Bird AP. Gene number, noise reduction and biological complexity. Trends Genet. 1995 Mar;11(3):94–100. [PubMed]
  • Bird AP, Taggart MH. Variable patterns of total DNA and rDNA methylation in animals. Nucleic Acids Res. 1980 Apr 11;8(7):1485–1497. [PMC free article] [PubMed]
  • Bird AP, Taggart MH, Smith BA. Methylated and unmethylated DNA compartments in the sea urchin genome. Cell. 1979 Aug;17(4):889–901. [PubMed]
  • Boyes J, Bird A. Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl-CpG binding protein. EMBO J. 1992 Jan;11(1):327–333. [PubMed]
  • Cedar H, Solage A, Glaser G, Razin A. Direct detection of methylated cytosine in DNA by use of the restriction enzyme MspI. Nucleic Acids Res. 1979;6(6):2125–2132. [PMC free article] [PubMed]
  • Chan SJ, Cao QP, Steiner DF. Evolution of the insulin superfamily: cloning of a hybrid insulin/insulin-like growth factor cDNA from amphioxus. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9319–9323. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Cooper DN, Taggart MH, Bird AP. Unmethylated domains in vertebrate DNA. Nucleic Acids Res. 1983 Feb 11;11(3):647–658. [PMC free article] [PubMed]
  • Cross S, Kovarik P, Schmidtke J, Bird A. Non-methylated islands in fish genomes are GC-poor. Nucleic Acids Res. 1991 Apr 11;19(7):1469–1474. [PMC free article] [PubMed]
  • Freedman T, Pukkila PJ. De novo methylation of repeated sequences in Coprinus cinereus. Genetics. 1993 Oct;135(2):357–366. [PubMed]
  • Fronk J, Tank GA, Langmore JP. DNA methylation pattern changes during development of a sea urchin. Biochem J. 1992 May 1;283(Pt 3):751–753. [PubMed]
  • George NC, Killian CE, Wilt FH. Characterization and expression of a gene encoding a 30.6-kDa Strongylocentrotus purpuratus spicule matrix protein. Dev Biol. 1991 Oct;147(2):334–342. [PubMed]
  • Holland LZ, Pace DA, Blink ML, Kene M, Holland ND. Sequence and expression of amphioxus alkali myosin light chain (AmphiMLC-alk) throughout development: implications for vertebrate myogenesis. Dev Biol. 1995 Oct;171(2):665–676. [PubMed]
  • Holland PW, Garcia-Fernàndez J, Williams NA, Sidow A. Gene duplications and the origins of vertebrate development. Dev Suppl. 1994:125–133. [PubMed]
  • Holmquist GP. Evolution of chromosome bands: molecular ecology of noncoding DNA. J Mol Evol. 1989 Jun;28(6):469–486. [PubMed]
  • Mohandas T, Sparkes RS, Shapiro LJ. Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation. Science. 1981 Jan 23;211(4480):393–396. [PubMed]
  • Rae PM, Steele RE. Absence of cytosine methylation at C-C-G-G and G-C-G-C sites in the rDNA coding regions and intervening sequences of Drosophila and the rDNA of other insects. Nucleic Acids Res. 1979 Jul 11;6(9):2987–2995. [PMC free article] [PubMed]
  • Reynaud C, Bruno C, Boullanger P, Grange J, Barbesti S, Niveleau A. Monitoring of urinary excretion of modified nucleosides in cancer patients using a set of six monoclonal antibodies. Cancer Lett. 1992 Jan 31;61(3):255–262. [PubMed]
  • Riggs AD, Pfeifer GP. X-chromosome inactivation and cell memory. Trends Genet. 1992 May;8(5):169–174. [PubMed]
  • Satoh N, Jeffery WR. Chasing tails in ascidians: developmental insights into the origin and evolution of chordates. Trends Genet. 1995 Sep;11(9):354–359. [PubMed]
  • Simoens CR, Gielen J, Van Montagu M, Inzé D. Characterization of highly repetitive sequences of Arabidopsis thaliana. Nucleic Acids Res. 1988 Jul 25;16(14B):6753–6766. [PMC free article] [PubMed]
  • Singer J, Roberts-Ems J, Luthardt FW, Riggs AD. Methylation of DNA in mouse early embryos, teratocarcinoma cells and adult tissues of mouse and rabbit. Nucleic Acids Res. 1979 Dec 20;7(8):2369–2385. [PMC free article] [PubMed]
  • Whittaker PA, McLachlan A, Hardman N. Sequence organisation in nuclear DNA from Physarum polycephalum: methylation of repetitive sequences. Nucleic Acids Res. 1981 Feb 25;9(4):801–814. [PMC free article] [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)