Summary
The extent to which CpG dinucleotides were depleted in a large set of angiosperm genes was, on average, very similar to the extent of CpG depletion in total angiosperm genomic DNA and far less than the extent of CpG depletion in vertebrate genes. Gene sequences from Arabidopsis thaliana, a dicotyledonous species with relatively low levels of total 5-methylcytosine, were just as CpG depleted as the angiosperm genes in general. Furthermore, levels of TpG and CpA, the potential deamination mutation products of methylated CpG, were elevated in A. thaliana genes, supporting a high rate of deamination mutation as the cause of the CpG deficiency. Using a method that takes into account the dinucleotide frequencies within each sequence of interest, we calculated the expected frequencies of CpNpG trinucleotides, which are also highly methylated in angiosperm genomes. CpNpG trinucleotides were not extensively enriched or depleted in the angiosperm genes. Two hypotheses could account for our results. Differential depletion of CpG and CpNpG within angiosperm genes and differential depletion of CpG in angiosperm and vertebrate genes could arise from different efficiencies of mismatch repair or from different levels of cytosine methylation in the cell lineages that contribute to germ cells.
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References
Adams RLP, Eason R (1984) Increased G+C content of DNA stabilises methyl CpG dinucleotides. Nucleic Acids Res 12: 5869–5877
Bianchi MW, Viotti A (1988) DNA methylation and tissue-specific transcription of the storage protein genes of maize. Plant Mol Biol 11:203–214
Bird A, Taggart M, Frommer M, Miller OJ, Macleod D (1985) A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell 40:91–99
Bird AP (1980) DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res 8:1499–1504
Bird AP (1986) CpG-rich islands and the function of DNA methylation. Nature 321:209–213
Bonen L, Huh TY, Gray MW (1980) Can partial methylation explain the complex fragment patterns observed when plant mitochondrial DNA is cleaved with restriction endonucleases. FEBS Lett 111:340–346
Boudraa M, Perrin P (1987) CpG and TpA frequencies in the plant system. Nucleic Acids Res 15:5729–5737
Brown TC, Jiricny J (1987) A specific mismatch repair event protects mammalian cells from loss of 5-methylcytosine. Cell 50:945–950
Bulmer M (1986) Neighboring base effects on substitution rates in pseudogenes. Mol Biol Evol 3:322–329
Cedar H, Razin A (1990) DNA methylation and development. Biochim Biophys Acta 1049:1–8
Cooper DN, Gerber-Huber S (1985) DNA methylation and CpG suppression. Cell Differ 17:199–205
Coulondre C, Miller JH, Farabaugh PJ, Gilbert W (1978) Molecular basis of base substitution hotspots in Escherichia coli. Nature 274:775–780
Cowan R (in press) J Appl Probab
Flavell RB (1985) Repeated sequences and genome change. In: Hohn B, Dennis ES (eds) Genetic flux in plants. Springer-Verlag, New York, pp 129–156
Flavell RB, Bennett MD, Smith JB, Smith DB (1974) Genome size and the proportion of repeated nucleotide sequence DNA in plants. Biochem Genet 12:257–269
Gardiner-Garden M, Frommer M (1987) CpG islands in vertebrate genomes. J Mol Biol 196:261–282
Gardiner-Garden M, Frommer M (1992) Significant CpG-rich regions in angiosperm genes. J Mol Evol 34:231–245
Ginsburg M, Snow MHL, McLaren A (1990) Primordial germ cells in the mouse embryo during gastrulation. Development 110:521–528
Graham MW, Doherty JP, Woodcock DM (1990) Efficient construction of plant genomic libraries requires the use of mcr host strains and packaging mixes. Plant Mol Biol Rep 8:18–27
Gruenbaum Y, Naveh-Many T, Cedar H, Razin A (1981a) Sequence specificity of methylation in higher plant DNA. Nature 292:860–862
Gruenbaum Y, Stein R, Cedar H, Razin A (1981b) Methylation of CpG sequences in eukaryotic DNA. FEBS Lett 124:67–71
Hepburn AG, Belanger FC, Mattheis JR (1987) DNA methylation in plants. Dev Genet 8:475–493
Holliday R, Monk M, Pugh JE (1990) DNA methylation and gene regulation. The Royal Society, London
Josse J, Kaiser AD, Kornberg A (1961) Enzymatic synthesis of deoxyribonucleic acid: VIII. Frequencies of nearest neighbor base sequences in deoxyribonucleic acid. J Biol Chem 236: 864–875
Leutwiler LS, Hough-Evans BR, Meyerowitz EM (1984) The DNA of Arabidopsis thaliana. Mol Gen Genet 194:15–23
Martinez-Zapater JM, Estelle MA, Somerville CR (1986) A highly repeated DNA sequence in Arabidopsis thaliana. Mol Gen Genet 204:417–423
Matassi G, Montero LM, Salinas J, Bernardi G (1989) The isochore organization and the compositional distribution of homologous coding sequences in the nuclear genome of plants. Nucleic Acids Res 17:5273–5290
McClelland M (1983) The frequency and distribution of methylatable DNA sequences in leguminous plant protein coding genes. J Mol Evol 19:346–354
McClelland M, Ivarie R (1982) Asymmetrical distribution of CpG in an ‘average’ mammalian gene. Nucleic Acids Res 10: 7865–7877
Naveh-Many T, Cedar H (1982) Topographical distribution of 5-methylcytosine in animal and plant DNA. Mol Cell Biol 2: 758–762
Nelson O (1988) Plant transposable elements. Plenum, Madison WI
Ngernprasirtsiri J, Kobayashi H, Akazawa T (1989) Transcriptional regulation and DNA methylation of nuclear genes for photosynthesis in nongreen plant cells. Proc Natl Acad Sci USA 86:7919–7923
Nick H, Bowen B, Ferl RJ, Gilbert W (1986) Detection of cytosine methylation in the maize alcohol dehydrogenase gene by genomic sequencing. Nature 319:243–246
Nyce J, Liu L, Jones PA (1986) Variable effects of DNA-synthesis inhibitors upon DNA methylation in mammalian cells. Nucleic Acids Res 14:4353–4367
Pruitt RE, Meyerowitz EM (1986) Characterization of the genome of Arabidopsis thaliana. J Mol Biol 187:169–183
Riggs CD, Chrispeels MJ (1990) The expression of phytohemagglutinin genes in Phaseolus vulgaris is associated with organ-specific DNA methylation patterns. Plant Mol Biol 14:629–632
Russell GJ, Follett EAC, Subak-Sharpe JH (1971) The doublestranded DNA of cauliflower mosaic virus. J Gen Virol 11: 129–138
Russell GJ, Walker PMB, Elton RA, Subak-Sharpe JH (1976) Doublet frequency analysis of fractionated vertebrate nuclear DNA. J Mol Biol 108:1–23
Setlow P (1976) Nearest neighbor frequencies in deoxyribonucleic acids. In: Fasman GD (ed) Handbook of biochemistry and molecular biology. CRC Press, Cleveland OH, pp 312–318
Shapiro HS (1976) Distribution of purines and pyrimidines in deoxyribonucleic acids. In: Fasman GD (ed) Handbook of biochemistry and molecular biology. CRC Press, Cleveland OH, pp 241–275
Sinsheimer RL (1955) The action of pancreatic deoxyribonuclease: II. Isomeric dinucleotides. J Biol Chem 215:579–583
Sved J, Bird A (1990) The expected equilibrium of the CpG dinucleotide in vertebrate genomes under a mutation model. Proc Natl Acad Sci USA 87:4692–4696
Swartz MN, Trautner TA, Kornberg A (1962) Enzymatic synthesis of deoxyribonucleic acid: XI. Further studies on nearest neighbor base sequences in deoxyribonucleic acids. J Biol Chem 237:1961–1967
Tykocinski ML, Max EE (1984) CG dinucleotide clusters in MHC genes and in 5′ demethylated genes. Nucleic Acids Res 12:4385–4396
Vanyushin BF, Tkacheva SG, Belozersky AN (1970) Rare bases in animal DNA. Nature 225:948–949
von Kalm L, Vize PD, Smith DR (1986) An under-methylated region in the spacer of ribosomal RNA genes of Lilium henryi. Plant Mol Biol 6:33–39
Wagner I, Capesius I (1981) Determination of 5-methylcytosine from plant DNA by high-performance liquid chromatography. Biochim Biophys Acta 654:52–56
Woodcock DM, Crowther PJ, Diver WP (1987) The majority of methylated deoxycytidines in human DNA are not in the CpG dinucleotide. Biochem Biophys Res Commun 145:888–894
Woodcock DM, Crowther PJ, Doherty J, Jefferson S, DeCruz E, Noyer-Weidner M, Smith SS, Michael MZ, Graham MW (1989) Quantitative evaluation of Escherichia coli host strains for tolerance to cytosine methylation in plasmid and phage recombinants. Nucleic Acids Res 17:3469–3478
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Gardiner-Garden, M., Sved, J.A. & Frommer, M. Methylation sites in angiosperm genes. J Mol Evol 34, 219–230 (1992). https://doi.org/10.1007/BF00162971
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DOI: https://doi.org/10.1007/BF00162971