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Mol Biol (Mosk). 1987 Jul-Aug;21(4):1099-109.

[The loss of dinucleotides CpG from DNA. IV. Methylation and divergence of genes and pseudogenes of small nuclear RNA].

[Article in Russian]


The frequency of neighboring base pairs in nucleotide sequences of over 80 genes and pseudogenes of low molecular weight RNAs U1-U8, 4.5S and 7S in different eukaryotes was determined. The probable frequency of CpG----TpG + CpA substitutions, caused as a result of the deamination of 5-methylcytosine residues in DNA, was determined. It was found that the genes of small RNAs do not reveal a single level of CpG methylation for all the species studied. In most cases CpG in the genes of U1, 4.5S and 7S RNA are methylated, whereas in the genes of U2-U6-RNA these sites must have never been subjected to methylation. Nearly all the investigated pseudogenes of different small RNAs are strongly methylated due to a considerable lack of CpG. It was established that CpG----TpG + CpA transitions may amount to as much third of all the mutations accumulated in the genes of the same RNAs in different species. Such transitions in pseudogenes may account for 40% of all the nucleotide substitutions. This disproportionately high level of mutations in CpG dinucleotides (3-5-fold higher than in other DNA dupletes) must be the direct result of the methylation of these sites. Consequently, CpG methylation causes a dramatic acceleration of the divergence rate of DNA sequences. It has been concluded that protection of most vital genes against methylation is one of the essential conditions for sustaining the high level of stability of the macromolecular structure and for the reliability of macromolecular functioning in a cell.

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