標題: DNA Methylation is Associated with an Increased Level of Conservation at Nondegenerate Nucleotides in Mammals
作者: Chuang, Trees-Juen
Chen, Feng-Chi
生物科技學系
Department of Biological Science and Technology
關鍵字: DNA methylation;methylation-associated mutation;single-nucleotide evolution;degeneracy of nucleotide;genomics
公開日期: 1-二月-2014
摘要: DNA methylation at CpG dinucleotides can significantly increase the rate of cytosine-to-thymine mutations and the level of sequence divergence. Although the correlations between DNA methylation and genomic sequence evolution have been widely studied, an unaddressed yet fundamental question is how DNA methylation is associated with the conservation of individual nucleotides in different sequence contexts. Here, we demonstrate that in mammalian exons, the correlations between DNA methylation and the conservation of individual nucleotides are dependent on the type of exonic sequence (coding or untranslated), the degeneracy of coding nucleotides, background selection pressure, and the relative position (first or nonfirst exon in the transcript) where the nucleotides are located. For untranslated and nonzero-fold degenerate nucleotides, methylated sites are less conserved than unmethylated sites regardless of background selection pressure and the relative position of the exon. For zero-fold degenerate (or nondegenerate) nucleotides, however, the reverse trend is observed in nonfirst coding exons and first coding exons that are under stringent background selection pressure. Furthermore, cytosine-to-thymine mutations at methylated zero-fold degenerate nucleotides are predicted to be more detrimental than those that occur at unmethylated nucleotides. As zero-fold and nonzero-fold degenerate nucleotides are very close to each other, our results suggest that the "functional resolution" of DNA methylation may be finer than previously recognized. In addition, the positive correlation between CpG methylation and the level of conservation at zero-fold degenerate nucleotides implies that CpG methylation may serve as an "indicator" of functional importance of these nucleotides.
URI: http://dx.doi.org/10.1093/molbev/mst208
http://hdl.handle.net/11536/23826
ISSN: 0737-4038
DOI: 10.1093/molbev/mst208
期刊: MOLECULAR BIOLOGY AND EVOLUTION
Volume: 31
Issue: 2
起始頁: 387
結束頁: 396
顯示於類別:期刊論文


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  1. 000330836900013.pdf