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Online Journal of Bioinformatics©
Volume 10 (1):165-179, 2009.
Comparative genomic study on context-dependence of CpG mutations:
Acceleration effect of 5’ T nucleotides and new evidence of strand asymmetry in genes.
Wang Y, Leung FC
School of Biological Sciences and Genome Research
Wang Y, Leung FC., Comparative genomic study on context-dependence of CpG mutations: Acceleration effect of 5’ T nucleotides and new evidence of strand asymmetry in genes, Online J Bioinformatics 10 (2):165-179, 2009. Previous studies have reported context-dependence of CpG mutations. In this study, we demonstrate the effect of four CpG flanking nucleotides through comparative genomic analyses. We obtained orthologous genes of C. elegans, fruitfly, sea squirt, zebrafish and human. Analyses on two 5’ flanking positions reveal that T at -2 position can affect T/A to G/C changes at -1 position more significantly than the other nucleotides. As a co-effect of the T/A to G/C changes and CpG mutations, TTCG motif is significantly lower than AACG motif in the zebrafish and human genes. We then studied observed/expected values of dicodons that have a central CpG. The value of TTC•GAA is lowest except in C. elegans, supporting again the context-dependent effect in genes. In addition, we calculated substitutional rates of CpG and four flanking sites. The rate of G is much lower than that of C, and even those of two most adjacent flanking positions for all the species. Mutational rate of CpG sites is facilitated by 5’flanking T nucleotides, and substitutions on CpG sites in genes are more frequently observed on sense strand.
Key words: CpG methylation; context-dependent mutation; CpG deficiency; strand assymmetry.