%0 Journal Article
%T Substitution rate variation at human CpG sites correlates with non-CpG divergence, methylation level and GC content
%A Carina F Mugal
%A Hans Ellegren
%J Genome Biology
%D 2011
%I BioMed Central
%R 10.1186/gb-2011-12-6-r58
%X Here, we use genome-wide methylation data from human sperm cells to investigate the impact of DNA methylation on the CpG substitution rate in introns of human genes. We find that there is a significant correlation between the extent of methylation and the substitution rate at CpG sites. Further, we show that the CpG substitution rate is positively correlated with non-CpG divergence, suggesting susceptibility to factors responsible for the general mutation rate in the genome, and negatively correlated with GC content. We only observe a minor contribution of gene expression level, while recombination rate appears to have no significant effect.Our study provides the first direct empirical support for the hypothesis that variation in the level of germ line methylation contributes to substitution rate variation at CpG sites. Moreover, we show that other genomic features also impact on CpG substitution rate variation.The rate of germ line mutation is the ultimate parameter governing the amount of genetic diversity within populations and the divergence between species. There is extensive variation in mutation rate within genomes and a number of genomic features have been shown to correlate with this rate variation, both at the whole-chromosome level and at regional as well as local levels [1-5]. Examples of factors suggested to be related to mutation rate variation are genetic recombination [6,7], transcription [8,9], replication [10,11], chromatin structure [12,13], distance to telomeres [5], exon density [14] and sequence variables, such as the local GC content [14,15]. Several of these factors are strongly interrelated with each other, which complicates unraveling the driving forces of mutation rate variation.Sequence context effects modulate the mutation rate at individual nucleotide sites [16]. The most well-known and strongest of these effects is the about one order of magnitude higher frequency of C to T substitutions in CpG dinucleotides than that of other transiti
%U http://genomebiology.com/2011/12/6/R58