Borštnik Branko, Pumpernik Danilo
National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
J Bioinform Comput Biol. 2014 Jun;12(3):1450011. doi: 10.1142/S0219720014500115. Epub 2014 Apr 30.
We claim that the apparently enhanced CpG transversions in the form CpG to CpC/GpG or to ApG/CpT are caused by the hypermutable CpG to CpA/TpG transition. The nucleotide replacement counts obtained from the human/chimpanzee/gorilla/orangutan sequence alignments representing the replacements due to the evolutionary species divergence and the results of 1000 genomes project that provide us with the differences due to the intraspecies diversification were analyzed to estimate the ratio of CpG versus non-CpG transversion probabilities. The trinucleotide replacement counts were extracted from the regions that are free of functional constraints. The CpG transversion probabilities based upon the genomic comparisons were found to exceed more than twice the non-CpG transversions. The diversity data emerging from 14 population groups were partitioned in five classes as a function of the parameter quantifying the spread of the polymorphic allele among the group of individuals. The results based upon the human polymorphism exhibit a trend where CpG over non-CpG transversion probability ratio is less and less exceeding unity as the values of the derived allele frequency (DAF) of snps are diminishing. A computer simulation of a simplified model indicates that the phenomenon of the apparent enhancement of CpG transversions can have its source in the interference of the entropic effects with the maximum likelihood methodologies.
我们认为,以CpG到CpC/GpG或到ApG/CpT形式出现的明显增强的CpG颠换是由高度易变的CpG到CpA/TpG转变引起的。分析了从人类/黑猩猩/大猩猩/猩猩序列比对中获得的核苷酸替换计数,这些计数代表了由于进化物种分歧导致的替换,以及1000基因组计划的结果,该计划为我们提供了由于种内多样化导致的差异,以估计CpG与非CpG颠换概率的比率。从无功能限制的区域提取三核苷酸替换计数。基于基因组比较发现,CpG颠换概率超过非CpG颠换概率两倍以上。根据量化多态性等位基因在个体组中扩散的参数,将来自14个人群组的多样性数据分为五类。基于人类多态性的结果显示出一种趋势,即随着单核苷酸多态性(SNP)的衍生等位基因频率(DAF)值减小,CpG与非CpG颠换概率比越来越少地超过1。一个简化模型的计算机模拟表明,CpG颠换明显增强的现象可能源于熵效应与最大似然方法的干扰。