Genome-scale relationships between cytosine methylation and dinucleotide abundances in animals
Genome-scale relationships between cytosine methylation and dinucleotide abundances in animals
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DOI：
10.1016/j.ygeno.2008.03.009
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发表时间：
2008-07-01
期刊：
影响因子：
4.4
通讯作者：
Simmen, Martin W.
中科院分区：
文献类型：
--
作者：
Simmen, Martin W.
在哺乳动物基因组中，CpGs的出现频率仅为预期的五分之一。这被认为是胞嘧啶甲基化和5-甲基胞嘧啶脱胺导致TpG和CpA二核苷酸的结果。CpG缺失与TpG过度相关的推论迄今尚未在基因组水平上得到系统检验。为此，我分析了基因组序列（人类、黑猩猩、小鼠、河豚、斑马鱼、海鞘、果蝇、蚊子和线虫），并总体上评估了CpG缺失、TpG过剩和其他数据与5-甲基胞嘧啶突变有关的假设。在所有甲基化基因组中，随着G + C含量的增加，局部CpG缺失减少。局部TpG盈余在哺乳动物基因组中与G + C水平正相关，而在非哺乳动物基因组中与G + C水平负相关，这可以用甲基化模型下的CpG趋势来解释。二核苷酸丰度与G + C的协方差表明，相关分析应控制G + C。这样做揭示了甲基化基因组中局部CpG和TpG丰度之间的强烈负相关，符合甲基化假说。在哺乳动物中，CpG缺陷也与CpT过量相关，这可能反映了5‘-YCG-3’背景下胞嘧啶突变的增强。对重复屏蔽序列的分析表明，结果不是由重复元素引起的。(C) 2008爱思唯尔公司版权所有。
In mammalian genomes CpGs occur at one-fifth their expected frequency. This is accepted as resulting from cytosine methylation and deamination of 5-methylcytosine leading to TpG and CpA dinucleotides. The corollary that a CpG deficit should correlate with TpG excess has not hitherto been systematically tested at a genomic level. I analyzed genome sequences (human, chimpanzee, mouse, pufferfish, zebrafish, sea squirt, fruitfly, mosquito, and nematode) to do this and generally to assess the hypothesis that CpG deficit, TpG excess, and other data are accountable in terms of 5-methylcytosine mutation. In all methylated genomes local CpG deficit decreases with higher G + C content. Local TpG surplus, while positively associated with G + C level in mammalian genomes but negatively associated with G + C in nonmammalian methylated genomes, is always explicable in terms of the CpG trend under the methylation model. Covariance of dinucleotide abundances with G + C demonstrates that correlation analyses should control for G + C. Doing this reveals a strong negative correlation between local CpG and TpG abundances in methylated genomes, in accord with the methylation hypothesis. CpG deficit also correlates with CpT excess in mammals, which may reflect enhanced cytosine mutation in the context 5'-YCG-3'. Analyses with repeat-masked sequences show that the results are not attributable to repetitive elements. (C) 2008 Elsevier Inc. All rights reserved.