THE EXPECTED EQUILIBRIUM OF THE CPG DINUCLEOTIDE IN VERTEBRATE GENOMES UNDER A MUTATION MODEL
THE EXPECTED EQUILIBRIUM OF THE CPG DINUCLEOTIDE IN VERTEBRATE GENOMES UNDER A MUTATION MODEL
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DOI：
10.1073/pnas.87.12.4692
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发表时间：
1990-06-01
影响因子：
11.1
通讯作者：
BIRD, A
中科院分区：
文献类型：
--
作者：
SVED, J;BIRD, A
CpG二核苷酸以约在脊椎动物基因组中的预期频率的20%，这一缺陷被认为是由于CpG甲基化形式向TpG和CpA的高突变率。我们检验了20%的频率代表了新CpG的产生速率和甲基化导致的CpG损失的加速速率之间的平衡的假设。使用该模型，我们计算了CpG二核苷酸的平衡频率的预期降低，并发现观察到的CpG缺陷可以通过在Δ T处从甲基化CpG突变为TpG/CpA来解释。12倍于正常的转换速率，确切的速率取决于转换与颠换的比率。观察到的人α-CpG二核苷酸丢失率珠蛋白未加工假基因，. PSI.α 1的突变，以及该序列中CpG库被新突变的明显补充，与上述参数一致。这些计算表明，将需要2500万年或更少的时间，脊椎动物进化的一小部分时间，CpG频率从未耗尽的水平降低到目前的耗尽水平。
The CpG dinucleotide is present at .apprxeq. 20% of its expected frequency in vertebrate genomes, a deficiency thought due to a high mutation rate from the methylated form of CpG to TpG and CpA. We examine the hypothesis that the 20% frequency represents an equilibrium between rate of creation of new CpGs and accelerated rate of CpG loss from methylation. Using this model, we calculate the expected reduction in the equilibrium frequency of the CpG dinucleotide and find that the observed CpG deficiency can be explained by mutation from methylated CpG to TpG/CpA at .apprxeq. 12 times the normal tansition rate, the exact rate depending on the ratio of transitions to transversions. The observed rate of CpG dinucleotide loss in a human .alpha.-globin nonprocessed pseudogene, .PSI..alpha.1, and the apparent replenishment of the CpG pool in this sequence by new mutations, agree with the above parameters. These calculations indicate that it would take 25 million years or less, a small fraction of the time for vertebrate evolution, for CpG frequency to be reduced from undepleted levels to the current depleted levels.