BACKGROUND CpGs, the major methylation sites in vertebrate genomes, exhibit a high mutation rate from the methylated form of CpG to TpG/CpA and, therefore, influence the evolution of genome composition. However, the quantitative effects of CpG to TpG/CpA mutations on the evolution of genome composition in terms of the dinucleotide frequencies/proportions remain poorly understood. RESULTS Based on the neutral theory of molecular evolution, we propose a methylation-driven model (MDM) that allows predicting the changes in frequencies/proportions of the 16 dinucleotides and in the GC content of a genome given the known number of CpG to TpG/CpA mutations. The application of MDM to the 10 published vertebrate genomes shows that, for most of the 16 dinucleotides and the GC content, a good consistency is achieved between the predicted and observed trends of changes in the frequencies and content relative to the assumed initial values, and that the model performs better on the mammalian genomes than it does on the lower-vertebrate genomes. The model's performance depends on the genome composition characteristics, the assumed initial state of the genome, and the estimated parameters, one or more of which are responsible for the different application effects on the mammalian and lower-vertebrate genomes and for the large deviations of the predicted frequencies of a few dinucleotides from their observed frequencies. CONCLUSIONS Despite certain limitations of the current model, the successful application to the higher-vertebrate (mammalian) genomes witnesses its potential for facilitating studies aimed at understanding the role of methylation in driving the evolution of genome dinucleotide composition.

中文翻译：

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用于分析基因组中二核苷酸进化的甲基化驱动模型。

背景技术CpGs是脊椎动物基因组中的主要甲基化位点，从CpG的甲基化形式到TpG / CpA表现出很高的突变率，因此影响基因组组成的演变。然而，就二核苷酸频率/比例而言，CpG突变为TpG / CpA对基因组组成演变的定量影响仍然知之甚少。结果基于分子进化的中性理论，我们提出了一种甲基化驱动模型（MDM），该模型可以预测16个二核苷酸的频率/比例和基因组中GC含量的变化（已知CpG到TpG / CpA突变。MDM在已发布的10个脊椎动物基因组中的应用表明，对于16个双核苷酸和GC含量中的大多数，相对于假定的初始值，在频率和内容的变化趋势的预测和观察趋势之间实现了良好的一致性，并且该模型在哺乳动物基因组上的性能优于在较低脊椎动物基因组上的性能。该模型的性能取决于基因组组成特征，基因组的假定初始状态以及估计的参数，其中一个或多个参数对哺乳动物和下脊椎动物的基因组具有不同的应用效果，并且会对基因组的较大偏差负责。从其观察到的频率预测一些二核苷酸的频率。结论尽管当前模型存在某些局限性，