Peifer M, Karro J E, von Grünberg H H
Institute of Chemistry, Karl-Franzens University Graz, Graz, Austria.
Bioinformatics. 2008 Oct 1;24(19):2157-64. doi: 10.1093/bioinformatics/btn391. Epub 2008 Jul 28.
In this article we build a model of the CpG dinucleotide substitution rate and use it to challenge the claim that, that rate underwent a sudden mammalian-specific increase approximately 90 million years ago. The evidence supporting this hypothesis comes from the application of a model of neutral substitution rates able to account for elevated CpG dinucleotide substitution rates. With the initial goal of improving that model's accuracy, we introduced a modification enabling us to account for boundary effects arising by the truncation of the Markov field, as well as improving the optimization procedure required for estimating the substitution rates.
When using this modified method to reproduce the supporting analysis, the evidence of the rate shift vanished. Our analysis suggests that the CpG-specific rate has been constant over the relevant time period and that the asserted acceleration of the CpG rate is likely an artifact of the original model.
在本文中，我们构建了一个CpG二核苷酸替换率模型，并用它来质疑一种说法，即该速率在大约9000万年前经历了一次突然的、特定于哺乳动物的增加。支持这一假设的证据来自于一个能够解释升高的CpG二核苷酸替换率的中性替换率模型的应用。最初的目标是提高该模型的准确性，我们引入了一种修正方法，使我们能够考虑到马尔可夫场截断产生的边界效应，并改进估计替换率所需的优化程序。
当使用这种改进方法重现支持性分析时，速率变化的证据消失了。我们的分析表明，在相关时间段内，CpG特异性速率一直保持不变，所声称的CpG速率加速可能是原始模型的一个假象。
