Lundstrom R, Tavaré S, Ward R H
Collaborative Research, Inc., Waltham, Massachusetts 012154.
Math Biosci. 1992 Dec;112(2):319-35. doi: 10.1016/0025-5564(92)90030-z.
Mitochondrial DNA data have been used extensively to study evolution and early human origins. These applications require estimates of the rate at which nucleotide substitutions occur in the DNA sequence. We consider the problem of estimating substitution rates in the presence of site-to-site rate variation. A coalescent model is presented that allows for different substitution rates for purines and pyrimidines, as well as more detailed models that allow fast and slow rates within each of the purine and pyrimidine classes. A method for estimating such rates is presented. Even for these simple models of site heterogeneity, there are, typically, insufficient data to obtain reliable estimates of site-specific substitution rates. However, estimates of the average rate across all sites appear to be relatively stable even in the presence of site heterogeneity. Simulations of models with site-to-site variation in mutation rate show that hypervariable sites can produce peaks in the pairwise difference curves that have previously been attributed to population dynamics.
线粒体DNA数据已被广泛用于研究进化和早期人类起源。这些应用需要估计DNA序列中核苷酸替换发生的速率。我们考虑在存在位点间速率变化的情况下估计替换速率的问题。提出了一种合并模型，该模型允许嘌呤和嘧啶具有不同的替换速率，以及更详细的模型，该模型允许在每个嘌呤和嘧啶类别中存在快速和慢速速率。提出了一种估计此类速率的方法。即使对于这些简单的位点异质性模型，通常也没有足够的数据来获得位点特异性替换速率的可靠估计。然而，即使存在位点异质性，所有位点平均速率的估计似乎也相对稳定。对突变率存在位点间变化的模型进行的模拟表明，高变位点可以在成对差异曲线中产生峰值，这些峰值以前被归因于种群动态。
