The inference of stepwise changes in substitution rates using serial sequence samples
The inference of stepwise changes in substitution rates using serial sequence samples
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DOI：
10.1093/oxfordjournals.molbev.a003920
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发表时间：
2001-07-01
影响因子：
10.7
通讯作者：
Rodrigo, AG
中科院分区：
文献类型：
--
作者：
Drummond, A;Forsberg, R;Rodrigo, AG
通常情况下，分子序列并不按照严格的时钟方式进化。相反，替代率的变化可能有许多原因，包括选择压力和有效种群规模的变化，以及平均世代时间的变化。在这里，我们提出了两种新的方法来估计取代率的逐步变化时，连续采样的分子序列是可用的。这些方法基于带有日期提示（MRDT）模型的多个速率，并允许在不同的时间间隔内估计不同的速率。这些间隔可以对应于采样间隔或对应于优先定义的间隔，该间隔与获得串行样本的时间不一致。描述了两种获得多速率估计的方法。第一个是Rambaut提出的基于系统发育的最大似然估计方法的扩展。二是对Drummond和Rodrigo使用的两两距离最小二乘方法进行了新的参数化。这些方法的效用证明了在34个月期间从单个患者获得的5个不同采样时间的HIV序列的谱系。
It is frequently true that molecular sequences do not evolve in a strictly clocklike manner. Instead, substitution rate may vary for a number of reasons, including changes in selection pressure and effective population size, as well as changes in mean generation time. Here we present two new methods for estimating stepwise changes in substitution rates when serially sampled molecular sequences are available. These methods are based on multiple rates with dated tips (MRDT) models and allow different rates to be estimated for different intervals of time. These intervals may correspond to the sampling intervals or to a priori-defined intervals that are not coincident with the times the serial samples are obtained. Two methods for obtaining estimates of multiple rates are described. The first is an extension of the phylogeny-based maximum-likelihood estimation procedure introduced by Rambaut. The second is a new parameterization of the pairwise distance least-squares procedure used by Drummond and Rodrigo. The utility of these methods is demonstrated on a genealogy of HIV sequences obtained at five different sampling times from a single patient over a period of 34 months.