Inconsistencies in Estimating the Age of HIV-1 Subtypes Due to Heterotachy
Inconsistencies in Estimating the Age of HIV-1 Subtypes Due to Heterotachy
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DOI：
10.1093/molbev/msr266
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发表时间：
2012-02-01
影响因子：
10.7
通讯作者：
Pond, Sergei L. Kosakovsky
中科院分区：
文献类型：
--
作者：
Wertheim, Joel O.;Fourment, Mathieu;Pond, Sergei L. Kosakovsky
谱系之间的速率异质性是分子进化的一个共同特征，长期以来它一直阻碍着我们准确估计进化分歧事件年龄的能力。放松分子钟的发展，它模拟了不同谱系之间的可变替代率，旨在纠正这个问题。流行性HIV-1 M组的主要亚型被认为是具有不同替代率的密切相关的谱系。在这里，我们报告说，推断最近的共同祖先的所有这些亚型在一个单一的同源性下的一个单一的（宽松）分子时钟产生显着不同的日期为许多亚型比分析每个亚型本身。我们探索各种方法来改善这个问题。我们的结论是，目前的分子测年方法是不足以处理这种类型的替代率变化的HIV-1。通过模拟，我们表明，异根性导致根年龄被高估。
Rate heterogeneity among lineages is a common feature of molecular evolution, and it has long impeded our ability to accurately estimate the age of evolutionary divergence events. The development of relaxed molecular clocks, which model variable substitution rates among lineages, was intended to rectify this problem. Major subtypes of pandemic HIV-1 group M are thought to exemplify closely related lineages with different substitution rates. Here, we report that inferring the time of most recent common ancestor of all these subtypes in a single phylogeny under a single (relaxed) molecular clock produces significantly different dates for many of the subtypes than does analysis of each subtype on its own. We explore various methods to ameliorate this problem. We conclude that current molecular dating methods are inadequate for dealing with this type of substitution rate variation in HIV-1. Through simulation, we show that heterotachy causes root ages to be overestimated.