Achaz G, Palmer S, Kearney M, Maldarelli F, Mellors J W, Coffin J M, Wakeley J
Department of Organismic and Evolutionary Biology, Harvard University, USA.
Mol Biol Evol. 2004 Oct;21(10):1902-12. doi: 10.1093/molbev/msh196. Epub 2004 Jun 23.
A simple nonparameteric test for population structure was applied to temporally spaced samples of HIV-1 sequences from the gag-pol region within two chronically infected individuals. The results show that temporal structure can be detected for samples separated by about 22 months or more. The performance of the method, which was originally proposed to detect geographic structure, was tested for temporally spaced samples using neutral coalescent simulations. Simulations showed that the method is robust to variation in samples sizes and mutation rates, to the presence/absence of recombination, and that the power to detect temporal structure is high. By comparing levels of temporal structure in simulations to the levels observed in real data, we estimate the effective intra-individual population size of HIV-1 to be between 10(3) and 10(4) viruses, which is in agreement with some previous estimates. Using this estimate and a simple measure of sequence diversity, we estimate an effective neutral mutation rate of about 5 x 10(-6) per site per generation in the gag-pol region. The definition and interpretation of estimates of such "effective" population parameters are discussed.
一种简单的群体结构非参数检验方法被应用于来自两名慢性感染个体的gag-pol区域的HIV-1序列的时间间隔样本。结果表明，对于间隔约22个月或更长时间的样本，可以检测到时间结构。该方法最初是为检测地理结构而提出的，通过中性合并模拟对时间间隔样本的性能进行了测试。模拟表明，该方法对样本大小和突变率的变化、重组的存在与否具有鲁棒性，并且检测时间结构的能力很高。通过将模拟中的时间结构水平与实际数据中观察到的水平进行比较，我们估计HIV-1的个体内有效群体大小在10³到10⁴个病毒之间，这与之前的一些估计一致。利用这个估计值和序列多样性的简单度量，我们估计gag-pol区域每个位点每代的有效中性突变率约为5×10⁻⁶。本文讨论了此类“有效”群体参数估计的定义和解释。
