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MBE Advance Access originally published online on June 23, 2004
Molecular Biology and Evolution 2004 21(10):1902-1912; doi:10.1093/molbev/msh196
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Molecular Biology and Evolution vol. 21 no. 10 © Society for Molecular Biology and Evolution 2004; all rights reserved.

Research Article

A Robust Measure of HIV-1 Population Turnover Within Chronically Infected Individuals

G. Achaz*, S. Palmer{dagger}, M. Kearney{dagger}, F. Maldarelli{dagger}, J. W. Mellors{ddagger}, J. M. Coffin{dagger} and J. Wakeley*

* Department of Organismic and Evolutionary Biology, Harvard University; {dagger} HIV Drug Resistance Program, NCI, NIH, Frederick, Maryland; and {ddagger} Department of Infectious Diseases, University of Pittsburgh

E-mail: gachaz{at}oeb.harvard.edu.

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 103 and 104 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.

Key Words: intra-host HIV evolution • effective population size • chronically infected individual


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