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Linkage disequilibrium test implies a large effective population number for HIV in vivo.

TitleLinkage disequilibrium test implies a large effective population number for HIV in vivo.
Publication TypeJournal Article
Year of Publication1999
AuthorsIM Rouzine, Coffin, JM
JournalProc Natl Acad Sci U S A
Volume96
Issue19
Pagination10758-63
Date Published1999 Sep 14
ISSN0027-8424
KeywordsComputer Simulation, Evolution, Molecular, Gene Products, env, Genome, Viral, Haplotypes, HIV, Linkage Disequilibrium, Models, Genetic, Monte Carlo Method, Mutation, Stochastic Processes, Time Factors
Abstract

The effective size of the HIV population in vivo, although critically important for the prediction of appearance of drug-resistant variants, is currently unknown. To address this issue, we have developed a simple virus population model, within which the relative importance of stochastic factors and purifying selection for genetic evolution differs over, at least, three broad intervals of the effective population size, with approximate boundaries given by the inverse selection coefficient and the inverse mutation rate per base per cycle. Random drift and selection dominate the smallest (stochastic) and largest (deterministic) population intervals, respectively. In the intermediate (selection-drift) interval, random drift controls weakly diverse populations, whereas strongly diverse populations are controlled by selection. To estimate the effective size of the HIV population in vivo, we tested 200 pro sequences isolated from 11 HIV-infected patients for the presence of a linkage disequilibrium effect which must exist only in small populations. This analysis demonstrated a steady-state virus population of 10(5) infected cells or more, which is either in or at the border of the deterministic regime with respect to evolution of separate bases.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID10485899
PubMed Central IDPMC17956
Grant ListR35 CA 44385 / CA / NCI NIH HHS / United States