An application of population genetic theory to synonymous gene sequence evolution in the human immunodeficiency virus (HIV)

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Abstract
Summary: A population genetic model is developed and then applied to the synonymous gene sequence variation observed in samples of the Human Immunodeficiency Virus Type 1 (HIV-1). The samples, which were taken from several previous studies, contain sequences of the envelope glycoprotein gene (gp 120) of HIV-1. This analysis suggests that the viral population within an infected patient at any specific time is likely to be composed of close relatives. The viruses in a sample are likely to share a recent common ancestor probably due to consistent positive selection for non-synonymous mutations coupled with low recombination in this region of the genome. There is no substantial difference in synonymous evolutionary rate between samples of sequences obtained from Peripheral Blood Mononucleate Cells (PBMCs) and samples taken from blood plasma. This is likely to be due to the high rate of migration between these 2 HIV sub-populations. The mutation rate for the genetic region examined is estimated at 9·20 × 10−4per site per month. Under the assumptions of the estimation procedure, this estimate can be bounded between 8·50 and 9·91 × 10−4with 95% confidence. When coupled with direct estimates of mutation rate, the rate of synonymous evolution suggests that the mean number of generations per month for HIV-1in vivois between 1 and 4.