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. 2006 Mar 23:6:28.
doi: 10.1186/1471-2148-6-28.

Population genetic estimation of the loss of genetic diversity during horizontal transmission of HIV-1

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Population genetic estimation of the loss of genetic diversity during horizontal transmission of HIV-1

Charles T T Edwards et al. BMC Evol Biol. .

Abstract

Background: Genetic diversity of the human immunodeficiency virus type 1 (HIV-1) population within an individual is lost during transmission to a new host. The demography of transmission is an important determinant of evolutionary dynamics, particularly the relative impact of natural selection and genetic drift immediately following HIV-1 infection. Despite this, the magnitude of this population bottleneck is unclear.

Results: We use coalescent methods to quantify the bottleneck in a single case of homosexual transmission and find that over 99% of the env and gag diversity present in the donor is lost. This was consistent with the diversity present at seroconversion in nine other horizontally infected individuals. Furthermore, we estimated viral diversity at birth in 27 infants infected through vertical transmission and found there to be no difference between the two modes of transmission.

Conclusion: Assuming the bottleneck at transmission is selectively neutral, such a severe reduction in genetic diversity has important implications for adaptation in HIV-1, since beneficial mutations have a reduced chance of transmission.

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Figures

Figure 1
Figure 1
Phylogenetic relationship of (a) env V1-V4 and (b) gag p24 sequences. Maximum likelihood phylogenies depicting the relationship between sequences from donor and recipient, illustrating the reduction in genetic diversity at transmission. Horizontal branch lengths are drawn on a scale of nucleotide changes per site. Branches leading to recipient sequences are highlighted in red, with the day of sample collection relative to the first recipient sample (day 0) shown for each sequence.
Figure 2
Figure 2
Reconstructed demographic profiles for (a) env V1-V4 and (b) gag p24. Estimates of are shown on a log scale against time backwards since the most recent sample. Only days on which sequences were sampled are shown, measured relative to the first recipient sample (day 0). Mean estimates of obtained from the best fit Logistic-Constant demographic model and the Bayesian skyline plot are shown with their HPD confidence bounds.
Figure 3
Figure 3
Effective population size at transmission NRτ(ttrans). The marginal posterior probability density of NRτ(ttrans) is shown for both env V1-V4 and gag p24. The shaded area represents the uniform prior distribution that was used, with a minimum bound of one.

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