Figure 1.
Model of HIV copy-choice recombination.
The reverse transcriptase (RT) complex is shown moving from the 3′ end of the donor RNA to the 5′ end. The RNAse activity of RT is indicated by the light grey nucleotides on the donor RNA. The nascent negative DNA strand can be observed to the right of the RT complex. A potential strand-transfer event by RT is indicated by the dashed arrow. The dashed boxes indicate windows of decreased probability of crossover that have been anchored to the 5′ side of each mismatch. The probability of a crossover occurring at each base on the acceptor strand is indicated by p1, p2, or p3 as described in Methods. The plot along the bottom is a representation of each of the probability values across the sequence. For this stretch of 16 nucleotides, the total probability of a crossover occurring is given by the equation shown.
Figure 2.
The significance of local sequence identity to recombination.
The main plot displays the normalized distribution of in vitro breakpoints falling within zones ranging from size 1 to 25 (vertical grey bars); see Baird et al. [21] for further details. The horizontal lines indicate the expected random distribution of breakpoints for the zones. The inset plot shows the normalised frequency of both the in vitro breakpoints and randomly generated breakpoints for zones up to size 25 (arranged in groups of five). On the main plot, error bars on the random distributions (vertical lines) represent one standard error to include 68.3% of the distribution. On the inset, the error bars on the random distributions represent 1.96×standard error to include 95% of the distribution.
Figure 3.
Testing of the recombination models.
The probabilistic distribution of breakpoints as predicted by each model (horizontal lines) compared to the in vitro distribution of breakpoints (vertical grey bars). The three panels correspond to predicted breakpoint distributions that ignored sequence identity (A), prohibited a breakpoint on a mismatch (B) and the full model (C); see Methods for further details. The error bars (vertical lines) on the predicted values represent 1.96×standard error to include 95% of the distribution.
Figure 4.
Implementation of the recombination model.
Comparison of model-predicted breakpoints (horizontal lines) with breakpoint locations from HIV-1 recombinants (vertical bars) [26] from the HIV Sequence Database. White bars indicate where the number of breakpoints for the global data is significantly higher than the prediction for the region, light grey bars indicate where the global data falls within the prediction, while dark grey indicates where the global data is significantly lower than the model prediction. The error bars on the model-predicted values represent 1.645×standard error to include 90% of the distribution. The normalised frequency data (y-axis) have been divided into bins of size 400 nucleotides (x-axis). Below the x-axis, the various genomic regions of the HIV-1 genome are displayed. Note, positioning of genes is relative to a gap-stripped sequence alignment.