The predicted sensitivity of HIV-1M proteins to recombinational disruption.

<p>(<b>A</b>) Depicted are the means (black lines) and ranges (gray backgrounds) of predicted degrees of recombination-induced folding disruption in various HIV-1 proteins (those for which suitable atomic resolution three dimensional structures are available). The white areas interspersed between the gray areas are positions where there was no protein structure data available or where there were extra amino acids inserted into the alignment that were not present in the protein structure used. For all genome regions that had associated protein structure data, all conceivable single breakpoint recombinants were simulated using parental sequences that resembled as closely as possible the parental sequences of actual recombinant viruses with single detectable recombination breakpoints in these genome regions. Amino acid substitution rates and breakpoint positions occurring in these actual HIV-1 recombinants are displayed at the top of the figure. (<b>B</b>) Recombination breakpoint density plot illustrating breakpoint positions detected across 434 detectable HIV-1M recombination events (After <a href="" target="_blank">[14]</a>). Light and dark grey areas respectively indicate the 95% and 99% confidence intervals of breakpoint numbers that would have been detectable in different genome locations under random recombination. The grey areas undulate with degrees of sequence conservation because recombination events are more easily detectable in genome regions that are genetically diverse. Note firstly that the peaks of the plots in <b>A</b> indicate recombination breakpoint positions that are predicted to have the greatest disruptive effects on protein folding, and secondly that in actual recombinant HIV-1M genomes sampled from nature these “disruptive breakpoint positions” tend to correspond in plot <b>B</b> with regions of low recombination breakpoint densities.</p>