Through the functional characterization of HIV envelope genes generated by recombination in the absence of selection, we retrace the early steps shaping patterns of inter-subtype env recombination found in the HIV-1 pandemic. We observe that the mechanism of recombination alone defines regions where recombination occurs at significantly higher rates than elsewhere along the gene. The existence of such regions is strongly suggestive of spatially conserved features in HIV genomes that either promote or restrict recombination between different isolates. The distribution of breakpoints within the gp120 encoding region ( Figure 2B ) is likely due to the distribution of conserved and variable regions, the latter restricting recombination because of the low degree of local sequence identity between the parental sequences [32, 33] .