Phylogenetic Profiling and Stepwise Detection of Recombination Breakpoints in Hiv-1 Sequences from an Individual

Retroviral recombination is an issue in studies of HIV-1 evolution within individuals who harbor a genetically diverse virus population. The nature of retroviral replication is such that recombinant HIV-1 genomes would be expected to be a complex mosaic of parental sequences. However, given the comparatively low levels of virus diversity within an individual, relatively few recombination breakpoints are expected to be detectable. Under these circumstances, a sequential search for breakpoints can be effective. We propose a stepwise approach, based on phylogenetic profiling, in which additional recombination breakpoints are simultaneously tested for and estimated given the location of previously known breakpoints. Such a procedure can be used to assess the number and location of recombination breakpoints in a sequence alignment. We investigate properties of phylogenetic profiling and the associated testing procedure using alignments of constructed nucleotide sequences. The procedure is applied to HIV1 env gene sequences sampled from a patient harboring a heterogeneous population of subtype A virus at seroconversion, and diagnostics based on phylogenetic profiles and tree reconstructions are performed.