Estimating the rate of intersubtype recombination in early HIV-1 group M strains

Abstract

West Central Africa has been implicated as the epicenter of the HIV-1 epidemic, and almost all group M subtypes can be found there. Previous analysis of early HIV-1 group M sequences from Kinshasa in the Democratic Republic of Congo, formerly Zaire, revealed that isolates from a number of individuals fall in different positions in phylogenetic trees constructed from sequences from opposite ends of the genome as a result of recombination between viruses of different subtypes. Here, we use discrete ancestral trait mapping to develop a procedure for quantifying HIV-1 group M intersubtype recombination across phylogenies, using individuals' gag (p17) and env (gp41) subtypes. The method was applied to previously described HIV-1 group M sequences from samples obtained in Kinshasa early in the global radiation of HIV. Nine different p17 and gp41 intersubtype recombinant combinations were present in the data set. The mean number of excess ancestral subtype transitions (NEST) required to map individuals' p17 subtypes onto the gp14 phylogeny samples, compared to the number required to map them onto the p17 phylogenies, and vice versa, indicated that excess subtype transitions occurred at a rate of approximately 7 × 10(-3) to 8 × 10(-3) per lineage per year as a result of intersubtype recombination. Our results imply that intersubtype recombination may have occurred in approximately 20% of lineages evolving over a period of 30 years and confirm intersubtype recombination as a substantial force in generating HIV-1 group M diversity.

Fig 1

Subtype distribution of HIV-1 group M in Kinshasa. The gp41 and p17 regions of HIV-1 group M were sequenced for 57 individuals by Kalish et al. (9). Percentages of individuals infected with potentially pure viruses (i.e., with the same gp41 and p17 subtype) of a given subtype on the basis of maximum likelihood phylogenetic analysis are reported. A total of 26% of the viruses were classified as recombinant (Rec.) on the basis of different subtypes having been assigned to the p17 and gp41 regions.

Fig 2

Maximum clade credibility (MCC) trees for the Kinshasa 1984 data set, colored by ancestral subtype. Maximum clade credibility trees were constructed using BEAST. Branches were colored according to inferred ancestral subtypes, mapping individuals p17 subtypes onto the p17 tree samples (A), patients' p17 subtypes onto the gp41 trees (B), gp41 subtypes onto the gp41 trees (C), and gp41 subtypes onto the p17 trees (D). The number of p17 and gp41 subtype transitions (Markov jumps) across the tree was recorded for each posterior phylogeny sample. Clustering of recombinant sequences can be observed in the MCC trees for two D_F individuals (marked with circles; posterior probabilities of being sister lineages are 0.686 and 0.902 in the p17 and gp41 trees, respectively) and two A_CRF01 individuals (marked with triangles; posterior probabilities of being sister lineages are 0.917 and 0.998 in the p17 and gp41 trees, respectively). Branch lengths are in units of substitutions per site.

Fig 3

Number of inferred p17 ancestral subtype changes across phylogeny samples. The number of ancestral subtype transitions across phylogeny samples was inferred using ancestral trait mapping in BEAST, mapping p17 subtypes onto the p17 and gp41 phylogeny samples. The number of excess subtype transitions (NEST) required to map the ancestral p17 subtypes onto the phylogeny for the “wrong” gene, compared to the number required for mapping them onto the correct phylogeny, was calculated across paired phylogeny samples. Histograms indicate the numbers of subtype transitions across 9,000 post-burn-in samples of phylogenies.

Fig 4

Number of inferred gp41 ancestral subtype changes across phylogeny samples. The number of ancestral subtype transitions across phylogeny samples was inferred using ancestral trait mapping in BEAST, mapping gp41 subtypes onto the p17 and gp41 phylogeny samples. The number of excess subtype transitions (NEST) required to map the ancestral gp41 subtypes onto the phylogeny for the “wrong” gene, compared to the number required for mapping them onto the correct phylogeny, was calculated across paired phylogeny samples. Histograms indicate the number of jumps across 9,000 post-burn-in samples of phylogenies.