title: Extensive intrasubtype recombination in South African human immunodeficiency virus type 1 subtype C infections.
abstract: Recombinant human immunodeficiency virus type 1 (HIV-1) strains containing sequences from different viral genetic subtypes (intersubtype) and different lineages from within the same subtype (intrasubtype) have been observed. A consequence of recombination can be the distortion of the phylogenetic signal. Several intersubtype recombinants have been identified; however, less is known about the frequency of intrasubtype recombination. For this study, near-full-length HIV-1 subtype C genomes from 270 individuals were evaluated for the presence of intrasubtype recombination. A sliding window schema (window, 2 kb; step, 385 bp) was used to partition the aligned sequences. The Shimodaira-Hasegawa test detected significant topological incongruence in 99.6% of the comparisons of the maximum-likelihood trees generated from each sequence partition, a result that could be explained by recombination. Using RECOMBINE, we detected significant levels of recombination using five random subsets of the sequences. With a set of 23 topologically consistent sequences used as references, bootscanning followed by the interactive informative site test defined recombination breakpoints. Using two multiple-comparison correction methods, 47% of the sequences showed significant evidence of recombination in both analyses. Estimated evolutionary rates were revised from 0.51%/year (95% confidence interval [CI], 0.39 to 0.53%) with all sequences to 0.46%/year (95% CI, 0.38 to 0.48%) with the putative recombinants removed. The timing of the subtype C epidemic origin was revised from 1961 (95% CI, 1947 to 1962) with all sequences to 1958 (95% CI, 1949 to 1960) with the putative recombinants removed. Thus, intrasubtype recombinants are common within the subtype C epidemic and these impact analyses of HIV-1 evolution.
authors.affiliation: Department of Microbiology, University of Washington, 1959 NE Pacific Street, Box 358070, Seattle, WA 98195-8070, USA. cmr@u.washington.edu
authors.forename: Christine M
authors.initials: CM
authors.lastname: Rousseau
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Learn
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Bhattacharya
authors.forename: David C
authors.initials: DC
authors.lastname: Nickle
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.forename: Senica
authors.initials: S
authors.lastname: Chetty
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Photini
authors.initials: P
authors.lastname: Kiepiela
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
mesh_terms: D019295:Computational Biology; D019143:Evolution, Molecular; D005828:Genetics, Population; D016679:Genome, Viral / Q000235:genetics*; D015658:HIV Infections / Q000235:genetics / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D016013:Likelihood Functions; D008957:Models, Genetic; D010802:Phylogeny; D011995:Recombination, Genetic; D013019:South Africa