Mullins Molecular Retrovirology Lab

  • Department of Microbiology
  • School of Medicine
  • University of Washington

Citation Information

Rousseau CM, Learn GH, Bhattacharya T, Nickle DC, Heckerman D, Chetty S, Brander C, Goulder PJ, Walker BD, Kiepiela P, Korber BT, Mullins JI (2007). Extensive intrasubtype recombination in South African human immunodeficiency virus type 1 subtype C infections. Journal of virology, 81(9), 4492-500. (pubmed)

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.

Supplemental Data

Supplemental Data for Rousseau et al. 2007:

Supplemental Figure: Figure S1: Maximum-likelihood tree of subtype C sequences.

Figure S1: Maximum-likelihood tree of the complete set of subtype C sequences. Outgroup sequences from other subtypes are indicated in gray.

Supplemental Tables