title: Recombination confounds the early evolutionary history of human immunodeficiency virus type 1: subtype G is a circulating recombinant form.
abstract: Human immunodeficiency virus type 1 (HIV-1) is classified in nine subtypes (A to D, F, G, H, J, and K), a number of subsubtypes, and several circulating recombinant forms (CRFs). Due to the high level of genetic diversity within HIV-1 and to its worldwide distribution, this classification system is widely used in fields as diverse as vaccine development, evolution, epidemiology, viral fitness, and drug resistance. Here, we demonstrate how the high recombination rates of HIV-1 may confound the study of its evolutionary history and classification. Our data show that subtype G, currently classified as a pure subtype, has in fact a recombinant history, having evolved following recombination between subtypes A and J and a putative subtype G parent. In addition, we find no evidence for recombination within one of the lineages currently classified as a CRF, CRF02_AG. Our analysis indicates that CRF02_AG was the parent of the recombinant subtype G, rather than the two having the opposite evolutionary relationship, as is currently proposed. Our results imply that the current classification of HIV-1 subtypes and CRFs is an artifact of sampling history, rather than reflecting the evolutionary history of the virus. We suggest a reanalysis of all pure subtypes and CRFs in order to better understand how high rates of recombination have influenced HIV-1 evolutionary history.
authors.affiliation: Katholieke Universiteit Leuven, Laboratory for Clinical and Epidemiological Virology, AIDS Reference Laboratory, Rega Institute and University Hospitals, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Abecasis
authors.forename: Philippe
authors.initials: P
authors.lastname: Lemey
authors.forename: Nicole
authors.initials: N
authors.lastname: Vidal
authors.forename: Túlio
authors.initials: T
authors.lastname: de Oliveira
authors.forename: Martine
authors.initials: M
authors.lastname: Peeters
authors.forename: Ricardo
authors.initials: R
authors.lastname: Camacho
authors.forename: Beth
authors.initials: B
authors.lastname: Shapiro
authors.forename: Andrew
authors.initials: A
authors.lastname: Rambaut
authors.forename: Anne-Mieke
authors.initials: AM
authors.lastname: Vandamme
mesh_terms: D016477:Artifacts; D001483:Base Sequence; D019143:Evolution, Molecular; D016679:Genome, Viral / Q000235:genetics*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011995:Recombination, Genetic; D017423:Sequence Analysis, RNA