Abstract

Recombination Confounds the Early Evolutionary History of Human Immunodeficiency Virus Type 1: Subtype G Is a Circulating Recombinant Form ▿ Ana B. Abecasis 1 , 2 , Philippe Lemey 1 , 3 , Nicole Vidal 4 , Túlio de Oliveira 3 , † , Martine Peeters 4 , Ricardo Camacho 2 , Beth Shapiro 3 , Andrew Rambaut 3 , ‡ , and Anne-Mieke Vandamme 1 , * 1 Laboratory for Clinical and Epidemiological Virology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium 2 Laboratório de Virologia, Serviço de Imunohemoterapia, Hospital de Egas Moniz, Rua da Junqueira, 126, 1349-019 Lisbon, Portugal 3 Evolutionary Biology Group, Department of Zoology, University of Oxford., South Parks Road, Oxford OX1 3PS, United Kingdom 4 Laboratory Retrovirus, IRD, IRD-UMR 145, 911, Av. Agropolis-BP 64501, 34394 Montpellier Cedex 5, France 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.