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Journal of Virology, February 2004, p. 1962-1970, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1962-1970.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Comparative Study of Adaptive Molecular Evolution in Different Human Immunodeficiency Virus Groups and Subtypes

Marc Choisy,1 Christopher H. Woelk,2 Jean-François Guégan,1 and David L. Robertson3*

CEPM, UMR CNRS-IRD 9926, Montpellier, France,1 Department of Pathology, University of California—San Diego, La Jolla, California 92093,2 School of Biological Sciences, University of Manchester, Manchester, United Kingdom3

Received 10 July 2003/ Accepted 28 October 2003

Molecular adaptation, as characterized by the detection of positive selection, was quantified in a number of genes from different human immunodeficiency virus type 1 (HIV-1) group M subtypes, group O, and an HIV-2 subtype using the codon-based maximum-likelihood method of Yang and coworkers (Z. H. Yang, R. Nielsen, N. Goldman, and A. M. K. Pedersen, Genetics 155:431-449, 2000). The env gene was investigated further since it exhibited the strongest signal for positive selection compared to those of the other two major HIV genes (gag and pol). In order to investigate the pattern of adaptive evolution across env, the location and strength of positive selection in different HIV-1 sequence alignments was compared. The number of sites having a significant probability of being positively selected varied among these different alignment data sets, ranging from 25 in HIV-1 group M subtype A to 40 in HIV-1 group O. Strikingly, there was a significant tendency for positively selected sites to be located at the same position in different HIV-1 alignments, ranging from 10 to 16 shared sites for the group M intersubtype comparisons and from 6 to 8 for the group O to M comparisons, suggesting that all HIV-1 variants are subject to similar selective forces. As the host immune response is believed to be the dominant driving force of adaptive evolution in HIV, this result would suggest that the same sites are contributing to viral persistence in diverse HIV infections. Thus, the positions of the positively selected sites were investigated in reference to the inferred locations of different epitope types (antibody, T helper, and cytotoxic T lymphocytes) and the positions of N and O glycosylation sites. We found a significant tendency for positively selected sites to fall outside T-helper epitopes and for positively selected sites to be strongly associated with N glycosylation sites.

* Corresponding author. Mailing address: School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom. Phone: 44-161-275-5089. Fax: 44-161-275-5082. E-mail: david.robertson{at}man.ac.uk.

Journal of Virology, February 2004, p. 1962-1970, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1962-1970.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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