Differential selection in HIV-1 gp120 between subtype B and East Asian variant B’
- 169 Downloads
HIV-1 evolves strongly and undergoes geographic differentiation as it spreads in diverse host populations around the world. For instance, distinct genomic backgrounds can be observed between the pandemic subtype B, prevalent in Europe and North-America, and its offspring clade B’ in East Asia. Here we ask whether this differentiation affects the selection pressure experienced by the virus. To answer this question we evaluate selection pressure on the HIV-1 envelope protein gp120 at the level of individual codons using a simple and fast estimation method based on the ratio ka/ks of amino acid changes to synonymous changes. To validate the approach we compare results to those from a state-of-the-art mixed-effect method. The agreement is acceptable, but the analysis also demonstrates some limitations of the simpler approach. Further, we find similar distributions of codons under stabilizing and directional selection pressure in gp120 for subtypes B and B’ with more directional selection pressure in variable loops and more stabilizing selection in the constant regions. Focusing on codons with increased ka/ks values in B’, we show that these codons are scattered over the whole of gp120, with remarkable clusters of higher density in regions flanking the variable loops. We identify a significant statistical association of glycosylation sites and codons with increased ka/ks values.
Keywordshuman immunodeficiency virus 1 selection pressure genomic background
Unable to display preview. Download preview PDF.
- Chen L, Perlina A, Lee C J. 2004. Positive selection detection in 40,000 human immunodeficiency virus (hiv) type 1 sequences automatically identifies drug resistance and positive fitness mutations in hiv protease and reverse transcriptase. J Virol, 78: 3722–3732.PubMedCentralPubMedCrossRefGoogle Scholar
- Graf M, Shao Y, Zhao Q, Seidl T, Köstler J, Wolf H, and Wagner R. 1998. Cloning and characterization of a virtually full-length hiv type 1 genome from a subtype b’-thai strain representing the most prevalent b-clade isolate in china. AIDS Res Hum Retroviruses, 14: 285–288.PubMedCrossRefGoogle Scholar
- Li Z, Huang Y, Ouyang Y, Shao Y, and Ma L. 2012b. CorMut: Detect the correlated mutations based on selection pressure. R package version 1.2.0.Google Scholar
- Pancera M, Majeed S, Ban Y E, Chen L, Huang C C, Kong L, Kwon Y D, Stuckey J, Zhou T, Robinson J E, Schief W R, Sodroski J, Wyatt R, and Kwong P D. 2010. Structure of hiv-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility. Proc Natl Acad Sci U S A. 107:1166–1171.PubMedCentralPubMedCrossRefGoogle Scholar