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Volume 29 Issue 1
February 2014
    Citation: Stefan Dang, Yan Wang, Bettina Budeus, Jens Verheyen, Rongge Yang, Daniel Hoffmann. Differential selection in HIV-1 gp120 between subtype B and East Asian variant B' .VIROLOGICA SINICA, 2014, 29(1) : 40-47.  http://dx.doi.org/10.1007/s12250-014-3389-y
    shu

    Differential selection in HIV-1 gp120 between subtype B and East Asian variant B'

    • 1.

      Research Group Bioinformatics, Center of Medical Biotechnology and Faculty of Biology, University of Duisburg-Essen, Essen 45117, Germany

    • 2.

      AIDS and HIV Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China

    • 3.

      Institute of Virology, University of Duisburg-Essen, Essen 45117, Germany

    • Corresponding author: Daniel Hoffmann, daniel.hoffmann@uni-due.de
    • Received Date: 06 October 2013
      Accepted Date: 20 November 2013
      Published Date: 16 January 2014
      Available online: 01 February 2014
    • 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.
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      Differential selection in HIV-1 gp120 between subtype B and East Asian variant B'

        Corresponding author: Daniel Hoffmann, daniel.hoffmann@uni-due.de
      • 1. Research Group Bioinformatics, Center of Medical Biotechnology and Faculty of Biology, University of Duisburg-Essen, Essen 45117, Germany
      • 2. AIDS and HIV Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
      • 3. Institute of Virology, University of Duisburg-Essen, Essen 45117, Germany
      • Received Date: 06 October 2013
      • Accepted Date: 20 November 2013
      • Published Date: 16 January 2014

      Abstract: 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.

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