Differential selection in HIV-1 gp120 between subtype B and East Asian variant B'.
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 k a /k s 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 k a /k s 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 k a /k s values.
Research Group Bioinformatics, Center of Medical Biotechnology and Faculty of Biology, University of Duisburg-Essen, Essen, 45117, Germany.
Stefan
S
Dang
Yan
Y
Wang
Bettina
B
Budeus
Jens
J
Verheyen
Rongge
R
Yang
Daniel
D
Hoffmann
D001208:Asia; D016000:Cluster Analysis; D003062:Codon; D019295:Computational Biology / Q000379:methods; D005060:Europe; D019143:Evolution, Molecular; D005838:Genotype; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics*; D006801:Humans; D059645:Mutation Rate; D009656:North America; D058974:Phylogeography; D017354:Point Mutation; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
D003062:Codon; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1