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.
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Chen L, Lee C. 2006. Distinguishing hiv-1 drug resistance, accessory, and viral fitness mutations using conditional selection pressure analysis of treated versus untreated patient samples. Biol Direct, 1:14.
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.
Choisy M, Woelk C H, Guégan J F, and Robertson D L. 2004. Comparative study of adaptive molecular evolution in different human immunodeficiency virus groups and subtypes. J Virol, 78:1962–1970.
Delport W, Poon A F, Frost S D, and Kosakovsky Pond S L. 2010. Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology. Bioinformatics, 26:2455–2457.
Deng X, Liu H, Shao Y, Rayner S, and Yang R. 2008. The epidemic origin and molecular properties of b’: a founder strain of the hiv-1 transmission in asia. AIDS, 22: 1851–1858.
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.
Huelsenbeck J P, Jain S, Frost S W, and Pond S L. 2006. A dirichlet process model for detecting positive selection in proteincoding dna sequences. Proc Natl Acad Sci U S A, 103: 6263–6268.
Katoh K, Misawa K, Kuma K, and Miyata T. 2002. Mafft: a novel method for rapid multiple sequence alignment based on fast fourier transform. Nucleic Acids Res, 30:3059–3066.
Kimura M. 1968. Evolutionary rate at the molecular level. Nature, 217:624–626.
Li W H. 1993. Unbiased estimation of the rates of synonymous and nonsynonymous substitution. J Mol Evol, 36:96–99.
Li Z, He X, Li F, Yang Y, Wang Q, Wang Z, Xing H, Takebe Y, and Shao Y. 2012a. Tracing the origin and history of hiv-1 subtype b’ epidemic in china by near full-length genome analyses. AIDS, 26: 877–884.
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.
Liu J, Bartesaghi A, Borgnia M J, Sapiro G, and Subramaniam S. 2008. Molecular architecture of native hiv-1 gp120 trimers. Nature. 455:109–113.
Mao Y, Wang L, Gu C, Herschhorn A, Xiang S H, Haim H, Yang X, and Sodroski J. 2012. Subunit organization of the membrane-bound hiv-1 envelope glycoprotein trimer. Nat Struct Mol Biol. 19:893–899.
Murrell B, Wertheim J O, Moola S, Weighill T, Scheffler K, and Kosakovsky Pond S L. 2012. Detecting individual sites subject to episodic diversifying selection. PLoS Genet. 8: e1002764.
Nei M, and Gojobori T. 1986. Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol. 3:418–426.
Nielsen R, and Yang Z. 1998. Likelihood models for detecting positively selected amino acid sites and applications to the hiv-1 envelope gene. Genetics. 148:929–936.
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.
Pond S L, Frost S D, Grossman Z, Gravenor M B, Richman D D, and Brown A J. 2006. Adaptation to different human populations by hiv-1 revealed by codon-based analyses. PLoS Comput Biol. 2:e62.
R Development Core Team. 2006. R: A Language and Environment for Statistical Computing. R version 3.0.0; http://www.R-project.org.
Ratner L, Haseltine W, Patarca R, Livak K J, Starcich B, Josephs S F, Doran E R, Rafalski J A, Whitehorn E A, and Baumeister K. 1985. Complete nucleotide sequence of the aids virus, htlv-iii. Nature. 313:277–284.
Rice P, Longden I, and Bleasby A. 2000. Emboss: the european molecular biology open software suite. Trends Genet. 16: 276–277.
Tran E E, Borgnia M J, Kuybeda O, Schauder D M, Bartesaghi A, Frank G A, Sapiro G, Milne J L, and Subramaniam S. 2012. Structural mechanism of trimeric hiv-1 envelope glycoprotein activation. PLoS Pathog. 8:e1002797.
Travers S A, O’Connell M J, McCormack G P, and McInerney J O. 2005. Evidence for heterogeneous selective pressures in the evolution of the env gene in different human immunodeficiency virus type 1 subtypes. J Virol. 79:1836–1841.
Wang W, Nie J, Prochnow C, Truong C, Jia Z, Wang S, Chen X S, and Wang Y. 2013a. A systematic study of the n-glycosylation sites of hiv-1 envelope protein on infectivity and antibody-mediated neutralization. Retrovirology. 10:14.
Wang Y, Rawi R, Wilms C, Heider D, Yang R, and Hoffmann D. 2013b. A small set of succinct signature patterns distinguishes chinese and non-chinese hiv-1 genomes. PLoS One. 8: e58804.
Wernersson R, and Pedersen A G. 2003. Revtrans: Multiple alignment of coding dna from aligned amino acid sequences. Nucleic Acids Res. 31:3537–3539.
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Dang, S., Wang, Y., Budeus, B. et al. Differential selection in HIV-1 gp120 between subtype B and East Asian variant B’. Virol. Sin. 29, 40–47 (2014). https://doi.org/10.1007/s12250-014-3389-y
- human immunodeficiency virus 1
- selection pressure
- genomic background