Skip to main content

Advertisement

Log in

The tendency of lentiviral open reading frames to become A-rich: constraints imposed by viral genome organization and cellular tRNA availability

  • Articles
  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

Human immunodeficiency virus type 1 (HIV-1) and other lentiviridae demonstrate a strong preference for the A-nucleotide, which can account for up to 40% of the viral RNA genome. The biological mechanism responsible for this nucleotide bias is currently unknown. The increased A-content of these viral genomes corresponds to the typical use of synonymous codons by all members of the lentiviral family (HIV, SIV, BIV, FIV, CAEV, EIAV, visna) and the human spuma retrovirus, but not by other retroviruses like the human T-cell leukemia viruses HTLV-I and HTLV-II. In this article, we analyzed A-bias for all codon groups in all open reading frames of several lentiviruses. The extent of lentiviral codon bias could be related to host cellular translation. By calculating codon bias indices (CBIs), we were able to demonstrate an inverse correlation between the extent of codon bias and the rate of translation of individual reading frames in these viruses. Specifically, the shift toward A-rich codons is more pronounced in pol than in gag lentiviral genes. Since it is known that Gag synthesis exceeds Pol synthesis by a factor of 20 due to infrequent ribosomal frame-shifting during translation of the gap-pol mRNA molecule, we propose that the aminoacyl-tRNA availability in the host cell restricts the lentiviral preference for A-rich codons. In addition, less A-nucleotides were found in regions of the viral genome encoding multiple functions; e.g., overlapping reading frames (tat-rev-env) or in genes that overlap regulatory sequences (nef-LTR region). Finally, the characteristics of lentiviral codon usage are presented as a phylogenetic tree without the need for prior sequence alignment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aota S, Ikemura T (1986) Diversity in G + C content at the third position of codons in vertebrate genes and its cause [published erratum appears in Nucleic Acids Res 1986 Nov 11;14(21):8702]. Nucleic Acids Res 14:6345–6355

    Google Scholar 

  • Barrai I, Scapoli C, Gambari R, Brungnoli F (1991) Frequencies of codons in histones, tubulins and fibrinogen: bias due to interference between transcription signals and protein function. J Theor Biol 152:405–426

    Google Scholar 

  • Bennetzen JL, Hall BD (1982) Codon selection in yeast. J Biol Chem 257:3026–3031

    Google Scholar 

  • Berkhout B, Van Hemert FJ (1994) The unusual nucleotide content of the HIV RNA genome results in a biased amino acid composition of HIV proteins. Nucleic Acids Res 22:1705–1711

    Google Scholar 

  • Bronson CB, Anderson JN (1994) Nucleotide composition as a driving force in the evolution of retroviruses. J Mol Evol 38:506–532

    Google Scholar 

  • Chou KC, Zhang CT (1992) Diagrammatization of codon usage in 339 human immunodeficiency virus proteins and its biological implication. AIDS Res Hum Retroviruses 8:1967–1976

    Google Scholar 

  • Felsenstein J (1993) Phylip (phylogeny inference package) version 3.5c. Distributed by the author. Department of Genetics, University of Washington, Seattle

    Google Scholar 

  • Grantham P, Perrin P (1986) AIDS virus and HTLV-1 differ in codon choices [letter]. Nature 319:727–728

    Google Scholar 

  • Grantham R, Gautier C, Gouy M, Mercier R, Pave A (1980) Codon catalog usage and the genome hypothesis. [Review.] Nucleic Acids Res 8:r49-r62

    Google Scholar 

  • Grantham R, Gautier C, Gouy M, Jacobzone M, Mercier R (1981) Codon catalog usage is a genome strategy modulated for gene expressivity. Nucleic Acids Res 9:r43-r74

    Google Scholar 

  • Gürtler LG, Hauser PH, Eberle J, von Brunn A, Knapp S, Zekeng L, Kaptue L (1994) A new subtype of human immunodeficiency virus type 1 (MVP-5180) from Cameroon. J Virol 68:1581–1585

    Google Scholar 

  • Hatfield D, Feng YX, Lee BJ, Rein A, Levin JG, Oroszlan S (1989) Chromatographic analysis of the aminoacyl-tRNAs which are required for translation of codons at and around the ribosomal frameshift sites of HIV, HTLV-1, and BLV. Virology 173:736–742

    Google Scholar 

  • Huet T, Cheynier R, Meyerhans A, Roelants G, Wain-Hobson S (1990) Genetic organization of a chimpanzee lentivirus related to HIV-1. [See comments.] Nature 345:356–359

    Google Scholar 

  • Ikemura T (1985) Codon usage and tRNA content in unicellular and multicellular organisms. [Review.] Mol Biol Evol 2:13–34

    Google Scholar 

  • Karlin S, Doerfler W, Cardon LR (1994) Why is CpG suppressed in the genomes of virtually all small eukaryotic viruses but not in those of large eukaryotic viruses? J Virol 68:2889–2897

    Google Scholar 

  • Kypr J, Mrazek J, Reich J (1989) Nucleotide composition bias and CpG dinucleotide content in the genomes of HIV and HTLV 1/2. Biochim Biophys Acta 1009:280–282

    Google Scholar 

  • Kypr J, Mrazek J (1987) Unusual codon usage of HIV. [Letter.] Nature 327:20

    Google Scholar 

  • Levin JG, Hatfield DL, Oroszlan S, Rein A (1993) Mechanisms of translational suppression used in the biosynthesis of reverse transcriptase. In: Shalka AM, Goff SP (eds) Reverse transcriptases. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 5–32

    Google Scholar 

  • Long M, Gillespie JH (1991) Codon usage divergence of homologous vertebrate genes and codon usage clock. J Mol Evol 32:6–15

    Google Scholar 

  • Mouchiroud D, Gautier C (1990) Codon usage changes and sequence dissimilarity between human and rat. J Mol Evol 31:81–91

    Google Scholar 

  • Myers G, Wain-Hobson S, Korber B, Smith RF, Pavlakis GN (eds) (1993) A compilation and analysis of nucleic acid and amino acid sequences in human retroviruses and AIDS. Los Alamos National Laboratory, Los Alamos, NM

    Google Scholar 

  • Sharp PM (1986) What can AIDS virus codon usage tell us? [Letter.] Nature 324:114

    Google Scholar 

  • Sharp PM, Cowe E, Higgins DG, Shields DC, Wolfe KH,Wright F (1988) Codon usage patterns in Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens; a review of the considerable within-species diversity [Review]. Nucleic Acids Res 16: 8207–8211

    Google Scholar 

  • Sharp PM, Li WH (1987) The codon adaptation index-a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res 15:1281–1295

    Google Scholar 

  • Vanden Haesevelde M, Decourt JL, De Leys RJ, Vanderborght B, van derGroen G, van Heuverswijn H, Saman E (1994) Genomic cloning and complete sequence analysis of a highly divergent African human immunodeficiency virus isolate. J Virol 68:1586–1596

    Google Scholar 

  • Wada K, Wada Y, Ishibashi F, Gojobori T, Ikemura T (1992) Codon usage tabulated from the GenBank genetic sequence data. Nucleic Acids Res 20(Suppl):2111–2118

    Google Scholar 

  • Zoubak S, Rynditch A, Bernardi G (1992) Compositional bimodality and evolution of retroviral genomes. Gene 119:207–213

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Correspondence to: B. Berkhout

Rights and permissions

Reprints and permissions

About this article

Cite this article

van Hemert, F.J., Berkhout, B. The tendency of lentiviral open reading frames to become A-rich: constraints imposed by viral genome organization and cellular tRNA availability. J Mol Evol 41, 132–140 (1995). https://doi.org/10.1007/BF00170664

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00170664

Key words

Navigation