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Evolutionary Basis of Codon Usage and Nucleotide Composition Bias in Vertebrate DNA Viruses

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Abstract

Understanding the extent and causes of biases in codon usage and nucleotide composition is essential to the study of viral evolution, particularly the interplay between viruses and host cells or immune responses. To understand the common features and differences among viruses we analyzed the genomic characteristics of a representative collection of all sequenced vertebrate-infecting DNA viruses. This revealed that patterns of codon usage bias are strongly correlated with overall genomic GC content, suggesting that genome-wide mutational pressure, rather than natural selection for specific coding triplets, is the main determinant of codon usage. Further, we observed a striking difference in CpG content between DNA viruses with large and small genomes. While the majority of large genome viruses show the expected frequency of CpG, most small genome viruses had CpG contents far below expected values. The exceptions to this generalization, the large gammaherpesviruses and iridoviruses and the small dependoviruses, have sufficiently different life-cycle characteristics that they may help reveal some of the factors shaping the evolution of CpG usage in viruses.

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References

  • Acken UV, Simon D, Grunert F, Döring H-P, Kröger H (1979) Methylation of viral DNA in vivo and in vitro. Virology 99:152–157

    Article  Google Scholar 

  • Ambinder RF, Robertson KD, Tao Q (1999) DNA methylation and the Epstein-Barr virus. Semin Cancer Biol 9:369–375

    Article  PubMed  CAS  Google Scholar 

  • Bernardi G, Bernardi G (1986) Compositional constraints and genome evolution. J Mol Evol 24:1–11

    Article  PubMed  CAS  Google Scholar 

  • Beutler E, Gelbart T, Han J, Koziol JA, Beutler B (1989) Evolution of the genome and the genetic code: Selection at the dinucleotide level by methylation and polyribonucleotide cleavage. Proc Natl Acad Sci USA 86:192–196

    Article  PubMed  CAS  Google Scholar 

  • Breslauer KJ, Frank R, Blocker H, Marky LA (1986) Predicting DNA duplex stability from the base sequence. Proc Natl Acad Sci USA 83:3746–3750

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Burge C, Campbell AM, Karlin S (1992) Over- and under-representation of short oligonucleotides in DNA sequences. Proc Natl Acad Sci USA 89:1358–1362

    Article  PubMed  CAS  Google Scholar 

  • Chamary J-V, Hurst LD (2004) Similar rates but different modes of sequence evolution in introns and at exonic silent sites in rodents, evidence for selectively driven codon usage. Mol Biol Evol 21:1014–1023

    Article  PubMed  CAS  Google Scholar 

  • Cole CN, Conzen SD (2001) Polyomaviridae: the viruses and their replication. In: Knipe DM, Howley PM (eds) Fundamental virology, vol 4. Lippincott Williams and Wilkins, Philadelphia, PA, pp 985–1018

    Google Scholar 

  • De Amicis F, Marchetti S (2000) Intercodon dinucleotides affect codon choice in plant genes. Nucleic Acids Res 28:3339–3345

    Article  PubMed  Google Scholar 

  • Duan J, Antezana MA (2003) Mammalian mutation pressure, synonymous codon choice, and mRNA degradation. J Mol Evol 57:694–701

    Article  PubMed  CAS  Google Scholar 

  • El Antri S, Bittoun P, Mauffret O, Monnot M, Lescot E, Convert O, Fermandjian S (1993a) Effect of distortions in the phosphate backbone conformation of six related octanucleotide duplexes on CD and 31P NMR spectra. Biochemistry 32:7079–7088

    Article  CAS  Google Scholar 

  • El Antri S, Mauffret O, Monnot M, Lescot E, Convert O, Fermandjian S (1993b) Structural deviations at CpG provide a plausible explanation for the high frequency of mutation at this site, Phosphorus nuclear magnetic resonance and circular dichroism studies. J Mol Biol 230:373–378

    Article  CAS  Google Scholar 

  • Gentles AJ, Karlin S (2001) Genome-scale compositional comparisons in eukaryotes. Genome Res 11:540–546

    Article  PubMed  CAS  Google Scholar 

  • Gouy M, Gautier C (1982) Codon usage in bacteria, correlation with gene expressivity. Nucleic Acids Res 10:7055–7047

    PubMed  CAS  Google Scholar 

  • Grantham R, Gautier C, Guoy M, Mercier R, Pave A (1980) Codon catalogue usage and the genome hypothesis. Nucleic Acids Res 8:49–62

    Google Scholar 

  • Grantham R, Perrin P, Mouchiroud D (1986) Patterns in codon usage of different kinds of species. Oxford Surv Evol Biol 3:48–81

    Google Scholar 

  • Grzeskowiak K, Yanagi K, Privé GG, Dickerson RE (1991) The structure of B-helical C-G-A-T-C-G-A-T-C-G and comparison with C-C-A-A-C-G-T-T-G-GJ. Biol Chem 266:8861–8883

    CAS  Google Scholar 

  • Gu W, Zhou T, Ma J, Sun X, Lu Z (2004) Analysis of synonymous codon usage in SARS Coronavirus and other viruses in the Nidovirales. Virus Res 101:155–161

    Article  PubMed  CAS  Google Scholar 

  • Harte MT, Haga IR, Maloney G, Gray P, Reading PC, Bartlett NW, Smith GL, Bowie A, O’Neill AJ (2003) The poxvirus protein A52R targets toll-like receptor signalling complexes to suppress host defense. J Exp Med 197:343–351

    Article  PubMed  CAS  Google Scholar 

  • Howley PM, Lowy DR (2001) Papillomaviruses and their replication. In: Knipe DM, Howley PM (eds) Fundamental virology, vol 4. Lippincott Williams and Wilkins, Philadelphia, PA, pp 1019–1051

    Google Scholar 

  • Jenkins GM, Holmes EC (2003) The extent of codon usage bias in human RNA viruses and its evolutionary origin. Virus Res 92:1–7

    Article  PubMed  CAS  Google Scholar 

  • Jones PA, Rideout WMIII, Shen J-C, Spruck CH, Tsai YC (1992) Methylation, mutation and cancer. Bioessays 14:33–36

    Article  PubMed  CAS  Google Scholar 

  • Kämmer C, Doerfler W (1995) Genomic sequencing reveals absence of DNA methylation in the major late promoter of adenovirus type 2 DNA in the virion and in productively infected cells. FEBS Lett 362:301–305

    Article  PubMed  Google Scholar 

  • Karlin S, Burge C (1995) Dinucleotide relative abundance extremes, a genomic signature. Trends Genet 11:283–290

    Article  PubMed  CAS  Google Scholar 

  • Karlin S, Mrázek J (1997) Compositional differences within and between eukaryotic genomes. Proc Natl Acad Sci USA 94:1027–10232

    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

    PubMed  CAS  Google Scholar 

  • Kress C, Thomassin H, Grange T (2001) Local DNA methylation in vertebrates, how could it be performed and targeted? FEBS Lett 494:135–140

    Article  PubMed  CAS  Google Scholar 

  • Krieg AM (2003) CpG DNA, Trigger of sepsis, mediator of protection, or both? Scand J Infect Dis 35:653–659

    Article  PubMed  CAS  Google Scholar 

  • Lander ES, Linton LM, Birren B, et al. (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921

    Article  PubMed  CAS  Google Scholar 

  • Lund J, Sato A, Medzhitov R, Iwasaki A (2003) Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J Exp Med 198:513–520

    Article  PubMed  CAS  Google Scholar 

  • Lundberg P, Welander P, Han X, Cantin E (2003) Herpes simplex virus type 1 DNA is immunostimulatory in vitro and in vivo. J Virol 77:11158–11169

    Article  PubMed  CAS  Google Scholar 

  • Moss B (2001) Poxviridae: The viruses and their replication. In: Knipe D, Howley P (eds) Fundamental virology, vol 4. Lippincott Williams and Wilkins, Philadelphia, PA, pp 1249–1283

    Google Scholar 

  • Moyer JD, Henderson JF (1985) Compartmentation of intracellular nucleotides in mammalian cells. CRC Crit Rev Biochem 19:45–61

    PubMed  CAS  Google Scholar 

  • Muzyczka N, Berns KI (2001) Parvoviridae: the viruses and their replication. In: Knipe DM, Howley PM (eds) Fundamental virology, vol 4. Lippincott Williams and Wilkins, Philadelphia, PA, pp 1089–1121

    Google Scholar 

  • Novembre JA (2002) Accounting for background nucleotide composition when measuring codon usage bias. Mol Biol Evol 19:1390–1394

    PubMed  CAS  Google Scholar 

  • Oresic M, Shalloway D (1998) Specific correlations between relative synonymous codon usage and protein secondary structure. J Mol Biol 281:31–48

    Article  PubMed  CAS  Google Scholar 

  • Powell JR, Moriyama EN (1997) Evolution of codon usage bias in Drosophila. Proc Natl Acad Sci USA 94:7784–7790

    Article  PubMed  CAS  Google Scholar 

  • Pride DT (2000) SWAAP Version 1.0.0—Sliding windows alignment analysis program: a tool for analyzing patterns of substitutions and similarity in multiple alignments. Distributed by the author

  • Rassa J, Ross SR (2003) Viruses and toll-like receptors. Microbes Infect 5:961–968

    Article  PubMed  CAS  Google Scholar 

  • Rojo G, García-Beato R, Viñuela E, Sala MA, Salas J (1999) Replication of African swine fever virus DNA in infected cells. Virology 257:542–536

    Article  Google Scholar 

  • Schachtel GA, Bucher P, Mocarski ES, Blaisdell BE, Karlin S (1991) Evidence for selective evolution in codon usage in conserved amino acid segments of human alphaherpesvirus proteins. J Mol Evol 33:483–494

    Article  PubMed  CAS  Google Scholar 

  • Shackelton LA, Holmes EC (2004) The evolution of large DNA viruses, combining genomic information of viruses and their hosts. Trends Microbiol 12:458–465

    Article  PubMed  CAS  Google Scholar 

  • Shackelton LA, Parrish CR, Truye U, Holmes EC (2005) High rate of viral evolution associated with the emergence of carnivore parvovirus. Proc Natl Acad Sci USA 102:379–384

    Article  PubMed  CAS  Google Scholar 

  • Sharp PM, Matassi G (1994) Codon usage and genome evolution. Curr Opin Genet Dev 4:851–860

    Article  PubMed  CAS  Google Scholar 

  • Sharp PM, Tuohy TM, Mosurski KR (1986) Codon usage in yeast, cluster analysis clearly differentiates highly and lowly expressed genes. Nucleic Acids Res 14:1525–5143

    Google Scholar 

  • Sharp PM, Stenico M, Peden JF, Lloyd AT (1993) Codon usage, mutational bias, translational selection, or both? Biochem Soc Trans 21:835–841

    PubMed  CAS  Google Scholar 

  • Smith NGC, Eyre-Walker A (2001) Synonymous codon bias is not caused by mutation bias in G + C-rich genes in humans. Mol Biol Evol 18:982–986

    PubMed  CAS  Google Scholar 

  • Stenico M, Lloyd AT, Sharp PM (1994) Codon usage in Caenorhabditis elegans, delineation of translational selection and mutational biases. Nucleic Acids Res 22:2437–2446

    PubMed  CAS  Google Scholar 

  • Strauss EG, Strauss JH, Levine AJ (1996) Virus evolution. In: Fields BN, Knipe DM, Howley PM (eds) Virology. Lippincott-Raven, Philadelphia, PA, pp 153–171

    Google Scholar 

  • Sueoka N (1961) Compositional correlation between deoxyribonucleic acid and protein. Cold Spring Harbor Symp Quant Biol 26:35–43

    PubMed  CAS  Google Scholar 

  • Tao Q, Robertson KD (2003) Stealth technology, how Epstein–Barr virus utilizes DNA methylation to cloak itself from immune detection. Clin Immunol 109:53–63

    Article  PubMed  CAS  Google Scholar 

  • Truyen U, Gruenberg A, Chang SW, Obermaier B, Veijalainen P, Parrish CR (1995) Evolution of the feline-subgroup parvoviruses and the control of canine host range in vivo. J Virol 69:4702–4710

    PubMed  CAS  Google Scholar 

  • Wagner H (2004) The immunobiology of the TLR9 subfamily. Trends Immunol 25:381–386

    Article  PubMed  CAS  Google Scholar 

  • Wagner H, Simon D, Werner E, Gelderblom H, Darai C, Flügel RM (1985) Methylation pattern of fish lymphocystis disease virus DNA. J Virol 53:1005–1007

    PubMed  CAS  Google Scholar 

  • Williams T (1996) The iridoviruses. Adv Virus Res 46:345–412

    Article  PubMed  CAS  Google Scholar 

  • Willis DB, Granoff A (1980) Frog virus 3 DNA is heavily methylated at CpG sequences. Virology 107:250–257

    Article  PubMed  CAS  Google Scholar 

  • Wright F (1990) The “effective number of codons” used in a gene. Gene 87:23–29

    Article  PubMed  CAS  Google Scholar 

  • Wyatt GR (1952) The nucleic acids of some insect viruses. J Gen Physiol 36:201–205

    Article  PubMed  CAS  Google Scholar 

  • Xia X (1996) Maximizing transcription efficiency causes codon usage bias. Genetics 144:1309–1320

    PubMed  CAS  Google Scholar 

  • Zama M (1990) Codon usage and secondary structure of mRNA. Nucleic Acids Symp Ser 22:93–94

    PubMed  CAS  Google Scholar 

  • Zhao K-N, Liu WJ, Frazer IH (2003) Codon usage bias and A + T content variation in human papillomavirus geomes. Virus Res 98:95–104

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was completed under a Howard Hughes Medical Institute Fellowship to L.A.S. and NIH Grant R01AI028385 to C.R.P.

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Authors and Affiliations

  1. Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK

    Laura A. Shackelton

  2. J.A. Baker Institute, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA

    Colin R. Parrish

  3. Center for Infectious Disease Dynamics, Department of Biology, Mueller Laboratory, The Pennsylvania State University, University Park, PA, 16802, USA

    Edward C. Holmes

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  1. Laura A. Shackelton
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  2. Colin R. Parrish
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  3. Edward C. Holmes
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Correspondence to Edward C. Holmes.

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Shackelton, L.A., Parrish, C.R. & Holmes, E.C. Evolutionary Basis of Codon Usage and Nucleotide Composition Bias in Vertebrate DNA Viruses. J Mol Evol 62, 551–563 (2006). https://doi.org/10.1007/s00239-005-0221-1

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