Veterinary Research Communications

, Volume 34, Issue 4, pp 393–404

Analysis of synonymous codon usage in foot-and-mouth disease virus

  • Jian-Hua Zhou
  • Jie Zhang
  • Hao-Tai Chen
  • Li-Na Ma
  • Yong-Sheng Liu
Short Communication


In this study, we calculate the relative synonymous codon usage (RSCU) values and codon usage bias (CUB) values to carry out a comparative analysis of codon usage pattern for open reading frames (ORFs) among 85 samples which belong to all seven serotypes of foot-and-mouth disease virus (FMDV). Although the degree of CUB for ORFs is a relatively slight, there is a significant variation for CUB among different serotypes, which is mainly determined by codon usage pattern depending on RSCU. By comparison with RSCU values for all samples, although RSCU values fail to show the relationship of specific-lineage serotype, there are two main genetic populations existing in FMDV, namely (i) serotypes Asia 1, A, C &O; (ii) serotypes SAT 1, 2 & 3. This interesting characteristic may be formed by the mechanism of RNA virus recombination. The analysis of quantitative & qualitative evaluation based on CUB indicates interesting characteristic of codon usage, which suggests that more FMDV genome diversity may exist in specific-lineage serotypes rather than exist randomly. Furthermore, the relationship between amino acids and codon usage pattern indicates that mutation pressure rather than translational selection in nature is the important determinant of the codon usage bias observed. Our work might give some sight into some characteristics of FMDV ORF and some evolutionary information of this virus.


Foot-and-mouth disease virus Relative synonymous codon usage Codon usage bias Codon usage pattern Genetic population 


  1. Carrillo C, Tulman ER, Delhon G, Lu Z, Carreno A, Vagnozzi A, Kutish GF, Rock DL (2005) Comparative genomics of foot-and-mouth disease virus. J Virol 79, 6487–504.CrossRefPubMedGoogle Scholar
  2. Carrillo C, Lu Z, Borca MV, Vagnozzi A, Kutish GF, Rock DL (2007) Genetic and phenotypic variation of foot-and-mouth disease virus during serial passages in a natural host. J Virol 81, 11341–51.CrossRefPubMedGoogle Scholar
  3. Das S, Paul S, Dutta C (2006) Synonymous codon usage in adenoviruses: influence of mutation, selection and protein hydropathy. Virus Res 117, 227–36.CrossRefPubMedGoogle Scholar
  4. Domingo E (2000) Viruses at the edge of adaptation. Virology 270, 251–53.CrossRefPubMedGoogle Scholar
  5. Domingo E, Escarmis C, Baranowski E, Ruiz-Jarabo C, Carrillo E, Nunez JJ, Sobrino F (2003) Evolution of foot-and-mouth disease virus. Virus Res 91, 47–63.CrossRefPubMedGoogle Scholar
  6. Drake JW, Holland JJ (1999) Mutation rates among RNA viruses. Pro Natl Acad Sci U.S.A. 96, 13910–3.CrossRefGoogle Scholar
  7. Eigen M (1971) Self organization of matter and the evolution of biological macromolecules. Naturwissenschaften 58, 465–523.CrossRefPubMedGoogle Scholar
  8. Ewens WJ, Grant GR (2001) Statisical Methods in Bioinformatics. Springer, New York.Google Scholar
  9. Ghosh TC, Gupta SK, Majumdar S (2000) Studies on codon usage in Entamoeba histolytica. Int J Parasitol 30, 715–22.CrossRefPubMedGoogle Scholar
  10. Gouy M, Gautier C (1982) Codon usage in bacteria: correlation with gene expressivity. Nucleic Acids Res 10, 7055–74.CrossRefPubMedGoogle Scholar
  11. Grantham R, Gautier C, Gouy M, Mercier R, Pave A (1980) Codon catalog usage and the genome hypothesis. Nucleic Acids Res 8, r49–r62.PubMedGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. Grubman MJ, Baxt B (2004) Foot-and-mouth disease. Clin Mirobiol Rev 17, 465–93.CrossRefGoogle Scholar
  14. Gu WJ, Zhou T, Ma JM, Sun X, Lu ZH (2004) Analysis of synonymous codon usage in SARS coronavirus and other viruses in the Nidovirales. Virus Res 101, 155–61.CrossRefPubMedGoogle Scholar
  15. Haydon DT, Samuel AR, Knowles NJ (2001) The generation and persistence of genetic variation in foot-and-mouth disease virus. Prev. Vet. Med. 51, 111–124.CrossRefGoogle Scholar
  16. Jenkins GM, Holmes EC (2003) The extent of codon usage bias in human RNA virus and its evolutionary origin. Virus Res 92, 1–7.CrossRefPubMedGoogle Scholar
  17. Jenkins GM, Pagel M, Gould EA, Zanotto PMdA, Holmes EC (2001) Evolution of base composition and codon usage bias in the genus Flavivirus. J Mol Evol 52, 383–90.PubMedGoogle Scholar
  18. Jolliffe IT (2002) Principal Component Analysis, second edition. Springer-Verlag New York, Inc.Google Scholar
  19. Karlin S, Mrázek J (1996) What drives codon chices in human genes? J Mol Biol 262, 459–72.CrossRefPubMedGoogle Scholar
  20. King AM, McCahon D, Saunders K, Newman JW, Slade WR, (1985) Multiple sites of recombination within the RNA genome of foot-an-mouth disease virus. Virus Res 3, 373–84.CrossRefPubMedGoogle Scholar
  21. Klein J (2009) Understanding the molecular epidemiology of foot-and-mouth disease virus. Infection Genetics and Evolution 9, 205–10.CrossRefGoogle Scholar
  22. Knowles NJ, Samuel AR (2003) Molcular epidemiology of foot-and-mouth disease virus. Virus Res 91, 65–80.CrossRefPubMedGoogle Scholar
  23. Lesnik T, Solomovici J, Deana A, Ehrlich R, Reiss C (2000) Ribosome traffic in E. Coli and regulation of gene expression. J Theor Biol 202, 175–85.CrossRefPubMedGoogle Scholar
  24. Levin DB, Whittome B (2000) Codon usage in nucleopolyhedroviruses. J Gen Virol 81, 2313–25.PubMedGoogle Scholar
  25. Lewis-Rogers N, Mcclellan DA, Crandall KA (2008) The evolution of foot-and-mouth disease virus: Impacts of recombination and selection. Infection, Genetics and Evolution. 8, 786–98.CrossRefPubMedGoogle Scholar
  26. Lloyd AT, Sharp PM (1992) Evolution of codon usage patterns: the extent and nature of divergence between Candida albicans and Saccharomyces cerevisiae. Nucleic Acids Res 20, 5289–95.CrossRefPubMedGoogle Scholar
  27. Majumdar S, Grupta SK, Sundararaj VS, Ghosh TC (1999) Compositional correlation studies among the three different codon position in 12 bacterial genomes. Biochem Biophys Commun 266, 66–71.CrossRefGoogle Scholar
  28. Mardia KV, Kent JT, Bibby JM (1979) Multivariate analysis. Academic press, New York.Google Scholar
  29. Martin A, Bertranpetit J, Oliver JL (1989) Variation in G+C content and codon choice: differences among synonymous codon groups in vertebrate genes. Nucleic Acids Res 17, 6181–9.CrossRefGoogle Scholar
  30. Mason PW, Grubman MJ, Barry B (2003) Molecular basis of pathogenesis of FMDV. Virus Res 91, 9–32.CrossRefPubMedGoogle Scholar
  31. McCahon D, King AM, Roe DS, Slade WR, Newman JW, Cleary AM (1985) Isolation and biochemical characterization of intertypic recombinants of foot-and-mouth disease virus. Virus Res 3, 87–100.CrossRefPubMedGoogle Scholar
  32. Newman JFE, Brown F (1997) Foot-and-mouth disease virus and poliovirus particles contain proteins of the replication complex. J Virol 71, 7657–62.PubMedGoogle Scholar
  33. Ohno H, Sakai H, Washio T, Tomita M (2001) Preferential usage of some minor codons in bacteria. Gene 276, 107–15.CrossRefPubMedGoogle Scholar
  34. Pariente N, Airaksinen A, Domingo E (2003) Mutagenesis versus inhibition in the efficiency of extinction of foot-and-mouth disease virus. J Virol 77, 7131–8.CrossRefPubMedGoogle Scholar
  35. Shackelton LA, Parrish CR, Holmes EC (2006) Evolutionary basis of codon usage and nucleotide composition bias in vertebrate DNA viruses. J Mol Evol 62, 551–63.CrossRefPubMedGoogle Scholar
  36. Sharp PM, Li W H (1986) Codon usage in regulatory genes in Escherichia coli does not reflect selection for ‘rare’ codons. Nucleic Acids Res 14, 7737–49.CrossRefPubMedGoogle Scholar
  37. Sharp PM, Tuohy TM, Mosurski KR (1986) Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes. Nucleic Acids Res 14, 5125–43.CrossRefPubMedGoogle Scholar
  38. Tosh C, Hemadri D, Sanyal A (2002) Evidence of recombination in the capsid-coding region of type A foot-and-mouth disease virus. J Gen Virol 83, 2455–60.PubMedGoogle Scholar
  39. Wilson V, Taylor P, Desselberger U (1988) Crossover regions in foot-and-mouth disease virus (FMDV) recombinants correspond to region of high load secondary structure. Arch Virol 102, 131–9.CrossRefPubMedGoogle Scholar
  40. Xie T, Ding D, Tao X, Dafu D (1998) The relationship between synonymous codon usage and protein structure. FEBS Lett 434, 93–6.CrossRefPubMedGoogle Scholar
  41. Zhou T, Gu WJ, Ma JM, Sun X, Lu ZH (2005) Analysis of synonymous codon usage in H5N1 virus and other influenza A viruses. Biosystems 81, 77–86.CrossRefPubMedGoogle Scholar
  42. Zhou T, Sun X, Lu ZH (2006) Synonymous codon usage in environmental Chlamydia UWE25 reflects an evolution divergence from pathogenic chlamydiae. Gene 368, 117–25.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Jian-Hua Zhou
    • 1
  • Jie Zhang
    • 1
  • Hao-Tai Chen
    • 1
  • Li-Na Ma
    • 1
  • Yong-Sheng Liu
    • 1
  1. 1.Key Laboratory of Animal Virology of Ministry of Agriculture, State Key Laboratory of Veterinary Etiological BiologyLanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesLanzhouChina

Personalised recommendations