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Archives of Virology

, Volume 164, Issue 2, pp 335–347 | Cite as

A detailed analysis of synonymous codon usage in human bocavirus

  • Snawar HussainEmail author
  • Sahibzada Tasleem Rasool
  • Afzal Haq Asif
Original Article

Abstract

Human bocavirus (HBoV) is a recently discovered parvovirus associated with respiratory and gastroenteric infections in children. To date, four distinct subtypes have been identified worldwide. HBoV1 is the most frequently detected bocavirus in clinical samples derived from the respiratory tract. HBoV has a single-stranded DNA genome, which encodes two nonstructural proteins, NS1 and NP1, and two structural proteins, VP1 and VP2. Despite a large number of available HBoV sequences, the molecular evolution of this virus remains enigmatic. Here, we applied bioinformatic methods to measure the codon usage bias in 156 HBoV genomes and analyzed the factors responsible for preferential use of various synonymous codons. The effective number of codons (ENC) indicates a highly conserved, gene-specific codon usage bias in the HBoV genome. The structural genes exhibit a higher degree of codon usage bias than the non-structural genes. Natural selection emerged as dominant factor influencing the codon usage bias in the HBoV genome. Other factors that influence the codon usage include mutational pressure, gene length, protein properties, and the relative abundance of dinucleotides. The results presented in this study provide important insight into the molecular evolution of HBoV and may serve as a primer for HBoV gene expression studies and development of safe and effective vaccines to prevent infection.

Notes

Acknowledgements

We thank the College of Clinical Pharmacy for providing necessary support to conduct this research. This research was supported by the Deanship of Scientific Research, King Faisal University, grant #160009.

Author contributions

SH, STR and AHA identified the research topic and designed the study. SH collected the data and conducted the analysis. SH, STR and AHA prepared the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This research work does not involve human participants or animals.

Informed consent

Not applicable, as no human participants are involved.

Supplementary material

705_2018_4063_MOESM1_ESM.xlsx (182 kb)
Supplementary material 1 (XLSX 181 kb)

References

  1. 1.
    Akashi H (1997) Codon bias evolution in Drosophila. Population genetics of mutation-selection drift. Gene 205:269–278Google Scholar
  2. 2.
    Allander T, Tammi MT, Eriksson M, Bjerkner A, Tiveljung-Lindell A, Andersson B (2005) Cloning of a human parvovirus by molecular screening of respiratory tract samples. Proc Natl Acad Sci USA 102:12891–12896Google Scholar
  3. 3.
    Arthur JL, Higgins GD, Davidson GP, Givney RC, Ratcliff RM (2009) A novel bocavirus associated with acute gastroenteritis in Australian children. PLoS Pathog 5:e1000391Google Scholar
  4. 4.
    Atkinson NJ, Witteveldt J, Evans DJ, Simmonds P (2014) The influence of CpG and UpA dinucleotide frequencies on RNA virus replication and characterization of the innate cellular pathways underlying virus attenuation and enhanced replication. Nucleic Acids Res 42:4527–4545Google Scholar
  5. 5.
    Bernardi G, Bernardi G (1986) Compositional constraints and genome evolution. J Mol Evol 24:1–11Google Scholar
  6. 6.
    Beutler E, Gelbart T, Han JH, 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 86:192–196Google Scholar
  7. 7.
    Bradel-Tretheway BG, Zhen Z, Dewhurst S (2003) Effects of codon-optimization on protein expression by the human herpesvirus 6 and 7 U51 open reading frame. J Virol Methods 111:145–156Google Scholar
  8. 8.
    Brocchieri L, Karlin S (1994) Geometry of interplanar residue contacts in protein structures. Proc Natl Acad Sci USA 91:9297–9301Google Scholar
  9. 9.
    Bulmer M (1991) The selection-mutation-drift theory of synonymous codon usage. Genetics 129:897–907Google Scholar
  10. 10.
    Butt AM, Nasrullah I, Tong Y (2014) Genome-wide analysis of codon usage and influencing factors in chikungunya viruses. PLoS One 9:e90905Google Scholar
  11. 11.
    Chen SL, Lee W, Hottes AK, Shapiro L, McAdams HH (2004) Codon usage between genomes is constrained by genome-wide mutational processes. Proc Natl Acad Sci USA 101:3480–3485Google Scholar
  12. 12.
    Chinnery HR, McLenachan S, Binz N, Sun Y, Forrester JV, Degli-Esposti MA, Pearlman E, McMenamin PG (2012) TLR9 ligand CpG-ODN applied to the injured mouse cornea elicits retinal inflammation. Am J Pathol 180:209–220Google Scholar
  13. 13.
    Chow BD, Ou Z, Esper FP (2010) Newly recognized bocaviruses (HBoV, HBoV2) in children and adults with gastrointestinal illness in the United States. J Clin Virol 47:143–147Google Scholar
  14. 14.
    Costafreda MI, Perez-Rodriguez FJ, D’Andrea L, Guix S, Ribes E, Bosch A, Pinto RM (2014) Hepatitis A virus adaptation to cellular shutoff is driven by dynamic adjustments of codon usage and results in the selection of populations with altered capsids. J Virol 88:5029–5041Google Scholar
  15. 15.
    Cotmore SF, Agbandje-McKenna M, Chiorini JA, Mukha DV, Pintel DJ, Qiu J, Soderlund-Venermo M, Tattersall P, Tijssen P, Gatherer D, Davison AJ (2014) The family Parvoviridae. Arch Virol 159:1239–1247Google Scholar
  16. 16.
    Cristina J, Moreno P, Moratorio G, Musto H (2015) Genome-wide analysis of codon usage bias in Ebolavirus. Virus Res 196:87–93Google Scholar
  17. 17.
    D’Onofrio G, Ghosh TC, Bernardi G (2002) The base composition of the genes is correlated with the secondary structures of the encoded proteins. Gene 300:179–187Google Scholar
  18. 18.
    Deng ZH, Hao YX, Yao LH, Xie ZP, Gao HC, Xie LY, Zhong LL, Zhang B, Cao YD, Duan ZJ (2014) Immunogenicity of recombinant human bocavirus-1,2 VP2 gene virus-like particles in mice. Immunology 142:58–66Google Scholar
  19. 19.
    Dittmar KA, Goodenbour JM, Pan T (2006) Tissue-specific differences in human transfer RNA expression. PLoS Genet 2:e221Google Scholar
  20. 20.
    Duan J, Antezana MA (2003) Mammalian mutation pressure, synonymous codon choice, and mRNA degradation. J Mol Evol 57:694–701Google Scholar
  21. 21.
    Duret L, Mouchiroud D (1999) Expression pattern and surprisingly, gene length shape codon usage in Caenorhabditis, Drosophila, and Arabidopsis. Proc Natl Acad Sci USA 96:4482–4487Google Scholar
  22. 22.
    Fros JJ, Dietrich I, Alshaikhahmed K, Passchier TC, Evans DJ, Simmonds P (2017) CpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation post-entry. eLife 6:e29112Google Scholar
  23. 23.
    Greenbaum BD, Ghedin E (2015) Viral evolution: beyond drift and shift. Curr Opin Microbiol 26:109–115Google Scholar
  24. 24.
    Gurda BL, Parent KN, Bladek H, Sinkovits RS, DiMattia MA, Rence C, Castro A, McKenna R, Olson N, Brown K, Baker TS, Agbandje-McKenna M (2010) Human bocavirus capsid structure: insights into the structural repertoire of the parvoviridae. J Virol 84:5880–5889Google Scholar
  25. 25.
    Haas J, Park EC, Seed B (1996) Codon usage limitation in the expression of HIV-1 envelope glycoprotein. Curr Biol 6:315–324Google Scholar
  26. 26.
    Han TH, Chung JY, Hwang ES (2009) Human bocavirus 2 in children, South Korea. Emerg Infect Dis 15:1698–1700Google Scholar
  27. 27.
    Hershberg R, Petrov DA (2008) Selection on codon bias. Annu Rev Genet 42:287–299Google Scholar
  28. 28.
    Hooper SD, Berg OG (2000) Gradients in nucleotide and codon usage along Escherichia coli genes. Nucleic Acids Res 28:3517–3523Google Scholar
  29. 29.
    Hu JS, Wang QQ, Zhang J, Chen HT, Xu ZW, Zhu L, Ding YZ, Ma LN, Xu K, Gu YX, Liu YS (2011) The characteristic of codon usage pattern and its evolution of hepatitis C virus. Infect Genet Evol 11:2098–2102Google Scholar
  30. 30.
    Jabbari K, Bernardi G (2004) Cytosine methylation and CpG, TpG (CpA) and TpA frequencies. Gene 333:143–149Google Scholar
  31. 31.
    Jenkins GM, Holmes EC (2003) The extent of codon usage bias in human RNA viruses and its evolutionary origin. Virus Res 92:1–7Google Scholar
  32. 32.
    Kapoor A, Simmonds P, Slikas E, Li L, Bodhidatta L, Sethabutr O, Triki H, Bahri O, Oderinde BS, Baba MM, Bukbuk DN, Besser J, Bartkus J, Delwart E (2010) Human bocaviruses are highly diverse, dispersed, recombination prone, and prevalent in enteric infections. J Infect Dis 201:1633–1643Google Scholar
  33. 33.
    Kapoor A, Hornig M, Asokan A, Williams B, Henriquez JA, Lipkin WI (2011) Bocavirus episome in infected human tissue contains non-identical termini. PLoS One 6:e21362Google Scholar
  34. 34.
    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 68:2889–2897Google Scholar
  35. 35.
    Kumar S, Stecher G, Tamura K (2016) MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 33:1870–1874Google Scholar
  36. 36.
    Kunec D, Osterrieder N (2016) Codon pair bias is a direct consequence of dinucleotide bias. Cell Rep 14:55–67Google Scholar
  37. 37.
    Kyte J, Doolittle RF (1982) A simple method for displaying the hydropathic character of a protein. J Mol Biol 157:105–132Google Scholar
  38. 38.
    Li J, Yang Y, Dong Y, Li Y, Huang Y, Yi Q, Liu K, Li Y (2013) Key elements of the human bocavirus type 1 (HBoV1) promoter and its trans-activation by NS1 protein. Virol J 10:315Google Scholar
  39. 39.
    Li Q, Zhang Z, Zheng Z, Ke X, Luo H, Hu Q, Wang H (2013) Identification and characterization of complex dual nuclear localization signals in human bocavirus NP1: identification and characterization of complex dual nuclear localization signals in human bocavirus NP1. J Gen Virol 94:1335–1342Google Scholar
  40. 40.
    Liu YS, Zhou JH, Chen HT, Ma LN, Pejsak Z, Ding YZ, Zhang J (2011) The characteristics of the synonymous codon usage in enterovirus 71 virus and the effects of host on the virus in codon usage pattern. Infect Genet Evol 11:1168–1173Google Scholar
  41. 41.
    Luo H, Zhang Z, Zheng Z, Ke X, Zhang X, Li Q, Liu Y, Bai B, Mao P, Hu Q, Wang H (2013) Human bocavirus VP2 upregulates IFN-beta pathway by inhibiting ring finger protein 125-mediated ubiquitination of retinoic acid-inducible gene-I. J Immunol 191:660–669Google Scholar
  42. 42.
    Lusebrink J, Schildgen V, Tillmann RL, Wittleben F, Bohmer A, Muller A, Schildgen O (2011) Detection of head-to-tail DNA sequences of human bocavirus in clinical samples. PLoS One 6:e19457Google Scholar
  43. 43.
    Medvedeva YA, Fridman MV, Oparina NJ, Malko DB, Ermakova EO, Kulakovskiy IV, Heinzel A, Makeev VJ (2010) Intergenic, gene terminal, and intragenic CpG islands in the human genome. BMC Genom 11:48Google Scholar
  44. 44.
    Moriyama EN, Powell JR (1998) Gene length and codon usage bias in Drosophila melanogaster, Saccharomyces cerevisiae and Escherichia coli. Nucleic acids Res 26:3188–3193Google Scholar
  45. 45.
    Mueller S, Papamichail D, Coleman JR, Skiena S, Wimmer E (2006) Reduction of the rate of poliovirus protein synthesis through large-scale codon deoptimization causes attenuation of viral virulence by lowering specific infectivity. J Virol 80:9687–9696Google Scholar
  46. 46.
    Ngumbela KC, Ryan KP, Sivamurthy R, Brockman MA, Gandhi RT, Bhardwaj N, Kavanagh DG (2008) Quantitative effect of suboptimal codon usage on translational efficiency of mRNA encoding HIV-1 gag in intact T cells. PLoS One 3:e2356Google Scholar
  47. 47.
    Novembre JA (2002) Accounting for background nucleotide composition when measuring codon usage bias. Mol Biol Evol 19:1390–1394Google Scholar
  48. 48.
    Plotkin JB, Kudla G (2011) Synonymous but not the same: the causes and consequences of codon bias. Nat Rev Genet 12:32–42Google Scholar
  49. 49.
    Puigbo P, Bravo IG, Garcia-Vallve S (2008) CAIcal: a combined set of tools to assess codon usage adaptation. Biol Direct 3:38Google Scholar
  50. 50.
    Qiu J, Soderlund-Venermo M, Young NS (2017) Human parvoviruses. Clin Microbiol Rev 30:43–113Google Scholar
  51. 51.
    Qu XW, Liu WP, Qi ZY, Duan ZJ, Zheng LS, Kuang ZZ, Zhang WJ, Hou YD (2008) Phospholipase A2-like activity of human bocavirus VP1 unique region. Biochem Biophys Res Commun 365:158–163Google Scholar
  52. 52.
    Romero H, Zavala A, Musto H (2000) Codon usage in Chlamydia trachomatis is the result of strand-specific mutational biases and a complex pattern of selective forces. Nucleic acids Res 28:2084–2090Google Scholar
  53. 53.
    Sanchez G, Bosch A, Pinto RM (2003) Genome variability and capsid structural constraints of hepatitis a virus. Journal of virology 77:452–459Google Scholar
  54. 54.
    Shackelton LA, Parrish CR, Holmes EC (2006) Evolutionary basis of codon usage and nucleotide composition bias in vertebrate DNA viruses. J Mol Evol 62:551–563Google Scholar
  55. 55.
    Sharp CP, LeBreton M, Kantola K, Nana A, Diffo Jle D, Djoko CF, Tamoufe U, Kiyang JA, Babila TG, Ngole EM, Pybus OG, Delwart E, Delaporte E, Peeters M, Soderlund-Venermo M, Hedman K, Wolfe ND, Simmonds P (2010) Widespread infection with homologues of human parvoviruses B19, PARV4, and human bocavirus of chimpanzees and gorillas in the wild. J Virol 84:10289–10296Google Scholar
  56. 56.
    Sharp PM, Li WH (1986) An evolutionary perspective on synonymous codon usage in unicellular organisms. J Mol Evol 24:28–38Google Scholar
  57. 57.
    Sharp PM, Li WH (1987) The codon Adaptation Index—a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res 15:1281–1295Google Scholar
  58. 58.
    Shi SL, Jiang YR, Liu YQ, Xia RX, Qin L (2013) Selective pressure dominates the synonymous codon usage in parvoviridae. Virus Genes 46:10–19Google Scholar
  59. 59.
    Simmonds P (2012) SSE: a nucleotide and amino acid sequence analysis platform. BMC Res Notes 5:50Google Scholar
  60. 60.
    Smith DW (1996) Problems of translating heterologous genes in expression systems: the role of tRNA. Biotechnol Prog 12:417–422Google Scholar
  61. 61.
    Soderlund-Venermo M, Lahtinen A, Jartti T, Hedman L, Kemppainen K, Lehtinen P, Allander T, Ruuskanen O, Hedman K (2009) Clinical assessment and improved diagnosis of bocavirus-induced wheezing in children, Finland. Emerg Infect Dis 15:1423–1430Google Scholar
  62. 62.
    Sueoka N (1988) Directional mutation pressure and neutral molecular evolution. Proc Natl Acad Sci USA 85:2653–2657Google Scholar
  63. 63.
    Sun B, Cai Y, Li Y, Li J, Liu K, Li Y, Yang Y (2013) The nonstructural protein NP1 of human bocavirus 1 induces cell cycle arrest and apoptosis in Hela cells. Virology 440:75–83Google Scholar
  64. 64.
    Tewary SK, Zhao H, Shen W, Qiu J, Tang L (2013) Structure of the NS1 protein N-terminal origin recognition/nickase domain from the emerging human bocavirus. J Virol 87:11487–11493Google Scholar
  65. 65.
    Tulloch F, Atkinson NJ, Evans DJ, Ryan MD, Simmonds P (2014) RNA virus attenuation by codon pair deoptimisation is an artefact of increases in CpG/UpA dinucleotide frequencies. eLife 3:e04531Google Scholar
  66. 66.
    Wang M, Liu YS, Zhou JH, Chen HT, Ma LN, Ding YZ, Liu WQ, Gu YX, Zhang J (2011) Analysis of codon usage in Newcastle disease virus. Virus Genes 42:245–253Google Scholar
  67. 67.
    Wang M, Zhang J, Zhou JH, Chen HT, Ma LN, Ding YZ, Liu WQ, Liu YS (2011) Analysis of codon usage in bovine viral diarrhea virus. Arch Virol 156:153–160Google Scholar
  68. 68.
    Wright F (1990) The ‘effective number of codons’ used in a gene. Gene 87:23–29Google Scholar
  69. 69.
    Zhang Z, Zheng Z, Luo H, Meng J, Li H, Li Q, Zhang X, Ke X, Bai B, Mao P, Hu Q, Wang H (2012) Human bocavirus NP1 inhibits IFN-beta production by blocking association of IFN regulatory factor 3 with IFNB promoter. J Immunol 189:1144–1153Google Scholar
  70. 70.
    Zhao B, Yu X, Wang C, Teng Z, Wang C, Shen J, Gao Y, Zhu Z, Wang J, Yuan Z, Wu F, Zhang X, Ghildyal R (2013) High human bocavirus viral load is associated with disease severity in children under five years of age. PLoS One 8:e62318Google Scholar
  71. 71.
    Zhao KN, Gu W, Fang NX, Saunders NA, Frazer IH (2005) Gene codon composition determines differentiation-dependent expression of a viral capsid gene in keratinocytes in vitro and in vivo. Mol Cell Biol 25:8643–8655Google Scholar
  72. 72.
    Zhao S, Zhang Q, Liu X, Wang X, Zhang H, Wu Y, Jiang F (2008) Analysis of synonymous codon usage in 11 human bocavirus isolates. Bio Syst 92:207–214Google Scholar
  73. 73.
    Zhou H, Wang H, Huang LF, Naylor M, Clifford P (2005) Heterogeneity in codon usages of sobemovirus genes. Arch Virol 150:1591–1605Google Scholar
  74. 74.
    Zhou J, Liu WJ, Peng SW, Sun XY, Frazer I (1999) Papillomavirus capsid protein expression level depends on the match between codon usage and tRNA availability. J Virol 73:4972–4982Google Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Snawar Hussain
    • 1
    Email author
  • Sahibzada Tasleem Rasool
    • 1
  • Afzal Haq Asif
    • 1
  1. 1.Department of Biomedical Science, College of Clinical PharmacyKing Faisal UniversityAl-AhsaKingdom of Saudi Arabia

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