Genes & Genomics

, Volume 40, Issue 7, pp 767–780 | Cite as

Analysis of synonymous codon usage bias in helicase gene from Autographa californica multiple nucleopolyhedrovirus

  • Hongju Wang
  • Tao Meng
  • Wenqiang Wei
Research Article


The helicase gene of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is not only involved in viral DNA replication, but also plays a role in viral host range. To identify the codon usage bias of helicase of AcMNPV, the codon usage bias of helicase was especially studies in AcMNPV and 41 reference strains of baculoviruses by calculating the codon adaptation index (CAI), effective number of codon (ENc), relative synonymous codon usage (RSCU), and other indices. The helicase of baculovirus is less biased (mean ENc = 50.539 > 40; mean CAI = 0.246). AcMNPV helicase has a strong bias toward the synonymous codons with G and C at the third codon position (GC3s = 53.6%). The plot of GC3s against ENc values revealed that GC compositional constraints are the main factor that determines the codon usage bias of major of helicase. Several indicators supported that the codon usage pattern of helicase is mainly subject to mutation pressure. Analysis of variation in codon usage and amino acid composition indicated AcMNPV helicase shows the significant preference for one or more postulated codons for each amino acid. A cluster analysis based on RSCU values suggested that AcMNPV is evolutionarily closer to members of group I alphabaculovirus. Comparison of the codon usage pattern among E. coli, yeast, mouse, human and AcMNPV showed that yeast is a suitable expression system for AcMNPV helicase. AcMNPV helicase shows weak codon usage bias. This study may help in elucidating the functional mechanism of AcMNPV helicase and the evolution of baculovirus helicases.


AcMNPV helicase Codon usage bias 



This work was supported by grants from the National Natural Science Foundation of China (31501701) and the Plant Foundation for Young Scientists of Henan University (CX0000A40557).

Compliance with ethical standards

Conflict of interest

Author Wenqiang Wei declares that he has no conflict of interest. Author Hongju Wang declares that she has no conflict of interest. Author Tao Meng declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. Auewarakul P (2005) Composition bias and genome polarity of RNA viruses. Virus Res 109:33–37CrossRefPubMedGoogle Scholar
  2. Babbitt GA, Alawad MA, Schulze KV, Hudson AO (2014) Synonymous codon bias and functional constraint on GC3-related DNA backbone dynamics in the prokaryotic nucleoid. Nucleic Acids Res 42:10915–10926CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bideshi DK, Federici BA (2000) The Trichoplusia ni granulovirus helicase is unable to support replication of Autographa californica multicapsid nucleopolyhedrovirus in cells and larvae of T. ni. J Gen Virol 81:1593–1599CrossRefPubMedGoogle Scholar
  4. Buhr F, Jha S, Thommen M, Mittelstaet J, Kutz F, Schwalbe H, Rodnina MV, Komar AA (2016) Synonymous codons direct cotranslational folding toward different protein conformations. Mol Cell 61:341–351CrossRefPubMedPubMedCentralGoogle Scholar
  5. Burge C, Campbell AM, Karlin S (1992) Over- and under-representation of short oligonucleotides in DNA sequences. Proc Natl Acad Sci USA 89:1358–1362CrossRefPubMedPubMedCentralGoogle Scholar
  6. Carbone A, Zinovyev A, Képes F (2003) Codon adaptation index as a measure of dominating codon bias. Bioinformatics 19:2005–2015CrossRefPubMedGoogle Scholar
  7. Corpet F (1988) Multiple sequence alignment with hierarchical clustering. Nucleic Acids Res 16:10881–10890CrossRefPubMedPubMedCentralGoogle Scholar
  8. Croizier G, Croizier L, Argaud O, Poudevigne D (1994) Extension of Autographa californica nuclear polyhedrosis virus host range by interspecific replacement of a short DNA sequence in the p143 helicase gene. Proc Natl Acad Sci USA 91:48–52CrossRefPubMedPubMedCentralGoogle Scholar
  9. Deng W, Wang Y, Liu Z, Cheng H, Xue Y (2014) HemI: a toolkit for illustrating heatmaps. PLoS ONE 9:e111988CrossRefPubMedPubMedCentralGoogle Scholar
  10. Gouy M, Gautier C (1982) Codon usage in bacteria: correlation with gene expressivity. Nucleic Acids Res 10:7055–7074CrossRefPubMedPubMedCentralGoogle Scholar
  11. Grantham R, Gautier C, Gouy M (1980) Codon frequencies in 119 individual genes confirm corsistent choices of degenerate bases according to genome type. Nucleic Acids Res 8:1893–1912CrossRefPubMedPubMedCentralGoogle Scholar
  12. Greenbaum BD, Levine AJ, Bhanot G, Rabadan R (2008) Patterns of evolution and host gene mimicry in influenza and other RNA viruses. PLoS Pathog 4:e1000079CrossRefPubMedPubMedCentralGoogle Scholar
  13. Hamajima R, Kobayashi M, Ikeda M (2015) Identification of amino acid residues of AcMNPV P143 protein involved in rRNA degradation and restricted viral replication in BM-N cells from the silkworm Bombyx mori. Virology 485:244–251CrossRefPubMedGoogle Scholar
  14. Harrison RL, Lynn DE (2007) Genomic sequence analysis of a nucleopolyhedrovirus isolated from the diamondback moth, Plutella xylostella. Virus Genes 35:857–873CrossRefPubMedGoogle Scholar
  15. Herniou EA, Olszewski JA, O’Reilly DR, Cory JS (2004) Ancient coevolution of baculoviruses and their insect hosts. J Virol 78:3244–3251CrossRefPubMedPubMedCentralGoogle Scholar
  16. Hunt RC, Simhadri VL, Iandoli M, Sauna ZE, Kimchi-Sarfaty C (2014) Exposing synonymous mutations. Trends Genet 30:308–321CrossRefPubMedGoogle Scholar
  17. Jiang P, Sun X, Lu Z (2007) Analysis of synonymous codon usage in Aeropyrum pernix K1 and other Crenarchaeota microorganisms. J Genet Genom 34:275–284CrossRefGoogle Scholar
  18. Jiang Y, Deng F, Wang H, Hu Z (2008) An extensive analysis on the global codon usage pattern of baculoviruses. Arch Virol 153:2273CrossRefPubMedGoogle Scholar
  19. Kadir HBA, Payne CC, Crook NE, Fenlon JS, Winstanley D (1999) The comparative susceptibility of the diamondback moth Plutella xylostella and some other major lepidopteran pests of brassica crops to a range of baculoviruses. Biocontrol Sci Technol 9:421–433CrossRefGoogle Scholar
  20. Kumar N, Bera BC, Greenbaum BD, Bhatia S, Sood R, Selvaraj P, Anand T, Tripathi BN, Virmani N (2016) Revelation of influencing factors in overall codon usage bias of equine influenza viruses. PLoS ONE 11:e0154376CrossRefPubMedPubMedCentralGoogle Scholar
  21. McDougal VV, Guarino LA (2001) DNA and ATP binding activities of the baculovirus DNA helicase P143. J Virol 75:7206–7209CrossRefPubMedPubMedCentralGoogle Scholar
  22. Miele SA, Garavaglia MJ, Belaich MN, Ghiringhelli PD (2011) Baculovirus: molecular insights on their diversity and conservation. Int J Evol Biol 2011:379424CrossRefPubMedPubMedCentralGoogle Scholar
  23. Miller LK (1997) The Baculoviruses. Plenum Press, New York, p p35CrossRefGoogle Scholar
  24. Moriyama EN, Powell JR (1997) Codon usage bias and tRNA abundance in Drosophila. J Mol Evol 45:514–523CrossRefPubMedGoogle Scholar
  25. Nasrullah I, Butt AM, Tahir S, Idrees M, Tong Y (2015) Genomic analysis of codon usage shows influence of mutation pressure, natural selection, and host features on Marburg virus evolution. BMC Evol Biol 15:174CrossRefPubMedPubMedCentralGoogle Scholar
  26. Peden J (2005) CodonW, Version 1.4.2. Available at
  27. Plotkin JB, Kudla G (2010) Synonymous but not the same: the causes and consequences of codon bias. Nat Rev Genet 12:nrg2899Google Scholar
  28. Pop C, Rouskin S, Ingolia NT, Han L, Phizicky EM, Weissman JS, Koller D (2014) Causal signals between codon bias, mRNA structure, and the efficiency of translation and elongation. Mol Syst Biol 10:770CrossRefPubMedPubMedCentralGoogle Scholar
  29. Rice P, Longden I, Bleasby A (2000) EMBOSS: the European Molecular Biology Open Software Suite. Trends Genet 16:276CrossRefPubMedGoogle Scholar
  30. Sharp PM, Li W-H (1986) Codon usage in regulatory genes in Escherichia coli does not reflect selection for ‘rare’codons. Nucleic Acids Res 14:7737–7749CrossRefPubMedPubMedCentralGoogle Scholar
  31. Sharp PM, Li W-H (1987) The codon adaptation index-a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res 15:1281–1295CrossRefPubMedPubMedCentralGoogle Scholar
  32. Shi SL, Jiang YR, Yang RS, Wang Y, Qin L (2016) Codon usage in Alphabaculovirus and Betabaculovirus hosted by the same insect species is weak, selection dominated and exhibits no more similar patterns than expected. Infect Genet Evol 44:412CrossRefPubMedGoogle Scholar
  33. SPSS S (2003) Base 12.0 for windows user’s guide. SPSS Inc., ChicagoGoogle Scholar
  34. Sueoka N (1999) Translation-coupled violation of Parity Rule 2 in human genes is not the cause of heterogeneity of the DNA G + C content of third codon position. Gene 238:53–58CrossRefPubMedGoogle Scholar
  35. Vicario S, Moriyama EN, Powell JR (2007) Codon usage in twelve species of Drosophila. BMC Evol Biol 7:226CrossRefPubMedPubMedCentralGoogle Scholar
  36. Wang M, Wang J, Yin F, Tan Y, Deng F, Chen X, Jehle JA, Vlak JM, Hu Z, Wang H (2014) Unraveling the entry mechanism of baculoviruses and its evolutionary implications. J Virol 88:2301–2311CrossRefPubMedPubMedCentralGoogle Scholar
  37. Wang H, Liu S, Zhang B, Wei W (2016) Analysis of synonymous codon usage bias of zika virus and its adaption to the hosts. PLoS ONE 11:e0166260CrossRefPubMedPubMedCentralGoogle Scholar
  38. Wright F (1990) The ‘effective number of codons’ used in a gene. Gene 87:23–29CrossRefPubMedGoogle Scholar
  39. Wu Y-L, Wu C-P, Huang Y-H, Huang S-P, Lo H-R, Chang H-S, Lin P-H, Wu M-C, Chang C-J, Chao Y-C (2014) Identification of a high-efficiency baculovirus DNA replication origin that functions in insect and mammalian cells. J Virol 88:13073–13085CrossRefPubMedPubMedCentralGoogle Scholar
  40. Xu YP, Gu LZ, Lou YH, Cheng RL, Xu HJ, Wang WB, Zhang CX (2012) A baculovirus isolated from wild silkworm encompasses the host ranges of Bombyx mori nucleopolyhedrosis virus and Autographa californica multiple nucleopolyhedrovirus in cultured cells. J Gen Virol 93:2480–2489CrossRefPubMedGoogle Scholar
  41. Yu M, Carstens EB (2012) Choristoneura fumiferana multiple nucleopolyhedrovirus LEF-3–P143 complex can complement DNA replication and budded virus in an AcMNPV LEF-3–P143 double knockout bacmid. J Gen Virol 93:383–388CrossRefPubMedGoogle Scholar
  42. Zhao F, Yu C-h, Liu Y (2017) Codon usage regulates protein structure and function by affecting translation elongation speed in Drosophila cells. Nucleic Acids Res 45:8484–8492CrossRefPubMedPubMedCentralGoogle Scholar
  43. Zhou Z, Dang Y, Zhou M, Li L, Yu C-h, Fu J, Chen S, Liu Y (2016) Codon usage is an important determinant of gene expression levels largely through its effects on transcription. Proc Natl Acad Sci USA 113:E6117–E6125CrossRefPubMedPubMedCentralGoogle Scholar
  44. Zhu Z, Yin F, Liu X, Hou D, Wang J, Zhang L, Arif B, Wang H, Deng F, Hu Z (2014) Genome sequence and analysis of Buzura suppressaria nucleopolyhedrovirus: a group II Alphabaculovirus. PLoS ONE 9:e86450CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The Genetics Society of Korea and Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Basic Medical SciencesHenan UniversityKaifengChina
  2. 2.Huaihe HospitalHenan UniversityKaifengChina

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