1887

Journal of General Virology header logo

Volume 86, Issue 5

Overlapping reading frames in closely related human papillomaviruses result in modular rates of selection within E2 Free

Abstract

A core group of four open reading frames (ORFs) is present in all known papillomaviruses (PVs): the E1 and E2 replication/transcription proteins and the L1 and L2 structural proteins. Because they are involved in processes that are essential to PV propagation, the sequences of these proteins are well-conserved. However, sequencing of novel subtypes for human papillomaviruses (HPV) 54 (AE9) and 82 (AE2/IS39), coupled to analysis of four other closely related genital HPV pairs, indicated that E2 has a higher dN/dS ratio than E1, L1 or L2. The elevated ratio is not homogeneous across the length of the ORF, but instead varies with respect to E2's three domains. The E2 hinge region is of particular interest, because its hypervariability (dN/dS>1) differs markedly from the two domains that it joins: the transcription-activation domain and the DNA-binding domain. Deciphering whether the hinge region's high rate of non-synonymous change is the result of positive Darwinian selection or relaxed constraint depends on the evolutionary behaviour of E4, an ORF that overlaps E2. The E2 hinge region is contained within E4 and non-synonymous changes in the hinge are associated with a disproportionate amount of synonymous change in E4, a case of simultaneous positive and purifying selection in overlapping reading frames. Modular rates of selection among E2 domains are a likely consequence of the presence of an embedded E4. E4 appears to be positioned in a part of the HPV genome that can tolerate non-synonymous change and purifying selection of E4 may be indicative of its functional importance.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80747-0
2005-05-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/5/vir861307.html?itemId=/content/journal/jgv/10.1099/vir.0.80747-0&mimeType=html&fmt=ahah

References

  1. Bosch F. X., de Sanjosé S. 2003; Chapter 1: human papillomavirus and cervical cancer – burden and assessment of causality. J Natl Cancer Inst Monogr 31:3–13
     [Google Scholar]
  2. Chan S.-Y., Delius H., Halpern A. L., Bernard H.-U. 1995; Analysis of genomic sequences of 95 papillomavirus types: uniting typing, phylogeny, and taxonomy. J Virol 69:3074–3083
     [Google Scholar]
  3. Comeron J. M. 1999; K-Estimator: calculation of the number of nucleotide substitutions per site and the confidence intervals. Bioinformatics 15:763–764 [CrossRef]
     [Google Scholar]
  4. de Villiers E. M., Fauquet C., Broker T. R., Bernard H.-U., zur Hausen H. 2004; Classification of papillomaviruses. Virology 324:17–27 [CrossRef]
     [Google Scholar]
  5. Eriksson A., Herron J. R., Yamada T., Wheeler C. M. 1999; Human papillomavirus type 16 variant lineages characterized by nucleotide sequence analysis of the E5 coding segment and the E2 hinge region. J Gen Virol 80:595–600
     [Google Scholar]
  6. Fehrmann F., Laimins L. A. 2003; Human papillomaviruses: targeting differentiating epithelial cells for malignant transformation. Oncogene 22:5201–5207 [CrossRef]
     [Google Scholar]
  7. Fujii Y., Kiyotani K., Yoshida T., Sakaguchi T. 2001; Conserved and non-conserved regions in the Sendai virus genome: evolution of a gene possessing overlapping reading frames. Virus Genes 22:47–52 [CrossRef]
     [Google Scholar]
  8. Gauthier J. M., Dillner J., Yaniv M. 1991; Structural analysis of the human papillomavirus type 16-E2 transactivator with antipeptide antibodies reveals a high mobility region linking the transactivation and the DNA-binding domains. Nucleic Acids Res 19:7073–7079 [CrossRef]
     [Google Scholar]
  9. Guyader S., Ducray D. G. 2002; Sequence analysis of Potato leafroll virus isolates reveals genetic stability, major evolutionary events and differential selection pressure between overlapping reading frame products. J Gen Virol 83:1799–1807
     [Google Scholar]
  10. Ham J., Dostatni N., Gauthier J.-M., Yaniv M. 1991; The papillomavirus E2 protein: a factor with many talents. Trends Biochem Sci 16:440–444 [CrossRef]
     [Google Scholar]
  11. Hegde R. S. 2002; The papillomavirus E2 proteins: structure, function, and biology. Annu Rev Biophys Biomol Struct 31:343–360 [CrossRef]
     [Google Scholar]
  12. Hein J., Stovlbaek J. 1995; A maximum-likelihood approach to analyzing nonoverlapping and overlapping reading frames. J Mol Evol 40:181–189 [CrossRef]
     [Google Scholar]
  13. Hughes A. L., Westover K., da Silva J., O'Connor D. H., Watkins D. I. 2001; Simultaneous positive and purifying selection on overlapping reading frames of the tat and vpr genes of simian immunodeficiency virus. J Virol 75:7966–7972 [CrossRef]
     [Google Scholar]
  14. Knipe D. M., Howley P. M., Griffin D. E., Lamb R. A., Martin M. A., Roizman B., Straus S. E. (editors) 2001 Fields Virology , 4th edn. Philadelphia, PA: Lippincott Williams & Wilkins;
     [Google Scholar]
  15. Korber B. 2002; HIV signature and sequence variation analysis. In Computational Analysis of HIV Molecular Sequences pp  55–72 Edited by Rodrigo A. G., Learn G. H. Dordrecht: Kluwer Academic Publishers;
     [Google Scholar]
  16. Krakauer D. C. 2000; Stability and evolution of overlapping genes. Evolution Int J Org Evolution 54:731–739 [CrossRef]
     [Google Scholar]
  17. Longworth M. S., Laimins L. A. 2004; Pathogenesis of human papillomaviruses in differentiating epithelia. Microbiol Mol Biol Rev 68:362–372 [CrossRef]
     [Google Scholar]
  18. Miyata T., Yasunaga T. 1978; Evolution of overlapping genes. Nature 272:532–535 [CrossRef]
     [Google Scholar]
  19. Mizokami M., Orito E., Ohba K., Ikeo K., Lau J. Y. N., Gojobori T. 1997; Constrained evolution with respect to gene overlap of hepatitis B virus. J Mol Evol 44:Suppl 1S83–S90 [CrossRef]
     [Google Scholar]
  20. Muñoz N., Bosch F. X., de Sanjosé S., Herrero R., Castellsagué X., Shah K. V., Snijders P. J. F., Meijer C. J. L. M. 2003; Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348:518–527 [CrossRef]
     [Google Scholar]
  21. Narechania A., Terai M., Chen Z., DeSalle R., Burk R. D. 2004; Lack of the canonical pRB-binding domain in the E7 ORF of artiodactyl papillomaviruses is associated with the development of fibropapillomas. J Gen Virol 85:1243–1250 [CrossRef]
     [Google Scholar]
  22. Nei M., Gojobori T. 1986; Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3:418–426
     [Google Scholar]
  23. Pavesi A. 2000; Detection of signature sequences in overlapping genes and prediction of a novel overlapping gene in hepatitis G virus. J Mol Evol 50:284–295
     [Google Scholar]
  24. Pavesi A., De Iaco B., Granero M. I., Porati A. 1997; On the informational content of overlapping genes in prokaryotic and eukaryotic viruses. J Mol Evol 44:625–631 [CrossRef]
     [Google Scholar]
  25. Peh W. L., Brandsma J. L., Christensen N. D., Cladel N. M., Wu X., Doorbar J. 2004; The viral E4 protein is required for the completion of the cottontail rabbit papillomavirus productive cycle in vivo. J Virol 78:2142–2151 [CrossRef]
     [Google Scholar]
  26. Pfister H., Fuchs P. G. 1994; Anatomy, taxonomy and evolution of papillomaviruses. Intervirology 37:143–149
     [Google Scholar]
  27. Siegel S. 1956 Nonparametric Statistics for the Behavioral Sciences New York: McGraw-Hill;
     [Google Scholar]
  28. Swofford D. L. 1998 paup*. Phylogenetic Analysis Using Parsimony (*and other methods), version 4 Sunderland, MA: Sinauer Associates;
     [Google Scholar]
  29. Tachezy R., Van Ranst M. A., Cruz Y., Burk R. D. 1994; Analysis of short novel human papillomavirus sequences. Biochem Biophys Res Commun 204:820–827 [CrossRef]
     [Google Scholar]
  30. Terai M., Burk R. D. 2002; Identification and characterization of 3 novel genital human papillomaviruses by overlapping polymerase chain reaction: cand HPV89, cand HPV90, and cand HPV91. J Infect Dis 185:1794–1797 [CrossRef]
     [Google Scholar]
  31. Terai M., DeSalle R., Burk R. D. 2002; Lack of canonical E6 and E7 open reading frames in bird papillomaviruses: Fringilla coelebs papillomavirus and Psittacus erithacus timneh papillomavirus. J Virol 76:10020–10023 [CrossRef]
     [Google Scholar]
  32. Thompson J. D., Higgins D. G., Gibson T. J. 1994; clustal w: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680 [CrossRef]
     [Google Scholar]
  33. Van Ranst M., Kaplan J. B., Burk R. D. 1992; Phylogenetic classification of human papillomaviruses: correlation with clinical manifestations. J Gen Virol 73:2653–2660 [CrossRef]
     [Google Scholar]
  34. Van Ranst M., Tachezy R., Delius H., Burk R. D. 1993; Taxonomy of the human papillomaviruses. Papillomavirus Rep 4:61–65
     [Google Scholar]
  35. Walewski J. L., Keller T. R., Stump D. D., Branch A. D. 2001; Evidence for a new hepatitis C virus antigen encoded in an overlapping reading frame. RNA 7:710–721 [CrossRef]
     [Google Scholar]
  36. Yang Z. 1998; Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Mol Biol Evol 15:568–573 [CrossRef]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80747-0
Loading
Overlapping reading frames in closely related human papillomaviruses result in modular rates of selection within E2
J. Gen. Virol. 86, 1307 (2005); https://doi.org/10.1099/vir.0.80747-0
/content/journal/jgv/10.1099/vir.0.80747-0
/content/journal/jgv/10.1099/vir.0.80747-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error