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. 1990 Oct 11;18(19):5793–5797. doi: 10.1093/nar/18.19.5793

Selection against CpG dinucleotides in lentiviral genes: a possible role of methylation in regulation of viral expression.

E G Shpaer 1, J I Mullins 1
PMCID: PMC332316  PMID: 2170945

Abstract

Extremely low frequencies of CpG dinucleotides are found in the genomes of the lentivirus subfamily of retroviruses, including the human, simian and feline immunodeficiency viruses (HIV1, HIV2, SIV, and FIV, respectively), equine infectious anemia virus (EIAV), and the ovine lentivirus, Visna. The occurrence of CpG dinucleotides is greater in the 2-3 (NCG) than in the 1-2 (CGN) codon-defined frame, as well as in the gag and env genes, compared to the more conserved pol gene. These differences suggest that CpG depletion in lentiviruses occurs as a result of selection against CpG rather than due to mutational bias, the latter is responsible for low CpG frequencies in vertebrate genomes. CpG levels in the onco-retrovirus subfamily are reduced to a lesser extent, principally due to mutational bias. The difference between the retrovirus subfamilies appears to reflect their evolutionary origin, that is, lentiviruses have no known endogenous counterparts whereas most oncoviruses have endogenous cellular counterparts with which they can undergo recombination. Furthermore, we suggest that the number of CpG dinucleotides in a lentiviral genome determines the maximum potential DNA methylation level of the provirus, which in turn affects viral transcription in host cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bednarik D. P., Mosca J. D., Raj N. B. Methylation as a modulator of expression of human immunodeficiency virus. J Virol. 1987 Apr;61(4):1253–1257. doi: 10.1128/jvi.61.4.1253-1257.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bird A. P. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. doi: 10.1038/321209a0. [DOI] [PubMed] [Google Scholar]
  3. Bird A. P. DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res. 1980 Apr 11;8(7):1499–1504. doi: 10.1093/nar/8.7.1499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cedar H. DNA methylation and gene activity. Cell. 1988 Apr 8;53(1):3–4. doi: 10.1016/0092-8674(88)90479-5. [DOI] [PubMed] [Google Scholar]
  5. Cooper D. N. Eukaryotic DNA methylation. Hum Genet. 1983;64(4):315–333. doi: 10.1007/BF00292363. [DOI] [PubMed] [Google Scholar]
  6. Cooper D. N., Gerber-Huber S. DNA methylation and CpG suppression. Cell Differ. 1985 Sep;17(3):199–205. doi: 10.1016/0045-6039(85)90488-9. [DOI] [PubMed] [Google Scholar]
  7. Coulondre C., Miller J. H., Farabaugh P. J., Gilbert W. Molecular basis of base substitution hotspots in Escherichia coli. Nature. 1978 Aug 24;274(5673):775–780. doi: 10.1038/274775a0. [DOI] [PubMed] [Google Scholar]
  8. Dewhurst S., Embretson J. E., Anderson D. C., Mullins J. I., Fultz P. N. Sequence analysis and acute pathogenicity of molecularly cloned SIVSMM-PBj14. Nature. 1990 Jun 14;345(6276):636–640. doi: 10.1038/345636a0. [DOI] [PubMed] [Google Scholar]
  9. Doolittle R. F., Feng D. F., Johnson M. S., McClure M. A. Origins and evolutionary relationships of retroviruses. Q Rev Biol. 1989 Mar;64(1):1–30. doi: 10.1086/416128. [DOI] [PubMed] [Google Scholar]
  10. Feng D. F., Doolittle R. F. Progressive sequence alignment as a prerequisite to correct phylogenetic trees. J Mol Evol. 1987;25(4):351–360. doi: 10.1007/BF02603120. [DOI] [PubMed] [Google Scholar]
  11. Gardiner-Garden M., Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987 Jul 20;196(2):261–282. doi: 10.1016/0022-2836(87)90689-9. [DOI] [PubMed] [Google Scholar]
  12. Gautsch J. W., Wilson M. C. Delayed de novo methylation in teratocarcinoma suggests additional tissue-specific mechanisms for controlling gene expression. Nature. 1983 Jan 6;301(5895):32–37. doi: 10.1038/301032a0. [DOI] [PubMed] [Google Scholar]
  13. Groffen J., Heisterkamp N., Blennerhassett G., Stephenson J. R. Regulation of viral and cellular oncogene expression by cytosine methylation. Virology. 1983 Apr 15;126(1):213–227. doi: 10.1016/0042-6822(83)90473-7. [DOI] [PubMed] [Google Scholar]
  14. Hanai R., Wada A. Doublet preference and gene evolution. J Mol Evol. 1990 Feb;30(2):109–115. doi: 10.1007/BF02099937. [DOI] [PubMed] [Google Scholar]
  15. Hanai R., Wada A. The effects of guanine and cytosine variation on dinucleotide frequency and amino acid composition in the human genome. J Mol Evol. 1988;27(4):321–325. doi: 10.1007/BF02101194. [DOI] [PubMed] [Google Scholar]
  16. Hoffmann J. W., Steffen D., Gusella J., Tabin C., Bird S., Cowing D., Weinberg R. A. DNA methylation affecting the expression of murine leukemia proviruses. J Virol. 1982 Oct;44(1):144–157. doi: 10.1128/jvi.44.1.144-157.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. JOSSE J., KAISER A. D., KORNBERG A. Enzymatic synthesis of deoxyribonucleic acid. VIII. Frequencies of nearest neighbor base sequences in deoxyribonucleic acid. J Biol Chem. 1961 Mar;236:864–875. [PubMed] [Google Scholar]
  18. Jones P. A. DNA methylation and cancer. Cancer Res. 1986 Feb;46(2):461–466. [PubMed] [Google Scholar]
  19. Kypr J., Mrázek J., Reich J. Nucleotide composition bias and CpG dinucleotide content in the genomes of HIV and HTLV 1/2. Biochim Biophys Acta. 1989 Dec 22;1009(3):280–282. doi: 10.1016/0167-4781(89)90114-0. [DOI] [PubMed] [Google Scholar]
  20. McClelland M., Ivarie R. Asymmetrical distribution of CpG in an 'average' mammalian gene. Nucleic Acids Res. 1982 Dec 11;10(23):7865–7877. doi: 10.1093/nar/10.23.7865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McClure M. A., Johnson M. S., Feng D. F., Doolittle R. F. Sequence comparisons of retroviral proteins: relative rates of change and general phylogeny. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2469–2473. doi: 10.1073/pnas.85.8.2469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Niwa O., Yokota Y., Ishida H., Sugahara T. Independent mechanisms involved in suppression of the Moloney leukemia virus genome during differentiation of murine teratocarcinoma cells. Cell. 1983 Apr;32(4):1105–1113. doi: 10.1016/0092-8674(83)90294-5. [DOI] [PubMed] [Google Scholar]
  23. Ohno S., Yomo T. Various regulatory sequences are deprived of their uniqueness by the universal rule of TA/CG deficiency and TG/CT excess. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1218–1222. doi: 10.1073/pnas.87.3.1218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Olmsted R. A., Hirsch V. M., Purcell R. H., Johnson P. R. Nucleotide sequence analysis of feline immunodeficiency virus: genome organization and relationship to other lentiviruses. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8088–8092. doi: 10.1073/pnas.86.20.8088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Overbaugh J., Riedel N., Hoover E. A., Mullins J. I. Transduction of endogenous envelope genes by feline leukaemia virus in vitro. Nature. 1988 Apr 21;332(6166):731–734. doi: 10.1038/332731a0. [DOI] [PubMed] [Google Scholar]
  26. Ponta H., Günzburg W. H., Salmons B., Groner B., Herrlich P. Mouse mammary tumour virus: a proviral gene contributes to the understanding of eukaryotic gene expression and mammary tumorigenesis. J Gen Virol. 1985 May;66(Pt 5):931–943. doi: 10.1099/0022-1317-66-5-931. [DOI] [PubMed] [Google Scholar]
  27. Weiss R. A., Mason W. S., Vogt P. K. Genetic recombinants and heterozygotes derived from endogenous and exogenous avian RNA tumor viruses. Virology. 1973 Apr;52(2):535–552. doi: 10.1016/0042-6822(73)90349-8. [DOI] [PubMed] [Google Scholar]
  28. Wolf S. F., Migeon B. R. Clusters of CpG dinucleotides implicated by nuclease hypersensitivity as control elements of housekeeping genes. Nature. 1985 Apr 4;314(6010):467–469. doi: 10.1038/314467a0. [DOI] [PubMed] [Google Scholar]
  29. Yokoyama S., Chung L., Gojobori T. Molecular evolution of the human immunodeficiency and related viruses. Mol Biol Evol. 1988 May;5(3):237–251. doi: 10.1093/oxfordjournals.molbev.a040495. [DOI] [PubMed] [Google Scholar]

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