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. 1983 Mar;45(3):941–949. doi: 10.1128/jvi.45.3.941-949.1983

Further Evidence for the Protein Coding Potential of the Mouse Mammary Tumor Virus Long Terminal Repeat: Nucleotide Sequence of an Endogenous Proviral Long Terminal Repeat

Lawrence A Donehower 1, Barbara Fleurdelys 1, Gordon L Hager 1
PMCID: PMC256499  PMID: 6300464

Abstract

The 3′ half of an endogenous mouse mammary tumor virus from a C3H mouse was cloned in the Charon 4A vector phage. A comparison of the proviral clone with previously published endogenous mouse mammary tumor virus restriction maps identified it as endogenous unit II (J. Cohen and H. Varmus, Nature [London] 278:418-423, 1979), which is present in all inbred mouse strains derived from the original Bagg albino × DBA cross. The nucleotide sequence of the unit II long terminal redundancy (LTR) was determined and compared with the sequence previously determined for the exogenous C3H virus LTR (Donehower et al., J. Virol. 37:226-238, 1981). Virtually all sequence differences between the two LTRs were base substitutions. The total amount of sequence divergence was 6.6%. The large open reading frame reported previously in the exogenous LTR was preserved in the endogenous LTR. In addition, the pattern of sequence divergence was highly nonrandom with respect to the putative amino acid codons of the two open reading frames. Most of the base substitutions in this region resulted in silent or conservative amino acid codon changes. The nonrandom divergence pattern indicates that selective forces are operating on this segment of DNA and argues that the putative protein is functional in the life cycle of mouse mammary tumor virus. Possible roles for the protein and its mode of expression are discussed.

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Selected References

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

  1. Bentvelzen P., Daams J. H. Hereditary infections with mammary tumor viruses in mice. J Natl Cancer Inst. 1969 Nov;43(5):1025–1035. [PubMed] [Google Scholar]
  2. Benz E. W., Jr, Wydro R. M., Nadal-Ginard B., Dina D. Moloney murine sarcoma proviral DNA is a transcriptional unit. Nature. 1980 Dec 25;288(5792):665–669. doi: 10.1038/288665a0. [DOI] [PubMed] [Google Scholar]
  3. Bittner J. J. SOME POSSIBLE EFFECTS OF NURSING ON THE MAMMARY GLAND TUMOR INCIDENCE IN MICE. Science. 1936 Aug 14;84(2172):162–162. doi: 10.1126/science.84.2172.162. [DOI] [PubMed] [Google Scholar]
  4. Coffin J. M., Champion M., Chabot F. Nucleotide sequence relationships between the genomes of an endogenous and an exogenous avian tumor virus. J Virol. 1978 Dec;28(3):972–991. doi: 10.1128/jvi.28.3.972-991.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coffin J. M., Tsichlis P. N., Barker C. S., Voynow S., Robinson H. L. Variation in avian retrovirus genomes. Ann N Y Acad Sci. 1980;354:410–425. doi: 10.1111/j.1749-6632.1980.tb27982.x. [DOI] [PubMed] [Google Scholar]
  6. Cohen J. C., Majors J. E., Varmus H. E. Organization of mouse mammary tumor virus-specific DNA endogenous to BALB/c mice. J Virol. 1979 Nov;32(2):483–496. doi: 10.1128/jvi.32.2.483-496.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cohen J. C. Methylation of milk-borne and genetically transmitted mouse mammary tumor virus proviral DNA. Cell. 1980 Mar;19(3):653–662. doi: 10.1016/s0092-8674(80)80042-0. [DOI] [PubMed] [Google Scholar]
  8. Cohen J. C., Shank P. R., Morris V. L., Cardiff R., Varmus H. E. Integration of the DNA of mouse mammary tumor virus in virus-infected normal and neoplastic tissue of the mouse. Cell. 1979 Feb;16(2):333–345. doi: 10.1016/0092-8674(79)90010-2. [DOI] [PubMed] [Google Scholar]
  9. Cohen J. C., Varmus H. E. Endogenous mammary tumour virus DNA varies among wild mice and segregates during inbreeding. Nature. 1979 Mar 29;278(5703):418–423. doi: 10.1038/278418a0. [DOI] [PubMed] [Google Scholar]
  10. Dickson C., Peters G. Protein-coding potential of mouse mammary tumor virus genome RNA as examined by in vitro translation. J Virol. 1981 Jan;37(1):36–47. doi: 10.1128/jvi.37.1.36-47.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dickson C., Smith R., Peters G. In vitro synthesis of polypeptides encoded by the long terminal repeat region of mouse mammary tumour virus DNA. Nature. 1981 Jun 11;291(5815):511–513. doi: 10.1038/291511a0. [DOI] [PubMed] [Google Scholar]
  12. Donehower L. A., Andre J., Berard D. S., Wolford R. G., Hager G. L. Construction and characterization of molecular clones containing integrated mouse mammary tumor virus sequences. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):1153–1159. doi: 10.1101/sqb.1980.044.01.124. [DOI] [PubMed] [Google Scholar]
  13. Donehower L. A., Huang A. L., Hager G. L. Regulatory and coding potential of the mouse mammary tumor virus long terminal redundancy. J Virol. 1981 Jan;37(1):226–238. doi: 10.1128/jvi.37.1.226-238.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Efstratiadis A., Posakony J. W., Maniatis T., Lawn R. M., O'Connell C., Spritz R. A., DeRiel J. K., Forget B. G., Weissman S. M., Slightom J. L. The structure and evolution of the human beta-globin gene family. Cell. 1980 Oct;21(3):653–668. doi: 10.1016/0092-8674(80)90429-8. [DOI] [PubMed] [Google Scholar]
  15. Groner B., Hynes N. E. Number and location of mouse mammary tumor virus proviral DNA in mouse DNA of normal tissue and of mammary tumors. J Virol. 1980 Mar;33(3):1013–1025. doi: 10.1128/jvi.33.3.1013-1025.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hishinuma F., DeBona P. J., Astrin S., Skalka A. M. Nucleotide sequence of acceptor site and termini of integrated avian endogenous provirus ev1: integration creates a 6 bp repeat of host DNA. Cell. 1981 Jan;23(1):155–164. doi: 10.1016/0092-8674(81)90280-4. [DOI] [PubMed] [Google Scholar]
  17. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  18. Michalides R., van Deemter L., Nuss R. R., van Nie R. Identification of the Mtv-2 gene responsible for the early appearance of mammary tumors in the GR mouse by nucleic acid hybridization. Proc Natl Acad Sci U S A. 1978 May;75(5):2368–2372. doi: 10.1073/pnas.75.5.2368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Michalides R., van Nie R., Nusse R., Hynes N. E., Groner B. Mammary tumor induction loci in GR and DBAf mice contain one provirus of the mouse mammary tumor virus. Cell. 1981 Jan;23(1):165–173. doi: 10.1016/0092-8674(81)90281-6. [DOI] [PubMed] [Google Scholar]
  20. Morris V. L., Medeiros E., Ringold G. M., Bishop J. M., Varmus H. E. Comparison of mouse mammary tumor virus-specific DNA in inbred, wild and Asian mice, and in tumors and normal organs from inbred mice. J Mol Biol. 1977 Jul;114(1):73–91. doi: 10.1016/0022-2836(77)90284-4. [DOI] [PubMed] [Google Scholar]
  21. Owens R. B., Hackett A. J. Tissue culture studies of mouse mammary tumor cells and associated viruses. J Natl Cancer Inst. 1972 Nov;49(5):1321–1332. [PubMed] [Google Scholar]
  22. Parks W. P., Hubbell E. S., Goldberg R. J., O'Neill F. J., Scolnick E. M. High frequency variation in mammary tumor virus expression in cell culture. Cell. 1976 May;8(1):87–93. doi: 10.1016/0092-8674(76)90189-6. [DOI] [PubMed] [Google Scholar]
  23. Ringold G. M., Shank P. R., Varmus H. E., Ring J., Yamamoto K. R. Integration and transcription of mouse mammary tumor virus DNA in rat hepatoma cells. Proc Natl Acad Sci U S A. 1979 Feb;76(2):665–669. doi: 10.1073/pnas.76.2.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sanger F., Coulson A. R. The use of thin acrylamide gels for DNA sequencing. FEBS Lett. 1978 Mar 1;87(1):107–110. doi: 10.1016/0014-5793(78)80145-8. [DOI] [PubMed] [Google Scholar]
  25. Sen G. C., Racevskis J., Sarkar N. H. Synthesis of murine mammary tumor viral proteins in vitro. J Virol. 1981 Mar;37(3):963–975. doi: 10.1128/jvi.37.3.963-975.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shank P. R., Cohen J. C., Varmus H. E., Yamamoto K. R., Ringold G. M. Mapping of linear and circular forms of mouse mammary tumor virus DNA with restriction endonucleases: evidence for a large specific deletion occurring at high frequency during circularization. Proc Natl Acad Sci U S A. 1978 May;75(5):2112–2116. doi: 10.1073/pnas.75.5.2112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shimotohno K., Mizutani S., Temin H. M. Sequence of retrovirus provirus resembles that of bacterial transposable elements. Nature. 1980 Jun 19;285(5766):550–554. doi: 10.1038/285550a0. [DOI] [PubMed] [Google Scholar]
  28. Staats J. Standardized nomenclature for inbred strains of mice: sixth listing. Cancer Res. 1976 Dec;36(12):4333–4377. [PubMed] [Google Scholar]
  29. Sutcliffe J. G., Shinnick T. M., Verma I. M., Lerner R. A. Nucleotide sequence of Moloney leukemia virus: 3' end reveals details of replications, analogy to bacterial transposons, and an unexpected gene. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3302–3306. doi: 10.1073/pnas.77.6.3302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Swanstrom R., DeLorbe W. J., Bishop J. M., Varmus H. E. Nucleotide sequence of cloned unintegrated avian sarcoma virus DNA: viral DNA contains direct and inverted repeats similar to those in transposable elements. Proc Natl Acad Sci U S A. 1981 Jan;78(1):124–128. doi: 10.1073/pnas.78.1.124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tsichlis P. N., Coffin J. M. Recombination between the defective component of an acute leukemia virus and Rous associated virus O, an endogenous virus of chickens. Proc Natl Acad Sci U S A. 1979 Jun;76(6):3001–3005. doi: 10.1073/pnas.76.6.3001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Van Beveren C., Goddard J. G., Berns A., Verma I. M. Structure of Moloney murine leukemia viral DNA: nucleotide sequence of the 5' long terminal repeat and adjacent cellular sequences. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3307–3311. doi: 10.1073/pnas.77.6.3307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Van Nie R., Verstraeten A. A., De Moes J. Genetic transmission of mammary tumour virus by GR mice. Int J Cancer. 1977 Mar 15;19(3):383–390. doi: 10.1002/ijc.2910190316. [DOI] [PubMed] [Google Scholar]
  34. Yamamoto K. R., Stallcup M. R., Ring J., Ringold G. M. Mammary tumor virus DNA: a glucocorticoid-responsive transposable element. Cold Spring Harb Symp Quant Biol. 1978;42(Pt 2):625–638. doi: 10.1101/sqb.1978.042.01.065. [DOI] [PubMed] [Google Scholar]
  35. van Nie R., Verstraeten A. A. Studies of genetic transmission of mammary tumour virus by C3Hf mice. Int J Cancer. 1975 Dec 15;16(6):922–931. doi: 10.1002/ijc.2910160606. [DOI] [PubMed] [Google Scholar]

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