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. 1990 Dec 25;18(24):7219–7227. doi: 10.1093/nar/18.24.7219

Duplicative activation mechanisms of two trypanosome telomeric VSG genes with structurally simple 5' flanks.

K R Matthews 1, P G Shiels 1, S V Graham 1, C Cowan 1, J D Barry 1
PMCID: PMC332856  PMID: 2175429

Abstract

In the mammalian bloodstream, African trypanosomes express variant surface glycoprotein (VSG) genes from a family of long and complex telomeric expression sites. VSG switching generally occurs by the duplication of different VSG genes into these sites by gene conversion involving a series of 70 base pair (70bp) repeats in the 5' flank. In contrast, when VSG is first synthesised by trypanosomes in the tsetse fly at the metacyclic stage, a separate set of telomeric expression sites is activated. These latter telomeres appear not to act as recipients in gene conversion. We have found that the structure of two such expression sites is simple, with very short 70bp repeat regions and very little other sequence in common with bloodstream expression sites. However, the two telomeres readily act as donors in VSG gene conversion in the bloodstream and we show for one a consistent association of the conversion 5' end point with the short 70bp repeat region. These findings help explain why a very predictable set of VSGs is expressed in the tsetse fly and have implications for VSG gene conversion mechanisms.

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Selected References

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

  1. Alexandre S., Guyaux M., Murphy N. B., Coquelet H., Pays A., Steinert M., Pays E. Putative genes of a variant-specific antigen gene transcription unit in Trypanosoma brucei. Mol Cell Biol. 1988 Jun;8(6):2367–2378. doi: 10.1128/mcb.8.6.2367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aline R. F., Jr, Scholler J. K., Nelson R. G., Agabian N., Stuart K. Preferential activation of telomeric variant surface glycoprotein genes in Trypanosoma brucei. Mol Biochem Parasitol. 1985 Dec;17(3):311–320. doi: 10.1016/0166-6851(85)90005-2. [DOI] [PubMed] [Google Scholar]
  3. Aline R., Jr, MacDonald G., Brown E., Allison J., Myler P., Rothwell V., Stuart K. (TAA)n within sequences flanking several intrachromosomal variant surface glycoprotein genes in Trypanosoma brucei. Nucleic Acids Res. 1985 May 10;13(9):3161–3177. doi: 10.1093/nar/13.9.3161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barry J. D., Crowe J. S., Vickerman K. Instability of the Trypanosoma brucei rhodesiense metacyclic variable antigen repertoire. Nature. 1983 Dec 15;306(5944):699–701. doi: 10.1038/306699a0. [DOI] [PubMed] [Google Scholar]
  5. Bernards A., De Lange T., Michels P. A., Liu A. Y., Huisman M. J., Borst P. Two modes of activation of a single surface antigen gene of Trypanosoma brucei. Cell. 1984 Jan;36(1):163–170. doi: 10.1016/0092-8674(84)90085-0. [DOI] [PubMed] [Google Scholar]
  6. Bernards A., Kooter J. M., Borst P. Structure and transcription of a telomeric surface antigen gene of Trypanosoma brucei. Mol Cell Biol. 1985 Mar;5(3):545–553. doi: 10.1128/mcb.5.3.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bernards A., Van der Ploeg L. H., Frasch A. C., Borst P., Boothroyd J. C., Coleman S., Cross G. A. Activation of trypanosome surface glycoprotein genes involves a duplication-transposition leading to an altered 3' end. Cell. 1981 Dec;27(3 Pt 2):497–505. doi: 10.1016/0092-8674(81)90391-3. [DOI] [PubMed] [Google Scholar]
  8. Borst P. Discontinuous transcription and antigenic variation in trypanosomes. Annu Rev Biochem. 1986;55:701–732. doi: 10.1146/annurev.bi.55.070186.003413. [DOI] [PubMed] [Google Scholar]
  9. Campbell D. A., van Bree M. P., Boothroyd J. C. The 5'-limit of transposition and upstream barren region of a trypanosome VSG gene: tandem 76 base-pair repeats flanking (TAA)90. Nucleic Acids Res. 1984 Mar 26;12(6):2759–2774. doi: 10.1093/nar/12.6.2759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cornelissen A. W., Bakkeren G. A., Barry J. D., Michels P. A., Borst P. Characteristics of trypanosome variant antigen genes active in the tsetse fly. Nucleic Acids Res. 1985 Jul 11;13(13):4661–4676. doi: 10.1093/nar/13.13.4661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Crowe J. S., Barry J. D., Luckins A. G., Ross C. A., Vickerman K. All metacyclic variable antigen types of Trypanosoma congolense identified using monoclonal antibodies. Nature. 1983 Nov 24;306(5941):389–391. doi: 10.1038/306389a0. [DOI] [PubMed] [Google Scholar]
  12. Cully D. F., Ip H. S., Cross G. A. Coordinate transcription of variant surface glycoprotein genes and an expression site associated gene family in Trypanosoma brucei. Cell. 1985 Aug;42(1):173–182. doi: 10.1016/s0092-8674(85)80113-6. [DOI] [PubMed] [Google Scholar]
  13. Delauw M. F., Laurent M., Paindavoine P., Aerts D., Pays E., Le Ray D., Steinert M. Characterization of genes coding for two major metacyclic surface antigens in Trypanosoma brucei. Mol Biochem Parasitol. 1987 Feb;23(1):9–17. doi: 10.1016/0166-6851(87)90181-2. [DOI] [PubMed] [Google Scholar]
  14. Esser K. M., Schoenbechler M. J. Expression of two variant surface glycoproteins on individual African trypanosomes during antigen switching. Science. 1985 Jul 12;229(4709):190–193. doi: 10.1126/science.3892689. [DOI] [PubMed] [Google Scholar]
  15. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  16. Fincham J. R., Oliver P. Meiosis: initiation of recombination. Nature. 1989 Mar 2;338(6210):14–15. doi: 10.1038/338014a0. [DOI] [PubMed] [Google Scholar]
  17. Florent I., Baltz T., Raibaud A., Eisen H. On the role of repeated sequences 5' to variant surface glycoprotein genes in African trypanosomes. Gene. 1987;53(1):55–62. doi: 10.1016/0378-1119(87)90092-8. [DOI] [PubMed] [Google Scholar]
  18. Johnson P. J., Kooter J. M., Borst P. Inactivation of transcription by UV irradiation of T. brucei provides evidence for a multicistronic transcription unit including a VSG gene. Cell. 1987 Oct 23;51(2):273–281. doi: 10.1016/0092-8674(87)90154-1. [DOI] [PubMed] [Google Scholar]
  19. Kimmel B. E., ole-MoiYoi O. K., Young J. R. Ingi, a 5.2-kb dispersed sequence element from Trypanosoma brucei that carries half of a smaller mobile element at either end and has homology with mammalian LINEs. Mol Cell Biol. 1987 Apr;7(4):1465–1475. doi: 10.1128/mcb.7.4.1465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kooter J. M., Winter A. J., de Oliveira C., Wagter R., Borst P. Boundaries of telomere conversion in Trypanosoma brucei. Gene. 1988 Sep 15;69(1):1–11. doi: 10.1016/0378-1119(88)90372-1. [DOI] [PubMed] [Google Scholar]
  21. Kooter J. M., van der Spek H. J., Wagter R., d'Oliveira C. E., van der Hoeven F., Johnson P. J., Borst P. The anatomy and transcription of a telomeric expression site for variant-specific surface antigens in T. brucei. Cell. 1987 Oct 23;51(2):261–272. doi: 10.1016/0092-8674(87)90153-x. [DOI] [PubMed] [Google Scholar]
  22. Lee M. G., Van der Ploeg L. H. Frequent independent duplicative transpositions activate a single VSG gene. Mol Cell Biol. 1987 Jan;7(1):357–364. doi: 10.1128/mcb.7.1.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lenardo M. J., Esser K. M., Moon A. M., Van der Ploeg L. H., Donelson J. E. Metacyclic variant surface glycoprotein genes of Trypanosoma brucei subsp. rhodesiense are activated in situ, and their expression is transcriptionally regulated. Mol Cell Biol. 1986 Jun;6(6):1991–1997. doi: 10.1128/mcb.6.6.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lenardo M. J., Rice-Ficht A. C., Kelly G., Esser K. M., Donelson J. E. Characterization of the genes specifying two metacyclic variable antigen types in Trypanosoma brucei rhodesiense. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6642–6646. doi: 10.1073/pnas.81.21.6642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Liu A. Y., Van der Ploeg L. H., Rijsewijk F. A., Borst P. The transposition unit of variant surface glycoprotein gene 118 of Trypanosoma brucei. Presence of repeated elements at its border and absence of promoter-associated sequences. J Mol Biol. 1983 Jun 15;167(1):57–75. doi: 10.1016/s0022-2836(83)80034-5. [DOI] [PubMed] [Google Scholar]
  26. Michels P. A., Van der Ploeg L. H., Liu A. Y., Borst P. The inactivation and reactivation of an expression-linked gene copy for a variant surface glycoprotein in Trypanosoma brucei. EMBO J. 1984 Jun;3(6):1345–1351. doi: 10.1002/j.1460-2075.1984.tb01975.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Murphy N. B., Pays A., Tebabi P., Coquelet H., Guyaux M., Steinert M., Pays E. Trypanosoma brucei repeated element with unusual structural and transcriptional properties. J Mol Biol. 1987 Jun 20;195(4):855–871. doi: 10.1016/0022-2836(87)90490-6. [DOI] [PubMed] [Google Scholar]
  28. Pays E., Guyaux M., Aerts D., Van Meirvenne N., Steinert M. Telomeric reciprocal recombination as a possible mechanism for antigenic variation in trypanosomes. Nature. 1985 Aug 8;316(6028):562–564. doi: 10.1038/316562a0. [DOI] [PubMed] [Google Scholar]
  29. Pays E., Steinert M. Control of antigen gene expression in African trypanosomes. Annu Rev Genet. 1988;22:107–126. doi: 10.1146/annurev.ge.22.120188.000543. [DOI] [PubMed] [Google Scholar]
  30. Pays E., Tebabi P., Pays A., Coquelet H., Revelard P., Salmon D., Steinert M. The genes and transcripts of an antigen gene expression site from T. brucei. Cell. 1989 Jun 2;57(5):835–845. doi: 10.1016/0092-8674(89)90798-8. [DOI] [PubMed] [Google Scholar]
  31. Pluta A. F., Zakian V. A. Recombination occurs during telomere formation in yeast. Nature. 1989 Feb 2;337(6206):429–433. doi: 10.1038/337429a0. [DOI] [PubMed] [Google Scholar]
  32. Shah J. S., Young J. R., Kimmel B. E., Iams K. P., Williams R. O. The 5' flanking sequence of a Trypanosoma brucei variable surface glycoprotein gene. Mol Biochem Parasitol. 1987 Jun;24(2):163–174. doi: 10.1016/0166-6851(87)90103-4. [DOI] [PubMed] [Google Scholar]
  33. Son H. J., Cook G. A., Hall T., Donelson J. E. Expression site associated genes of Trypanosoma brucei rhodesiense. Mol Biochem Parasitol. 1989 Feb;33(1):59–66. doi: 10.1016/0166-6851(89)90042-x. [DOI] [PubMed] [Google Scholar]
  34. Swinkels B. W., Gibson W. C., Osinga K. A., Kramer R., Veeneman G. H., van Boom J. H., Borst P. Characterization of the gene for the microbody (glycosomal) triosephosphate isomerase of Trypanosoma brucei. EMBO J. 1986 Jun;5(6):1291–1298. doi: 10.1002/j.1460-2075.1986.tb04358.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Timmers H. T., de Lange T., Kooter J. M., Borst P. Coincident multiple activations of the same surface antigen gene in Trypanosoma brucei. J Mol Biol. 1987 Mar 5;194(1):81–90. doi: 10.1016/0022-2836(87)90717-0. [DOI] [PubMed] [Google Scholar]
  36. Turner C. M., Barry J. D. High frequency of antigenic variation in Trypanosoma brucei rhodesiense infections. Parasitology. 1989 Aug;99(Pt 1):67–75. doi: 10.1017/s0031182000061035. [DOI] [PubMed] [Google Scholar]
  37. Turner C. M., Barry J. D., Vickerman K. Independent expression of the metacyclic and bloodstream variable antigen repertoires of Trypanosoma brucei rhodesiense. Parasitology. 1986 Feb;92(Pt 1):67–73. doi: 10.1017/s0031182000063459. [DOI] [PubMed] [Google Scholar]
  38. Van der Ploeg L. H., Valerio D., De Lange T., Bernards A., Borst P., Grosveld F. G. An analysis of cosmid clones of nuclear DNA from Trypanosoma brucei shows that the genes for variant surface glycoproteins are clustered in the genome. Nucleic Acids Res. 1982 Oct 11;10(19):5905–5923. doi: 10.1093/nar/10.19.5905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Vickerman K. Developmental cycles and biology of pathogenic trypanosomes. Br Med Bull. 1985 Apr;41(2):105–114. doi: 10.1093/oxfordjournals.bmb.a072036. [DOI] [PubMed] [Google Scholar]
  40. Wang S. S., Zakian V. A. Telomere-telomere recombination provides an express pathway for telomere acquisition. Nature. 1990 May 31;345(6274):456–458. doi: 10.1038/345456a0. [DOI] [PubMed] [Google Scholar]

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