Chromosome Research

, Volume 13, Issue 5, pp 525–533

The central roles of telomeres and subtelomeres in antigenic variation in African trypanosomes

Article

Abstract

Telomeres and subtelomeres are important to the virulence of a number of pathogens, as they harbour large diverse gene families associated with the maintenance of infection. Evasion of immunity by African trypanosomes involves the differential expression of variant surface glycoproteins (VSGs), which are encoded by a family of >1500 genes and pseudogenes. This silent archive is located subtelomerically and is activated by gene conversion into specialized transcription units, which themselves are subject to silencing by allelic exclusion. Current research addresses the role of telomeres in the conversion and silencing mechanisms and in the diversification of the VSG archive.

Key words

antigenic variation telomere trypanosome VSG 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aline RF, Stuart K (1989) Trypanosoma brucei – conserved sequence organization 3′ to telomeric variant surface glycoprotein genes. Exp Parasitol 68: 57–66.CrossRefPubMedGoogle Scholar
  2. Askree SH, Yehuda T, Smolikov S et al. (2004) A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length. Proc Natl Acad Sci USA 101: 8658–8663.CrossRefPubMedGoogle Scholar
  3. Barry JD, McCulloch R (2001) Antigenic variation in trypanosomes: Enhanced phenotypic variation in a eukaryotic parasite. Adv Parasitol 49: 1–70.PubMedGoogle Scholar
  4. Barry JD, Ginger ML, Burton P, McCulloch R (2003) Why are parasite contingency genes often associated with telomeres? Int J Parasitol 33: 29–45.CrossRefPubMedGoogle Scholar
  5. Becker M, Aitcheson N, Byles E, Wickstead B, Louis E, Rudenko G (2004) Isolation of the repertoire of VSG expression site containing telomeres of Trypanosoma brucei 427 using transformation-associated recombination in yeast. Genome Res 14: 2319–2329.CrossRefPubMedGoogle Scholar
  6. Berberof M, Vanhamme L, Tebabi P et al. (1995) The 3′-terminal region of the messenger RNAs for VSG and procyclin can confer stage specificity to gene expression in Trypanosoma brucei. EMBO J 14: 2925–2934.PubMedGoogle Scholar
  7. Bernards A, Michels PAM, Lincke CR, Borst P (1983) Growth of chromosome ends in multiplying trypanosomes. Nature 303: 592–597.PubMedGoogle Scholar
  8. Berriman M, Hall N, Sheader K et al. (2002) The architecture of variant surface glycoprotein gene expression sites in Trypanosoma brucei. Mol Biochem Parasitol 122: 131–140.CrossRefPubMedGoogle Scholar
  9. Blackburn EH, Challoner PB (1984) Identification of a telomeric DNA sequence in Trypanosoma brucei. Cell 36: 447–457.CrossRefPubMedGoogle Scholar
  10. Borst P, Chaves I (1999) Mono-allelic expression of genes in simple eukaryotes. Trends Genet 15: 95–96.CrossRefGoogle Scholar
  11. Bringaud F, Biteau N, Melville SE et al. (2002) A new, expressed multigene family containing a hot spot for insertion of retroelements is associated with polymorphic subtelomeric regions of Trypanosoma brucei. Eukaryot Cell 1: 137–151.CrossRefPubMedGoogle Scholar
  12. Cano MI (2001) Telomere biology of trypanosomatids: more questions than answers. Trends Parasitol 17: 425–429.PubMedGoogle Scholar
  13. Cano MIN, Dungan JM, Agabian N, Blackburn EH (1999) Telomerase in kinetoplastid parasitic protozoa. Proc Natl Acad Sci USA 96: 3616–3621.CrossRefPubMedGoogle Scholar
  14. Chaves I, Rudenko G, Dirks-Mulder A, Cross M, Borst P (1999) Control of variant surface glycoprotein gene expression sites in Trypanosoma brucei. EMBO J 18: 4846–4855.CrossRefPubMedGoogle Scholar
  15. Chiurillo MA, Cano I, Dasilveira JF, Ramirez JL (1999) Organization of telomeric and sub-telomeric regions of chromosomes from the protozoan parasite Trypanosoma cruzi. Mol Biochem Parasitol 100: 173–183.CrossRefPubMedGoogle Scholar
  16. Chiurillo MA, Beck AE, Devos T, Myler PJ, Stuart K, Ramirez JL (2000) Cloning and characterization of Leishmania donovani telomeres. Exp Parasitol 94: 248–258.CrossRefPubMedGoogle Scholar
  17. Conway C, McCulloch R, Ginger ML, Robinson NP, Browitt A, Barry JD (2002a) Ku is important for telomere maintenance, but not for differential expression of telomeric VSG genes, in African trypanosomes. J Biol Chem 277: 21269–21277.CrossRefPubMedGoogle Scholar
  18. Conway C, Proudfoot C, Burton P, Barry JD, McCulloch R (2002b) Two pathways of homologous recombination in Trypanosoma brucei. Mol Microbiol 45: 1687–1700.CrossRefPubMedGoogle Scholar
  19. De Las Penas A, Pan SJ, Castano I, Alder J, Cregg R, Cormack BP (2003) Virulence-related surface glycoproteins in the yeast pathogen Candida glabrata are encoded in subtelomeric clusters and subject to RAP1- and SIR-dependent transcriptional silencing. Genes Dev 17: 2245–2258.CrossRefPubMedGoogle Scholar
  20. DiPaolo C, Kieft R, Cross M, Sabatini R (2005) Regulation of trypanosome DNA glycosylation by a SWI2/SNF2-like protein. Mol Cell 17: 441–451.CrossRefPubMedGoogle Scholar
  21. Duraisingh MT, Voss TS, Marty AJ et al. (2005) Heterochromatin silencing and locus repositioning linked to regulation of virulence genes in Plasmodium falciparum. Cell 121: 13–24.CrossRefPubMedGoogle Scholar
  22. Eid JE, Sollner-Webb B (1997) ST-2, a telomere and subtelomere duplex and g-strand binding protein activity in Trypanosoma brucei. J Biol Chem 272: 14927–14936.CrossRefPubMedGoogle Scholar
  23. Freitas-Junior LH, Porto RM, Pirrit LA, Schenkman S, Scherf A (1999) Identification of the telomere in Trypanosoma cruzi reveals highly heterogeneous telomere lengths in different parasite strains. Nucleic Acids Res 27: 2451–2456.PubMedGoogle Scholar
  24. Freitas-Junior LH, Hernandez-Rivas R, Ralph SA et al. (2005) Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites. Cell 121: 25–36.CrossRefPubMedGoogle Scholar
  25. Fu GL, Barker DC (1998) Characterisation of Leishmania telomeres reveals unusual telomeric repeats and conserved telomere-associated sequence. Nucleic Acids Res 26: 2161–2167.CrossRefPubMedGoogle Scholar
  26. Garcia-Salcedo JA, Gijon P, Nolan DP, Tebabi P, Pays E (2003) A chromosomal SIR2 homologue with both histone NAD-dependent ADP-ribosyltransferase and deacetylase activities is involved in DNA repair in Trypanosoma brucei. EMBO J 22: 5851–5862.CrossRefPubMedGoogle Scholar
  27. Ghedin E, Bringaud F, Peterson J et al. (2004) Gene synteny and evolution of genome architecture in trypanosomatids. Mol Biochem Parasitol 134: 183–191.CrossRefPubMedGoogle Scholar
  28. Graham SV, Terry S, Barry JD (1999) A structural and transcription pattern for variant surface glycoprotein gene expression sites used in metacyclic stage Trypanosoma brucei. Mol Biochem Parasitol 103: 141–154.CrossRefPubMedGoogle Scholar
  29. Greider CW (1999) Telomeres do d-loop-t-loop. Cell 97: 419–422.CrossRefPubMedGoogle Scholar
  30. Hall N, Berriman M, Lennard NJ et al. (2003) The DNA sequence of chromosome I of an African trypanosome: gene content, chromosome organisation, recombination and polymorphism. Nucleic Acids Res 31: 4864–4873.CrossRefPubMedGoogle Scholar
  31. Hertz-Fowler C, Peacock CS, Wood V et al. (2004) GeneDB: a resource for prokaryotic and eukaryotic organisms. Nucleic Acids Res 32: D339–D343.CrossRefPubMedGoogle Scholar
  32. Horn D (2004) The molecular control of antigenic variation in Trypanosoma brucei. Curr Mol Med 4: 563–576.CrossRefPubMedGoogle Scholar
  33. Horn D, Cross GAM (1997) Position-dependent and promoter-specific regulation of gene expression in Trypanosoma brucei. EMBO J 16: 7422–7431.CrossRefPubMedGoogle Scholar
  34. Horn D, Spence C, Ingram AK (2000) Telomere maintenance and length regulation in Trypanosoma brucei. EMBO J 19: 2332–2339.CrossRefPubMedGoogle Scholar
  35. Janzen CJ, Lander F, Dreesen O, Cross GA (2004) Telomere length regulation and transcriptional silencing in KU80-deficient Trypanosoma brucei. Nucleic Acids Res 32: 6575–6584.CrossRefPubMedGoogle Scholar
  36. Kamper SM, Barbet AF (1992) Surface epitope variation via mosaic gene formation is potential key to long-term survival of Trypanosoma brucei. Mol Biochem Parasitol 53: 33–44.CrossRefPubMedGoogle Scholar
  37. Kazazian HH (2004) Mobile elements: drivers of genome evolution. Science 303: 1626–1632.CrossRefPubMedGoogle Scholar
  38. Lebrun E, Revardel E, Boscheron C, Li R, Gilson E, Fourel G (2001) Protosilencers in Saccharomyces cerevisiae subtelomeric regions. Genetics 158: 167–176.PubMedGoogle Scholar
  39. Lowell JE, Cross GA (2004) A variant histone H3 is enriched at telomeres in Trypanosoma brucei. J Cell Sci 117: 5937–5947.CrossRefPubMedGoogle Scholar
  40. Majumder HK, Boothroyd JC, Weber H (1981) Homologous 3′-terminal regions of mRNAs for surface antigens of different antigenic variants of Trypanosoma brucei. Nucleic Acids Res 9: 4745–4753.PubMedGoogle Scholar
  41. Matthews KR, Shiels PG, Graham SV, Cowan C, Barry JD (1990) Duplicative activation mechanisms of two trypanosome telomeric VSG genes with structurally simple 5′ flanks. Nucleic Acids Res 18: 7219–7227.PubMedGoogle Scholar
  42. McCulloch R, Rudenko G, Borst P (1997) Gene conversions mediating antigenic variation in Trypanosoma brucei can occur in variant surface glycoprotein expression sites lacking 70 base-pair repeat sequences. Mol Cell Biol 17: 833–843.PubMedGoogle Scholar
  43. Melville SE, Leech V, Navarro M, Cross GAM (2000) The molecular karyotype of the megabase chromosomes of Trypanosoma brucei stock 427. Mol Biochem Parasitol 111: 261–273.CrossRefPubMedGoogle Scholar
  44. Munoz DP, Collins K (2004) Biochemical properties of Trypanosoma cruzi telomerase. Nucleic Acids Res 32: 5214–5222.CrossRefPubMedGoogle Scholar
  45. Munoz-Jordan JL, Cross GAM (2001) Telomere shortening and cell cycle arrest in Trypanosoma brucei expressing human telomeric repeat factor TRF1. Mol Biochem Parasitol 114: 169–181.CrossRefPubMedGoogle Scholar
  46. Munoz-Jordan JL, Cross GAM, de Lange T, Griffith JD (2001) T-loops at trypanosome telomeres. EMBO J 20: 579–588.PubMedGoogle Scholar
  47. Navarro M, Gull K (2001) A pol I transcriptional body associated with VSG monoallelic expression in Trypanosoma brucei. Nature 414: 759–763.PubMedGoogle Scholar
  48. Pays E, Laurent M, Delinte K, Van Meirvenne N, Steinert M (1983) Differential size variations between transcriptionally active and inactive telomeres of Trypanosoma brucei. Nucleic Acids Res 11: 8137–8147.PubMedGoogle Scholar
  49. Pays E, Vanhamme L, Berberof M (1994) Genetic controls for the expression of surface antigens in African trypanosomes. Annu Rev Microbiol 48: 25–52.PubMedGoogle Scholar
  50. Pays E, Lips S, Nolan D, Vanhamme L, Perez-Morga D (2001) The VSG expression sites of Trypanosoma brucei: multipurpose tools for the adaptation of the parasite to mammalian hosts. Mol Biochem Parasitol 114: 1–16.CrossRefPubMedGoogle Scholar
  51. Pays E, Vanhamme L, Perez-Morga D (2004) Antigenic variation in Trypanosoma brucei: facts, challenges and mysteries. Curr Opin Microbiol 7: 369–374.PubMedGoogle Scholar
  52. Perez-Morga D, Amiguet-Vercher A, Vermijlen D, Pays E (2001) Organization of telomeres during the cell and life cycles of Trypanosoma brucei. J Eukaryot Microbiol 48: 221–226.CrossRefPubMedGoogle Scholar
  53. Ricchetti M, Dujon B, Fairhead C (2003) Distance from the chromosome end determines the efficiency of double strand break repair in subtelomeres of haploid yeast. J Mol Biol 328: 847–862.CrossRefPubMedGoogle Scholar
  54. Robinson NP, Burman N, Melville SE, Barry JD (1999) Predominance of duplicative VSG gene conversion in antigenic variation in African trypanosomes. Mol Cell Biol 19: 5839–5846.PubMedGoogle Scholar
  55. Robinson NP, McCulloch R, Conway C, Browitt A, Barry JD (2002) Inactivation of Mre11 does not affect VSG gene duplication mediated by homologous recombination in Trypanosoma brucei. J Biol Chem 277: 26185–26193.CrossRefPubMedGoogle Scholar
  56. Sabatini R, Meeuwenoord N, Van Boom JH, Borst P (2002) Recognition of base J in duplex DNA by J-binding protein. J Biol Chem 277: 958–966.CrossRefPubMedGoogle Scholar
  57. Shah JS, Young JR, Kimmel BE, Iams KP, Williams RO (1987) The 5′ flanking sequence of a Trypanosoma brucei variable surface glycoprotein gene. Mol Biochem Parasitol 24: 163–174.CrossRefPubMedGoogle Scholar
  58. Sheader K, Berberof M, Isobe T, Borst P, Rudenko G (2003) Delineation of the regulated Variant Surface Glycoprotein gene expression site domain of Trypanosoma brucei. Mol Biochem Parasitol 128: 147–156.CrossRefPubMedGoogle Scholar
  59. Smogorzewska A, de Lange T (2004) Regulation of telomerase by telomeric proteins. Annu Rev Biochem 73: 177–208.Google Scholar
  60. Tan KS, Leal ST, Cross GA (2002) Trypanosoma brucei MRE11 is non-essential but influences growth, homologous recombination and DNA double-strand break repair. Mol Biochem Parasitol 125: 11–21.CrossRefPubMedGoogle Scholar
  61. Thon G, Baltz T, Giroud C, Eisen H (1990) Trypanosome variable surface glycoproteins: composite genes and order of expression. Genes Dev 9: 1374–1383.Google Scholar
  62. Urakawa T, Eshita Y, Majiwa PAO (1997) The primary structure of Trypanosoma (Nannomonas) congolense variant surface glycoproteins. Exp Parasitol 85: 215–224.CrossRefPubMedGoogle Scholar
  63. Van der Ploeg LHT, Liu AYC, Borst P (1984) Structure of the growing telomeres of trypanosomes. Cell 36: 459–468.CrossRefPubMedGoogle Scholar
  64. Vanhamme L, Poelvoorde P, Pays A, Tebabi P, Xong HV, Pays E (2000) Differential RNA elongation controls the variant surface glycoprotein gene expression sites of Trypanosoma brucei. Mol Microbiol 36: 328–340.CrossRefPubMedGoogle Scholar
  65. van Leeuwen F, Taylor MC, Mondragon A et al. (1998) β-D-glucosylhydroxymethyluracil is a conserved DNA modification in kinetoplastid protozoans and is abundant in their telomeres. Proc Natl Acad Sci USA 95: 2366–2371.CrossRefPubMedGoogle Scholar
  66. Weiden M, Osheim YN, Beyer AL, Van der Ploeg LHT (1991) Chromosome structure–DNA nucleotide sequence elements of a subset of the minichromosomes of the protozoan Trypanosoma brucei. Mol Cell Biol 11: 3823–3834.PubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  1. 1.London School of Hygiene & Tropical MedicineLondonUK
  2. 2.The Anderson CollegeUniversity of GlasgowGlasgowUK

Personalised recommendations