1887

Chapter 40 : Antigenic Variation in Eukaryotic Parasites

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in
Zoomout

Antigenic Variation in Eukaryotic Parasites, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817954/9781555812096_Chap40-1.gif /docserver/preview/fulltext/10.1128/9781555817954/9781555812096_Chap40-2.gif

Abstract:

Organisms with complex genomes cannot afford imprecise genome replication and have to find more sophisticated ways to vary their antigens. This chapter is restricted to antigenic variation in pathogenic protozoa and fungi, and will only describe antigenic variation in four organisms: , , , and . Most of the available evidence suggests, however, that DNA rearrangements are not involved in silencing or in situ switches. This chapter briefly touches on this topic of reversible allelic exclusion between expression sites. The simplicity of the antigenic variation strategy is only apparent, however. The author, limits the discussion to a brief summary of the gene family to allow a comparison with antigenic variation in the other parasites discussed in this chapter. A model showing how reciprocal recombination between the UCS and telomeric MSG genes results in antigenic variation is shown. A complication in the study of Giardia antigenic variation is the polyploidy of its nuclear DNA. The spectacular bacterial pathogens, exemplified by and species, set the tone, and the African trypanosomes appeared to confirm the idea that real antigenic variation requires real DNA rearrangements. DNA rearrangements require enzymes for cutting and joining DNA, and a systematic disruption of the genes for each of these enzymes, as initiated by McCulloch and Barry in trypanosomes, should eventually give us a complete overview of the DNA recombination pathways involved in antigenic variation.

Citation: Borst P. 2002. Antigenic Variation in Eukaryotic Parasites, p 953-971. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch40

Key Concept Ranking

RNA Polymerase I
0.50268817
Integral Membrane Proteins
0.40753657
Pulsed-Field Gel Electrophoresis
0.40753657
0.50268817
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1
Figure 1

Life cycle of the African trypanosome, , showing some of the major life cycle stages. The short stumpy trypomastigote form is preadapted to the tsetse fly and does not multiply. The long slender trypomastigote can be grown in serum-based culture media; the procyclic trypomastigote form can be grown in defined simple media. Reprinted from reference 20 with permission.

Citation: Borst P. 2002. Antigenic Variation in Eukaryotic Parasites, p 953-971. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch40
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

A schematic representation of the cell surface of bloodstream form of , showing a VSG dimer (15, 23), a Tf receptor molecule ( ), which is only present in the flagellar pocket, and a hexose transporter (THT) molecule ( ). For size comparison, a Tf molecule (upper left) and an immunoglobulin (Ig) G antibody molecule (upper right) are shown. The dimensions of the VSG dimer are based on the crystal structure of the N-terminal domain of the protein ( ). The VSG is attached to the glycosyl phosphatidyl inositol anchor via its C-terminal region; the crystal structure of this region is not yet known. The Tf receptor structure is based on its homology with the VSG dimer ( ) (see text). The hexose transporter structure is not based on any solid structural information but is derived from a hypothetical model ( ) of GLUT1. Modified from reference ( ) and reproduced from reference 20 with permission.

Citation: Borst P. 2002. Antigenic Variation in Eukaryotic Parasites, p 953-971. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch40
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

VSG gene expression site of . The standard bloodstream form expression site is modeled after that in reference 85. The flag is the promoter, and the broken line is the primary transcript. ESAGs, expression site-associated genes; rep., repeats. The metacyclic expression site is modeled after that in references 9 and 84. The end of the primary transcript of both expression sites has not been determined and may be further downstream.

Citation: Borst P. 2002. Antigenic Variation in Eukaryotic Parasites, p 953-971. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch40
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5
Figure 5

Donors and acceptor in the duplicative transposition of VSG genes. The acceptor site is identical to that in Fig. 3 , but the elements important for VSG gene transposition are highlighted and slightly enlarged to make them better visible. The overall size of the expression site from promoter down to the telomere tip may vary in size between about 45 and 65 kb ( ), although exceptional sites may be shorter ( ); the 70-bp imperfect repeats may vary at least between 5 and 20 kb ( ); and the (GGGTTA) repeats may grow to at least 20 kb ( ). See text for further details.

Citation: Borst P. 2002. Antigenic Variation in Eukaryotic Parasites, p 953-971. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch40
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

The major mechanisms of VSG switching in . The thick lines represent the so-called 221 VSG expression site, with the flag indicating a promoter, the black box indicating the 221 VSG gene, and the white box indicating a new telomeric VSG gene (VSG gene X). Y and Z are other chromosome-internal VSG genes. The hygromycin resistance gene introduced behind the promoter of the 221 expression site ( Fig. 3 ) is indicated by a hatched box. The dashed line with an arrow indicates the direction of transcription. The figure illustrates how the different mechanisms can be distinguished, by using an expression site marked with a resistance gene. The gene is actively transcribed following the switch in all mechanisms, with the exception of the in situ switch. In gene conversion mechanisms the 221 VSG gene (the only copy of this gene in the genome of the 427 stock of ) is lost. In the reciprocal translocation the 221 VSG gene moves to another chromosome. Reprinted from reference 22 with permission.

Citation: Borst P. 2002. Antigenic Variation in Eukaryotic Parasites, p 953-971. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch40
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6
Figure 6

Models of the installation of MSG sequences at the expression site of . (A) The structure of a telomeric expression site locus is depicted as in f. sp. . This locus starts with exon I of the UCS (stippled rectangle), followed by an intron (line), exon II (stippled rectangle), the CRJE (hatched rectangle), and the MSG gene (gray rectangle). The expression site locus is presumably structured the same way in f. sp. , the MSG gene at the expression site can be changed by recombination at any of three locations: (i) between two CRJEs; (ii) within MSG open-reading frames; or (iii) between two copies of exon II (in cases in which the donor MSG gene has a copy of exon II). By contrast, donor MSGs in f. sp. lack exon II and, therefore, lack pathway 3. (B) Outcomes of switching. Reprinted from reference 95 with permission.

Citation: Borst P. 2002. Antigenic Variation in Eukaryotic Parasites, p 953-971. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch40
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555817954.chap40
1. Adam, R. D. 2000. The Giardia lamblia genome. Int. J. Parasitol. 30: 475 484.
2. Agur, Z. 1992. Mathematical models for African trypanosomiasis. Parasitol. Today 8: 128 129.
3. Agur, Z.,, D. Abiri,, and L. H. Van der Ploeg. 1989. Ordered appearance of antigenic variants of African trypanosomes explained in a mathematical model based on a stochastic switch process and immune-selection against putative switch intermediates. Proc. Natl. Acad. Sci. USA 86: 9626 9630.
4. Alarcon, C. M.,, H. Jin Son,, T. Hall,, and J. E. Donelson. 1994. A monocistronic transcript for a trypanosome variant surface glycoprotein. Mol. Cell. Biol. 14: 5579 5591.
5. Al-Khedery, B.,, J. W. Barnwell,, and M. R. Galinski. 1999. Antigenic variation in malaria: a 3′genomic alteration associated with the expression of a P. knowlesi variant antigen. Mol. Cell 3: 131 141.
6. Ansorge, I.,, D. Steverding,, S. Melville,, C. Hartmann,, and C. Clayton. 1999. Transcription of ‘inactive’ expression sites in African trypanosomes leads to expression of multiple transferrin receptor RNAs in bloodstream forms. Mol. Biochem. Parasitol. 101: 81 94.
7. Barrett, M. P.,, E. Tetaud,, A. Seyfang,, F. Bringaud,, and T. Baltz. 1998. Trypanosome glucose transporters. Mol. Biochem. Parasitol. 91: 195 205.
8. Barry, J. D. 1997. The relative significance of mechanisms of antigenic variation in African trypanosomes. Parasitol. Today 13: 212 217.
9. Barry, J. D.,, S. V. Graham,, M. Fotheringham,, K. Kobryn,, and B. Wymer. 1998. VSG gene control and infectivity strategy of metacyclic stage Trypanosoma brucei. Mol. Biochem. Parasitol. 91: 93 105.
10. Bernards, A.,, P. A. Michels,, C. R. Lincke,, and P. Borst. 1983. Growth of chromosome ends in multiplying trypanosomes. Nature 303: 592 597.
11. Bernards, A.,, L. H. Van der Ploeg,, A. C. Frasch,, P. Borst,, J. C. Boothroyd,, S. Coleman,, and G. A. Cross. 1981. Activation of trypanosome surface glycoprotein genes involves a duplication- transposition leading to an altered 3′end. Cell 27: 497 505.
12. Bitter, W.,, H. Gerrits,, R. Kieft,, and P. Borst. 1998. How Trypanosoma brucei may cope with the diversity of transferrins in its mammalian hosts. Nature 391: 499 502.
13. Blum, M. L.,, J. A. Down,, A. M. Gurnett,, M. Carrington,, M. J. Turner,, and D. C. Wiley. 1993. A structural motif in the variant surface glycoproteins of Trypanosoma brucei. Nature 362: 603 609.
14. Blundell, P. A.,, G. Rudenko,, and P. Borst. 1996. Targeting of exogenous DNA into Trypanosoma brucei requires a high degree of homology between donor and target DNA. Mol. Biochem. Parasitol. 76: 215 229.
15. Borst, P., 1983. Antigenic variation in trypanosomes, p. 621 659. In J. A. Shapiro (ed.), Mobile Genetic Elements. Academic Press, New York, N.Y.
16. Borst, P. 1986. Discontinuous transcription and antigenic variation in trypanosomes. Annu. Rev. Biochem. 55: 701 732.
17. Borst, P.,, W. Bitter,, P. A. Blundell,, I. Chaves,, M. Cross,, H. Gerrits,, F. Van Leeuwen,, R. McCulloch,, M. Taylor,, and G. Rudenko. 1998. Control of VSG gene expression sites in Trypanosoma brucei. Mol. Biochem. Parasitol. 91: 67 76.
18. Borst, P.,, W. Bitter,, P. Blundell,, M. Cross,, R. McCulloch,, G. Rudenko,, M. C. Taylor,, and F. Van Leeuwen,. 1997. The expression sites for variant surface glycoproteins of Trypanosoma brucei, p. 109 131. In G. Hide,, J. C. Mottram,, G. H. Coombs,, and P. H. Holmes (ed.), Trypanosomiasis and Leishmaniasis: Biology and Control. British Society for Parasitology and CAB International, Oxford, United Kingdom.
19. Borst, P.,, W. Bitter,, R. McCulloch,, F. Van Leeuwen,, and G. Rudenko. 1995. Antigenic variation in malaria. Cell 82: 1 4.
20. Borst, P.,, and A. H. Fairlamb. 1998. Surface receptors and transporters of Trypanosoma brucei. Annu. Rev. Microbiol. 52: 745 778.
21. Borst, P.,, and D. R. Greaves. 1987. Programmed gene rearrangements altering gene expression. Science 235: 658 667.
22. Borst, P.,, G. Rudenko,, P. A. Blundell,, F. Van Leeuwen,, M. A. Cross,, R. McCulloch,, H. Gerrits,, and I. M. F. Chaves. 1997. Mechanisms of antigenic variation in African trypanosomes. Behring Inst. Mitt. 99: 1 15.
23. Borst, P.,, G. Rudenko,, M. C. Taylor,, P. A. Blundell,, F. Van Leeuwen,, W. Bitter,, M. Cross,, and R. McCulloch. 1996. Antigenic variation in trypanosomes. Arch. Med. Res. 27: 379 388.
24. Bowman, S.,, D. Lawson,, D. Basham,, D. Brown,, T. Chillingworth,, C. M. Churcher,, A. Craig,, R. M. Davies,, K. Devlin,, T. Feltwell,, S. Gentles,, R. Gwilliam,, N. Hamlin,, D. Harris,, S. Holroyd,, T. Hornsby,, P. Horrocks,, B. Jagels,, S. Kyes,, J. McLean,, S. Moule,, K. Mungall,, L. Murphy,, and B. G. Barrell. 1999. The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum. Nature 400: 532 538.
25. Capbern, A.,, C. Giroud,, T. Baltz,, and P. Mattern. 1977. Trypanosoma equiperdum: étude des variations antigéniques au cours de la trypanosome expérimentale du lapin. Exp. Parasitol. 42: 6 13.
26. Chaves, I. 2000. Regulation of variant surface glycoprotein gene expression sites in Trypanosoma brucei. Ph.D. thesis. University of Oporto, Oporto, Portugal.
27. Chaves, I.,, J. Zomerdijk,, A. Dirks-Mulder,, R. W. Dirks,, A. K. Raap,, and P. Borst. 1998. Subnuclear localisation of the active variant surface glycoprotein gene expression site in Trypanosoma brucei. Proc. Natl. Acad. Sci. USA 95: 12328 12333.
28. Chaves, I.,, G. Rudenko,, A. Dirks-Mulder,, M. Cross,, and P. Borst. 1999. Control of variant surface glycoprotein gene expression sites in Trypanosoma brucei. EMBO J. 18: 4846 4855.
29. Chen, Q.,, V. Fernandez,, A. Sundström,, M. Schlichthere,, S. Datta,, P. Hagblom,, and M. Wahlgren. 1998. Developmental selection of var gene expression in Plasmodium falciparum. Nature 394: 392 395.
30. Coppens, I.,, F. R. Opperdoes,, P. J. Courtoy,, and P. Baudhuin. 1987. Receptor-mediated endocytosis in the bloodstream form of Trypanosoma brucei. J. Protozool. 34: 465 473.
31. Cornelissen, A. W.,, G. A. Bakkeren,, J. D. Barry,, P. A. Michels,, and P. Borst. 1985. Characteristics of trypanosome variant antigen genes active in the tsetse fly. Nucleic Acids Res. 13: 4661 4676.
32. Cross, G. A. M. 1975. Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of Trypanosoma brucei. Parasitology 71: 393 417.
33. Cross, G. A. M. 1996. Antigenic variation in trypanosomes: secrets surface slowly. Bioessays 18: 283 291.
34. Cross, M.,, M. C. Taylor,, and P. Borst. 1998. Frequent loss of the active site during VSG expression site switching in vitro in Trypanosoma brucei. Mol. Cell. Biol. 18: 198 205.
35. Cross, G. A. M.,, L. E. Wirtz,, and M. Navarro. 1998. Regulation of vsg expression site transcription and switching in Trypanosoma brucei. Mol. Biochem. Parasitol. 91: 77 91.
36. Crozatier, M.,, L. H. Van der Ploeg,, P. J. Johnson,, J. Gommers-Ampt,, and P. Borst. 1990. Structure of a telomeric expression site for variant specific surface antigens in Trypanosoma brucei. Mol. Biochem. Parasitol. 42: 1 12.
37. Deitsch, K. W.,, A. del Pinal,, and T. E. Wellems. 1999. Intracluster recombination and var transcription switches in the antigenic variation of Plasmodium falciparum. Mol. Biochem. Parasitol. 101: 107 116.
38. Deitsch, K. W.,, E. R. Moxon,, and T. E. Wellems. 1997. Shared themes of antigenic variation and virulence in bacterial, protozoal, and fungal infections. Microbiol. Mol. Biol. Rev. 61: 281 293.
39. Deitsch, K. W.,, and T. E. Wellems. 1996. Membrane modifications in erythrocytes parasitized by Plasmodium falciparum. Mol. Biochem. Parasitol. 76: 1 10.
40. De Lange, T.,, J. M. Kooter,, P. A. Michels,, and P. Borst. 1983. Telomere conversion in trypanosomes. Nucleic Acids Res. 11: 8149 8165.
41. Donelson, J. E. 1995. Mechanisms of antigenic variation in Borrelia hermsii and African trypanosomes. J. Biol. Chem. 270: 7783 7786.
42. Donelson, J. E.,, K. L. Hill,, and N. M. A. El-Sayed. 1998. Multiple mechanisms of immune evasion by African trypanosomes. Mol. Biochem. Parasitol. 91: 51 66.
43. Edman, J. C.,, T. W. Hatton,, M. Nam,, R. Turner,, Q. Mei,, C. W. Angus,, and J. A. Kovacs. 1996. A single expression site with a conserved leader sequence regulates variation of expression of the Pneumocystis carinii family of major surface glycoprotein genes. DNA Cell Biol. 15: 989 999.
44. El-Sayed, N. M.,, P. Hegde,, J. Quackenbush,, S. E. Melville,, and J. E. Donelson. 2000. The African trypanosome genome. Int. J. Parasitol. 30: 329 345.
45. Freitas-Junior, L. H.,, E. Bottius,, L. A. Pirrit,, K. Deitsch,, C. Scheidig,, F. Guinet,, U. Nehrbass,, T. Wellems,, and A. Scherf. 2000. Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum. Nature 407: 1018 1022.
46. Gardner, M. J.,, H. Tettelin,, D. J. Carucci,, L. M. Cummings,, L. Aravind,, E. V. Koonin,, S. Shallom,, T. Mason,, K. Yu,, C. Fujii,, J. Pederson,, K. Shen,, C. Aston,, Z. Lai,, D. C. Schwartz,, M. Pertea,, S. Salzberg,, L. Zhou,, G. G. Sutton,, R. Clayton,, O. White,, H. O. Smith,, C. M. Fraser,, and S. L. Hoffman. 1998. Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. Science 282: 1126 1132.
47. Gillin, F. D.,, P. Hagblom,, J. Harwood,, S. B. Aley,, D. S. Reiner,, J. M. McCaffery,, M. So,, and D. G. Guiney. 1990. Isolation and expression of the gene for a major surface protein of Giardia lamblia. Proc. Natl. Acad. Sci. USA 87: 4463 4467.
48. Gommers-Ampt, J. H.,, F. Van Leeuwen,, A. L. J. De Beer,, F. G. Vliegenthart,, M. Dizdaroglu,, J. A. Kowalak,, P. F. Crain,, and P. Borst. 1993. β-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan Trypanosoma brucei. Cell 75: 1129 1136.
49. Gould, G. W.,, and G. D. Holman. 1993. The glucose transporter family: structure, function and tissue-specific expression. Biochem. J. 295: 329 341.
50. Graham, S. V.,, and J. D. Barry. 1991. Expression site-associated genes transcribed independently of variant surface glycoprotein genes in Trypanosoma brucei. Mol. Biochem. Parasitol. 47: 31 42.
51. Graham, S. V.,, and J. D. Barry. 1995. Transcriptional regulation of metacyclic variant surface glycoprotein gene expression during the life cycle of Trypanosoma brucei. Mol. Cell. Biol. 15: 5945 5956.
52. Graham, S. V.,, S. Terry,, and J. D. Barry. 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.
53. Graham, S. V.,, B. Wymer,, and J. D. Barry. 1998. Activity of a trypanosome metacyclic variant surface glycoprotein gene promoter is dependent upon life cycle stage and chromosomal context. Mol. Cell. Biol. 18: 1137 1146.
54. Greaves, D. R.,, and P. Borst. 1987. Trypanosoma brucei variant- specific glycoprotein gene chromatin is sensitive to single- strand-specific endonuclease digestion. J. Mol. Biol. 197: 471 483.
55. Haber, J. E. 1999. DNA recombination: the replication connection. Trends Biochem. Sci. 24: 271 275.
56. Hernandez-Rivas, R.,, D. Mattei,, Y. Sterkers,, D. S. Peterson,, T. E. Wellems,, and A. Scherf. 1997. Expressed var genes are found in Plasmodium falciparum subtelomeric regions. Mol. Cell. Biol. 17: 604 611.
57. Huang, S. N.,, C. W. Angus,, R. E. Turner,, V. Sorial,, and J. A. Kovacs. 1999. Identification and characterization of novel variant major surface glycoprotein gene families in rat Pneumocystis carinii. J. Infect. Dis. 179: 192 2000.
58. Johnson, P. J.,, J. M. Kooter,, and P. Borst. 1987. Inactivation of transcription by UV irradiation of T. brucei provides evidence for a multicistronic transcription unit including a VSG gene. Cell 51: 273 281.
59. Keely, S. P.,, M.T. Cushion,, and J. R. Stringer. 1999. Determination of the maximum frequency of genetic rearrangements associated with Pneumocystis carinii surface antigen variation. J. Eukaryot. Microbiol. 46: 128S.
60. Kooter, J. M.,, H. J. van der Spek,, R. Wagter,, C. E. d’Oliveira,, F. van der Hoeven,, P. J. Johnson,, and P. Borst. 1987. The anatomy and transcription of a telomeric expression site for variant-specific surface antigens in T. brucei. Cell 51: 261 272.
61. Kooter, J. M.,, A. J. Winter,, C. de Oliveira,, R. Wagter,, and P. Borst. 1988. Boundaries of telomere conversion in Trypanosoma brucei. Gene 69: 1 11.
62. Liu, A. Y.,, P. A. Michels,, A. Bernards,, and P. Borst. 1985. Trypanosome variant surface glycoprotein genes expressed early in infection. J. Mol. Biol. 182: 383 396.
63. Liu, A. Y.,, L. H. T. Van der Ploeg,, F. A. Rijsewijk,, and P. Borst. 1983. 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. 167: 57 75.
64. Malkova, A.,, E. L. Ivanov,, and J. E. Haber. 1996. Doublestrand break repair in the absence of RAD51 in yeast: a possible role for break-induced DNA replication. Proc. Natl. Acad. Sci. USA 93: 7131 7136.
65. Matic, I.,, C. Rayssiguier,, and M. Radman. 1995. Interspecies gene exchange in bacteria: the role of SOS and mismatch repair systems in evolution of species. Cell 80: 507 515.
66. Matthews, K. R.,, P. G. Shiels,, S. V. Graham,, C. Cowan,, and J. D. Barry. 1990. Duplicative activation mechanisms of two trypanosome telomeric VSG genes with structurally simple 5′ flanks. Nucleic Acids Res. 18: 7219 7227.
67. McCulloch, R.,, and J. D. Barry. 1999. A role for RAD51 and homologous recombination in Trypanosoma brucei antigenic variation. Genes Dev. 13: 2875 2888.
68. McCulloch, R.,, G. Rudenko,, and P. Borst. 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.
69. Michels, P. A.,, A. Y. Liu,, A. Bernards,, P. Sloof,, M. M. Van der Bijl,, A. H. Schinkel,, H. H. Menke,, P. Borst,, G. H. Veeneman,, M. C. Tromp,, and J. H. Van Boom. 1983. Activation of the genes for variant surface glycoproteins 117 and 118 in Trypanosoma brucei. J. Mol. Biol. 166: 537 556.
70. Myler, P. J.,, R. F. Aline Jr.,, J. K. Scholler,, and K. D. Stuart. 1988. Changes in telomere length associated with antigenic variation in Trypanosoma brucei. Mol. Biochem. Parasitol. 29: 243 250.
71. Nagoshi, Y. L.,, C. M. Alarcon,, and J. E. Donelson. 1995. The putative promoter for a metacyclic VSG gene in African trypanosomes. Mol. Biochem. Parasitol. 72: 33 45.
72. Nakamura, Y.,, and M. Wada. 1998. Molecular pathobiology and antigenic variation of Pneumocystis carinii. Adv. Parasitol 41: 63 107.
73. Nash, T. E. 1997. Antigenic variation in Giardia lamblia and the host’s immune response. Philos. Trans. R. Soc. Lond. B 352: 1369 1375.
74. Nash, T. E.,, and M. R. Mowatt. 1992. Characterization of a Giardia lamblia variant-specific surface protein (VSP) gene from isolate GS/M and estimation of the VSP gene repertoire size. Mol. Biochem. Parasitol. 51: 219 228.
75. Nassif, N.,, J. Penney,, S. Pal,, W. R. Engels,, and G. B. Gloor. 1994. Efficient copying of nonhomologous sequences from ectopic sites via P-element-induced gap repair. Mol. Cell. Biol. 14: 1613 1625.
76. Navarro, M.,, G. A. M. Cross,, and E. Wirtz. 1999. Trypanosoma brucei variant surface glycoprotein regulation involves coupled activation/inactivation and chromatin remodeling of expression sites. EMBO J. 18: 2265 2272.
77. Newbold, C. I. 1999. Antigenic variation in Plasmodium falciparum: mechanisms and consequences. Curr. Opin. Microbiol. 2: 420 425.
78. Overath, P.,, Y.-D. Stierhof,, and M. Wiese. 1997. Endocytosis and secretion in trypanosomatid parasites—tumultuous traffic in a pocket. Trends Cell Biol. 7: 27 33.
79. Pays, E. 1989. Pseudogenes, chimaeric genes and the timing of antigen variation in African trypanosomes. Trends Genet. 5: 389 391.
80. Pays, E.,, M. Guyaux,, D. Aerts,, N. Van Meirvenne,, and M. Steinert. 1985. Telomeric reciprocal recombination as a possible mechanism for antigenic variation in trypanosomes. Nature 316: 562 564.
81. Pays, E.,, and D. P. Nolan. 1998. Expression and function of surface proteins in Trypanosoma brucei. Mol. Biochem. Parasitol. 91: 3 36.
82. Pays, E.,, P. Tebabi,, A. Pays,, H. Coquelet,, P. Revelard,, D. Salmon,, and M. Steinert. 1989. The genes and transcripts of an antigen gene expression site from T. brucei. Cell 57: 835 845.
83. Pays, E.,, L. Vanhamme,, and M. Berberof. 1994. Genetic controls for the expression of surface antigens in African trypanosomes. Annu. Rev. Microbiol. 48: 25 52.
84. Pedram, M.,, and J. E. Donelson. 1999. The anatomy and transcription of a monocistronic expression site for a meta cyclic variant surface glycoprotein gene in T. brucei. J. Biol. Chem. 274: 16876 16883.
85. Revelard, P.,, S. Lips,, and E. Pays. 1990. A gene from the VSG expression site of Trypanosoma brucei encodes a protein with both leucine-rich repeats and a putative zinc finger. Nucleic Acids Res. 18: 7299 7303.
86. Robinson, N. P.,, N. Burman,, S. E. Melville,, and J. D. Barry. 1999. Predominance of duplicative VSG gene conversion in antigenic variation in African trypanosomes. Mol. Cell. Biol. 19: 5839 5846.
87. Roth, C.,, F. Bringaud,, R. E. Layden,, T. Baltz,, and H. Eisen. 1989. Active late-appearing variable surface antigen genes in Trypanosoma equiperdum are constructed entirely from pseudogenes. Proc. Natl. Acad. Sci. USA 86: 9375 9379.
88. Rudenko, G. 1999. Genes involved in phenotypic and antigenic variation in African trypanosomes and malaria. Curr. Opin. Microbiol. 2: 651 656.
89. Rudenko, G.,, P. A. Blundell,, A. Dirks-Mulder,, R. Kieft,, and P. Borst. 1995. A ribosomal DNA promoter replacing the promoter of a telomeric variant surface glycoprotein gene expression site can be efficiently switched on and off in Trypanosoma brucei. Cell 83: 547 553.
90. Rudenko, G.,, I. Chaves,, A. Dirks-Mulder,, and P. Borst. 1998. Selection for activation of a new VSG gene expression site in Trypanosoma brucei in vitro can uncover events deleting the old expression site. Mol. Biochem. Parasitol. 95: 97 109.
91. Rudenko, G.,, M. Cross,, and P. Borst. 1998. Changing the end: antigenic variation at the telomeres of African trypanosomes. Trends Microbiol. 3: 113 117.
92. Rudenko, G.,, R. McCulloch,, A. Dirks-Mulder,, and P. Borst. 1996. Telomere exchange can be an important mechanism of variant surface glycoprotein gene switching in Trypanosoma brucei. Mol. Biochem. Parasitol. 80: 65 75.
93. Salmon, D.,, J. Hanocq-Quertier,, F. Paturiaux-Hanocq,, A. Pays,, P. Tebabi,, D. Nolan,, A. Michel,, and E. Pays. 1997. Characterization of the ligand-binding site of the transferrin receptor in Trypanosoma brucei demonstrates a structural relationship with the N-terminal domain of the variant surface glycoprotein. EMBO J. 16: 7272 7278.
94. Schaffzin, J. K.,, S. M. Sunkin,, and J. R. Stringer. 1999. A new family of Pneumocystis carinii genes related to those encoding the major surface glycoprotein. Curr. Genet. 35: 134 143.
95. Schaffzin, J. K.,, and J. R. Stringer. 2000. The major surface glycoprotein expression sites of two special forms of rat Pneumocystis carinii differ in structure. J. Infect. Dis. 181: 1729 1739.
96. Scherf, A.,, R. Hernandez-Rivas,, P. Buffet,, E. Bottius,, C. Benatar,, B. Pouvelle,, J. Gysin,, and M. Lanzer. 1998. Antigenic variation in malaria: in situ switching, relaxed and mutually exclusive transcription of var genes during intra-erythrocytic development in Plasmodium falciparum. EMBO J. 17: 5418 5426.
97. Scholler, J. K.,, P. J. Myler,, and K. D. Stuart. 1989. A novel telomeric gene conversion in Trypanosoma brucei. Mol. Biochem. Parasitol. 35: 11 19.
98. Shea, C.,, D. J. Glass,, S. Parangi,, and L. H. T. Van der Ploeg. 1986. VSG gene expression site switches in T. brucei. J. Biol. Chem. 261: 5056 5063.
99. Snounou, G.,, W. Jarra,, and P. R. Preiser. 2000. Malaria multigene families: the price of chronicity. Parasitol. Today 16: 28 30.
100. Sunkin, S. M.,, and J. R. Stringer. 1996. Translocation of surface antigen genes to a unique telomeric expression site in Pneumocystis carinii. Mol. Microbiol. 19: 283 295.
101. Sunkin, S. M.,, and J. R. Stringer. 1997. Residence at the expression site is necessary and sufficient for the transcription of surface antigen genes of Pneumocystis carinii. Mol. Microbiol. 25: 147 1.
102. Svärd, S.,, T. C. Meng,, M. L. Hetsko,, J. M. McCaffery,, and F. D. Gillin. 1998. Differentiation-associated surface antigen variation in the ancient eukaryote Giardia lamblia. Mol. Microbiol. 30: 979 989.
103. Thon, G.,, T. Baltz,, and H. Eisen. 1989. Antigenic diversity by the recombination of pseudogenes. Genes Dev. 3: 1247 1254.
104. Thon, G.,, T. Baltz,, C. Giroud,, and H. Eisen. 1990. Trypanosome variable surface glycoproteins: composite genes and order of expression. Genes Dev. 9: 1374 1383.
105. Timmers, H. T.,, T. De Lange,, J. M. Kooter,, and P. Borst. 1987. Coincident multiple activations of the same surface antigen gene in Trypanosoma brucei. J. Mol. Biol. 194: 81 90.
106. Turner, C. M. R.,, and J. D. Barry. 1989. High frequency of antigenic variation in Trypanosoma brucei rhodesiense infections. Parasitology 99: 67 75.
107. Turner, C. M. R.,, J. D. Barry,, I. Maudlin,, and K. Vickerman. 1988. An estimate of the size of the metacyclic variable antigen repertoire of Trypanosoma brucei rhodesiense. Parasitology 97: 269 276.
108. Upcroft, P.,, N. Chen,, and J. A. Upcroft. 1997. Telomeric organization of a variable and inducible toxin gene family in the ancient eukaryote Giardia duodenalis. Genome Res. 7: 37 46.
109. Van Asperen, J.,, U. Mayer,, O. Van Tellingen,, and J. H. Beijnen. 1997. The functional role of P-glycoprotein in the bloodbrain barrier. J. Pharm. Sci. 86: 881 884.
110. Van der Ploeg, L. H.,, D. C. Schwartz,, C. R. Cantor,, and P. Borst. 1984. Antigenic variation in Trypanosoma brucei analyzed by electrophoretic separation of chromosome-sized DNA molecules. Cell 37: 77 84.
111. Van der Ploeg, L. H.,, D. Valerio,, T. De Lange,, A. Bernards,, P. Borst,, and F. G. Grosveld. 1982. 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. 10: 5905 5923.
112. Vanhamme, L.,, and E. Pays. 1995. Control of gene expression in trypanosomes. Microbiol. Rev. 59: 223 240.
113. Vanhamme, L.,, P. Poelvoorde,, A. Pays,, P. Tebabi,, H. V. Xong,, and E. Pays. 2000. Differential RNA elongation controls the variant surface glycoprotein gene expression sites of Trypanosoma brucei. Mol. Microbiol. 36: 328 340.
114. Van Leeuwen, F.,, E. R. Wijsman,, R. Kieft,, G. A. van der Marel,, J. H. Van Boom,, and P. Borst. 1997. Localisation of the modified base J in telomeric VSG gene expression sites of Trypanosoma brucei. Genes Dev. 11: 3232 3241.
115. Wada, M.,, and Y. Nakamura. 1996. Antigenic variation by telomeric recombination of major-surface-glycoprotein genes of Pneumocystis carinii. J. Eukaryot. Microbiol. 43: 8S.
116. Wada, M.,, and Y. Nakamura. 1999. Type-II major surface glycoprotein family of Pneumocystis carinii under the control of novel expression elements. DNA Res. 6: 211 217.
117. Wada, M.,, S. M. Sunkin,, J. R. Stringer,, and Y. Nakamura. 1995. Antigenic variation by positional control of major surface glycoprotein gene expression in Pneumocystis carinii. J. Infect. Dis. 171: 1563 1568.
118. Wahlgren, M.,, V. Fernandez,, Q. Chen,, S. Svärd,, and P. Hagblom. 1999. Waves of malarial variations. Cell 96: 603 606.
119. Wakefield, A. E.,, J. R. Stringer,, E. Tamburrini,, and E. Dei- Cas. 1998. Genetics, metabolism and host specificity of Pnemocystis carinii. Med. Mycology 36: 183 193.
120. Waterkeyn, J. G.,, M. E. Wickham,, K. M. Davern,, B. M. Cooke,, R. L. Coppel,, J. C. Reeder,, J. G. Culvenor,, R. F. Waller,, and A. F. Cowman. 2000. Targeted mutagenesis of Plasmodium falciparum erythrocyte membrane protein 3 (PfEMP3) disrupts cytoadherence of malaria-infected red blood cells. EMBO J. 19: 2813 2823.
121. Weiden, M.,, Y. N. Osheim,, A. L. Beyer,, and L. H. T. Van der Ploeg. 1991. Chromosome structure DNA nucleotide sequence elements of a subset of the minichromosomes of the protozoan Trypanosoma brucei. Mol. Cell. Biol. 11: 3823 3834.
122. Xong, H. V.,, L. Vanhamme,, M. Chamekh,, C. E. Chimfwembe,, J. Van den Abbeele,, A. Pays,, N. Van Meirvenne,, R. Hamers,, P. De Baetselier,, and E. Pays. 1998. A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense. Cell 95: 839 846.
123. Yang, Y.,, and R. D. Adam. 1994. Allele-specific expression of a variant-specific surface protein (VSP) of Giardia lamblia. Nucleic Acids Res. 22: 2102 2108.
124. Zomerdijk, J. C.,, R. Kieft,, M. Duyndam,, P. G. Shiels,, and P. Borst. 1991. Antigenic variation in Trypanosoma brucei: a telomeric expression site for variant-specific surface glycoprotein genes with novel features. Nucleic Acids Res. 19: 1359 1368.

Tables

Generic image for table
Table 1

Antigenic variation of eukaryotic parasites: mechanisms used to control expression of surface antigen genes

Citation: Borst P. 2002. Antigenic Variation in Eukaryotic Parasites, p 953-971. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch40

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error