Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Dec;86(23):9375–9379. doi: 10.1073/pnas.86.23.9375

Active late-appearing variable surface antigen genes in Trypanosoma equiperdum are constructed entirely from pseudogenes.

C Roth 1, F Bringaud 1, R E Layden 1, T Baltz 1, H Eisen 1
PMCID: PMC298498  PMID: 2574459

Abstract

The expression of genes coding for variable surface glycoproteins (VSGs) in Trypanosoma equiperdum is linked to duplicative transpositions of silent, basic copy sequences into telomere-linked expression sites. Examination of three independently derived late-appearing trypanosome clones expressing VSG-78 revealed that the expressed gene in all cases is composed of sequences derived from three or four individual silent genes. The 182 base pairs at the 3' end of the coding sequence are derived from one silent gene, the 3' donor. The remaining 5' segment is a mosaic structure containing variable-length segments derived from two, or perhaps three, related silent genes. All of the silent genes that participate in the construction of the VSG-78 expression-linked copy (ELC) genes contain multiple stop codons and are unable to code for VSGs. Individual silent pseudogenes complement one another in the mosaic structure of the 5' portions of the ELC genes and create functional VSG genes. The joining of the 3' and 5' portions of the composite genes occurs in short regions of homology and suggests a mechanism by which the ordered expression of the VSG genes is generated.

Full text

PDF
9375

Images in this article

9376Image
on p.9376
9378Image
on p.9378

Selected References

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

  1. 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]
  2. Buck G. A., Jacquemot C., Baltz T., Eisen H. Re-expression of an inactivated variable surface glycoprotein gene in Trypanosoma equiperdum. Gene. 1984 Dec;32(3):329–336. doi: 10.1016/0378-1119(84)90008-8. [DOI] [PubMed] [Google Scholar]
  3. Buck G. A., Longacre S., Raibaud A., Hibner U., Giroud C., Baltz T., Baltz D., Eisen H. Stability of expression-linked surface antigen gene in Trypanosoma equiperdum. Nature. 1984 Feb 9;307(5951):563–566. doi: 10.1038/307563a0. [DOI] [PubMed] [Google Scholar]
  4. Capbern A., Giroud C., Baltz T., Mattern P. Trypanosoma equiperdum: etude des variations antigéniques au cours de la trypanosomose experimentale du lapin. Exp Parasitol. 1977 Jun;42(1):6–13. doi: 10.1016/0014-4894(77)90055-8. [DOI] [PubMed] [Google Scholar]
  5. Donelson J. E., Rice-Ficht A. C. Molecular biology of trypanosome antigenic variation. Microbiol Rev. 1985 Jun;49(2):107–125. doi: 10.1128/mr.49.2.107-125.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  7. Haas R., Meyer T. F. The repertoire of silent pilus genes in Neisseria gonorrhoeae: evidence for gene conversion. Cell. 1986 Jan 17;44(1):107–115. doi: 10.1016/0092-8674(86)90489-7. [DOI] [PubMed] [Google Scholar]
  8. Liu A. Y., Michels P. A., Bernards A., Borst P. Trypanosome variant surface glycoprotein genes expressed early in infection. J Mol Biol. 1985 Apr 5;182(3):383–396. doi: 10.1016/0022-2836(85)90198-6. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Longacre S., Eisen H. Expression of whole and hybrid genes in Trypanosoma equiperdum antigenic variation. EMBO J. 1986 May;5(5):1057–1063. doi: 10.1002/j.1460-2075.1986.tb04322.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Longacre S., Hibner U., Raibaud A., Eisen H., Baltz T., Giroud C., Baltz D. DNA rearrangements and antigenic variation in Trypanosoma equiperdum: multiple expression-linked sites in independent isolates of trypanosomes expressing the same antigen. Mol Cell Biol. 1983 Mar;3(3):399–409. doi: 10.1128/mcb.3.3.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Merritt S. C., Tschudi C., Konigsberg W. H., Richards F. F. Reverse transcription of trypanosome variable antigen mRNAs initiated by a specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1536–1540. doi: 10.1073/pnas.80.6.1536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Messing J., Vieira J. A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments. Gene. 1982 Oct;19(3):269–276. doi: 10.1016/0378-1119(82)90016-6. [DOI] [PubMed] [Google Scholar]
  14. Myers R. M., Larin Z., Maniatis T. Detection of single base substitutions by ribonuclease cleavage at mismatches in RNA:DNA duplexes. Science. 1985 Dec 13;230(4731):1242–1246. doi: 10.1126/science.4071043. [DOI] [PubMed] [Google Scholar]
  15. Myler P. J., Allen A. L., Agabian N., Stuart K. Antigenic variation in clones of Trypanosoma brucei grown in immune-deficient mice. Infect Immun. 1985 Mar;47(3):684–690. doi: 10.1128/iai.47.3.684-690.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pays E., Houard S., Pays A., Van Assel S., Dupont F., Aerts D., Huet-Duvillier G., Gomés V., Richet C., Degand P. Trypanosoma brucei: the extent of conversion in antigen genes may be related to the DNA coding specificity. Cell. 1985 Oct;42(3):821–829. doi: 10.1016/0092-8674(85)90278-8. [DOI] [PubMed] [Google Scholar]
  17. Pays E., Van Assel S., Laurent M., Darville M., Vervoort T., Van Meirvenne N., Steinert M. Gene conversion as a mechanism for antigenic variation in trypanosomes. Cell. 1983 Sep;34(2):371–381. doi: 10.1016/0092-8674(83)90371-9. [DOI] [PubMed] [Google Scholar]
  18. Pays E., Van Meirvenne N., Le Ray D., Steinert M. Gene duplication and transposition linked to antigenic variation in Trypanosoma brucei. Proc Natl Acad Sci U S A. 1981 May;78(5):2673–2677. doi: 10.1073/pnas.78.5.2673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reynaud C. A., Anquez V., Grimal H., Weill J. C. A hyperconversion mechanism generates the chicken light chain preimmune repertoire. Cell. 1987 Feb 13;48(3):379–388. doi: 10.1016/0092-8674(87)90189-9. [DOI] [PubMed] [Google Scholar]
  20. Roth C. W., Longacre S., Raibaud A., Baltz T., Eisen H. The use of incomplete genes for the construction of a Trypanosoma equiperdum variant surface glycoprotein gene. EMBO J. 1986 May;5(5):1065–1070. doi: 10.1002/j.1460-2075.1986.tb04323.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  22. Swanson J., Bergström S., Robbins K., Barrera O., Corwin D., Koomey J. M. Gene conversion involving the pilin structural gene correlates with pilus+ in equilibrium with pilus- changes in Neisseria gonorrhoeae. Cell. 1986 Oct 24;47(2):267–276. doi: 10.1016/0092-8674(86)90449-6. [DOI] [PubMed] [Google Scholar]
  23. Thon G., Baltz T., Eisen H. Antigenic diversity by the recombination of pseudogenes. Genes Dev. 1989 Aug;3(8):1247–1254. doi: 10.1101/gad.3.8.1247. [DOI] [PubMed] [Google Scholar]
  24. Williams R. O., Young J. R., Majiwa P. A. Genomic rearrangements correlated with antigenic variation in Trypanosoma brucei. Nature. 1979 Dec 20;282(5741):847–849. doi: 10.1038/282847a0. [DOI] [PubMed] [Google Scholar]
  25. Young J. R., Miller E. N., Williams R. O., Turner M. J. Are there two classes of VSG gene in Trypanosoma brucei? Nature. 1983 Nov 10;306(5939):196–198. doi: 10.1038/306196a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES