Abstract
In Trypanosoma brucei telomeric copies of intrachromosomal variant surface glycoprotein (VSG) genes are produced through a gene conversion mechanism and are expressed if the telomere is or becomes transcriptionally activated. We have analyzed a sequence that occurs 1 to 1.5 kb 5' to several intrachromosomal VSG genes. This flanking sequence has three distinct sections: a 5' section containing 5 to 116 TAA or TAA-like tandem repeats; a moderately conserved sequence with an alternating GT characteristic; and a highly conserved 3' sequence that is largely alternating TA. Restriction mapping data and the location of this sequence suggest that it occurs at or near the 5' gene conversion boundary. This sequence, however, is not 5' to all VSG genes. These data suggest that this flanking sequence alone is not sufficient for VSG gene expression but that it may function in gene conversion for many, but not all, VSG genes.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allison J., Rothwell V., Newport G., Agabian N., Stuart K. The IsTat 1.3 VSG multigene family in Trypanosoma brucei: retention of the expression linked copy through multiple antigenic switches. Nucleic Acids Res. 1984 Dec 11;12(23):9051–9066. doi: 10.1093/nar/12.23.9051. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
- Boothroyd J. C., Cross G. A. Transcripts coding for variant surface glycoproteins of Trypanosoma brucei have a short, identical exon at their 5' end. Gene. 1982 Dec;20(2):281–289. doi: 10.1016/0378-1119(82)90046-4. [DOI] [PubMed] [Google Scholar]
- Borst P., Cross G. A. Molecular basis for trypanosome antigenic variation. Cell. 1982 Jun;29(2):291–303. doi: 10.1016/0092-8674(82)90146-5. [DOI] [PubMed] [Google Scholar]
- 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]
- De Lange T., Borst P. Genomic environment of the expression-linked extra copies of genes for surface antigens of Trypanosoma brucei resembles the end of a chromosome. Nature. 1982 Sep 30;299(5882):451–453. doi: 10.1038/299451a0. [DOI] [PubMed] [Google Scholar]
- Donelson J. E., Murphy W. J., Brentano S. T., Rice-Ficht A. C., Cain G. D. Comparison of the expression-linked extra copy (ELC) and basic copy (BC) genes of a trypanosome surface antigen. J Cell Biochem. 1983;23(1-4):1–12. doi: 10.1002/jcb.240230102. [DOI] [PubMed] [Google Scholar]
- Hoeijmakers J. H., Frasch A. C., Bernards A., Borst P., Cross G. A. Novel expression-linked copies of the genes for variant surface antigens in trypanosomes. Nature. 1980 Mar 6;284(5751):78–80. doi: 10.1038/284078a0. [DOI] [PubMed] [Google Scholar]
- Horowitz H., Haber J. E. Subtelomeric regions of yeast chromosomes contain a 36 base-pair tandemly repeated sequence. Nucleic Acids Res. 1984 Sep 25;12(18):7105–7121. doi: 10.1093/nar/12.18.7105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karn J., Brenner S., Barnett L., Cesareni G. Novel bacteriophage lambda cloning vector. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5172–5176. doi: 10.1073/pnas.77.9.5172. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Michiels F., Matthyssens G., Kronenberger P., Pays E., Dero B., Van Assel S., Darville M., Carvador A., Steinert M., Hamers R. Gene activation and re-expression of a Trypanosoma brucei variant surface glycoprotein. EMBO J. 1983;2(7):1185–1192. doi: 10.1002/j.1460-2075.1983.tb01565.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Milhausen M., Nelson R. G., Parsons M., Newport G., Stuart K., Agabian N. Molecular characterization of initial variants from the IsTat I serodeme of Trypanosoma brucei. Mol Biochem Parasitol. 1983 Nov;9(3):241–254. doi: 10.1016/0166-6851(83)90100-7. [DOI] [PubMed] [Google Scholar]
- Myler P. J., Allison J., Agabian N., Stuart K. Antigenic variation in African trypanosomes by gene replacement or activation of alternate telomeres. Cell. 1984 Nov;39(1):203–211. doi: 10.1016/0092-8674(84)90206-x. [DOI] [PubMed] [Google Scholar]
- Myler P., Nelson R. G., Agabian N., Stuart K. Two mechanisms of expression of a predominant variant antigen gene of Trypanosoma brucei. Nature. 1984 May 17;309(5965):282–284. doi: 10.1038/309282a0. [DOI] [PubMed] [Google Scholar]
- Nordheim A., Lafer E. M., Peck L. J., Wang J. C., Stollar B. D., Rich A. Negatively supercoiled plasmids contain left-handed Z-DNA segments as detected by specific antibody binding. Cell. 1982 Dec;31(2 Pt 1):309–318. doi: 10.1016/0092-8674(82)90124-6. [DOI] [PubMed] [Google Scholar]
- Parsons M., Nelson R. G., Newport G., Milhausen M., Stuart K., Agabian N. Genomic organization of Trypanosoma brucei variant antigen gene families in sequential parasitemias. Mol Biochem Parasitol. 1983 Nov;9(3):255–269. doi: 10.1016/0166-6851(83)90101-9. [DOI] [PubMed] [Google Scholar]
- 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]
- Pays E., Van Assel S., Laurent M., Dero B., Michiels F., Kronenberger P., Matthyssens G., Van Meirvenne N., Le Ray D., Steinert M. At least two transposed sequences are associated in the expression site of a surface antigen gene in different trypanosome clones. Cell. 1983 Sep;34(2):359–369. doi: 10.1016/0092-8674(83)90370-7. [DOI] [PubMed] [Google Scholar]
- 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]
- Rothwell V., Aline R., Jr, Parsons M., Agabian N., Stuart K. Expression of a minichromosomal variant surface glycoprotein gene in Trypanosoma brucei. Nature. 1985 Feb 14;313(6003):595–597. doi: 10.1038/313595a0. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith G. P. Evolution of repeated DNA sequences by unequal crossover. Science. 1976 Feb 13;191(4227):528–535. doi: 10.1126/science.1251186. [DOI] [PubMed] [Google Scholar]
- Strathern J. N., Klar A. J., Hicks J. B., Abraham J. A., Ivy J. M., Nasmyth K. A., McGill C. Homothallic switching of yeast mating type cassettes is initiated by a double-stranded cut in the MAT locus. Cell. 1982 Nov;31(1):183–192. doi: 10.1016/0092-8674(82)90418-4. [DOI] [PubMed] [Google Scholar]
- Stuart K., Gobright E., Jenni L., Milhausen M., Thomashow L., Agabian N. The IsTaR 1 serodeme of Trypanosoma brucei: development of a new serodeme. J Parasitol. 1984 Oct;70(5):747–754. [PubMed] [Google Scholar]
- Van der Ploeg L. H., Cornelissen A. W., Michels P. A., Borst P. Chromosome rearrangements in Trypanosoma brucei. Cell. 1984 Nov;39(1):213–221. doi: 10.1016/0092-8674(84)90207-1. [DOI] [PubMed] [Google Scholar]
- Van der Ploeg L. H., Schwartz D. C., Cantor C. R., Borst P. Antigenic variation in Trypanosoma brucei analyzed by electrophoretic separation of chromosome-sized DNA molecules. Cell. 1984 May;37(1):77–84. doi: 10.1016/0092-8674(84)90302-7. [DOI] [PubMed] [Google Scholar]
- 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]
- Wang A. H., Quigley G. J., Kolpak F. J., Crawford J. L., van Boom J. H., van der Marel G., Rich A. Molecular structure of a left-handed double helical DNA fragment at atomic resolution. Nature. 1979 Dec 13;282(5740):680–686. doi: 10.1038/282680a0. [DOI] [PubMed] [Google Scholar]
- Williams R. O., Young J. R., Majiwa P. A. Genomic environment of T. brucei VSG genes: presence of a minichromosome. Nature. 1982 Sep 30;299(5882):417–421. doi: 10.1038/299417a0. [DOI] [PubMed] [Google Scholar]
- Young J. R., Donelson J. E., Majiwa P. A., Shapiro S. Z., Williams R. O. analysis of genomic rearrangements associated with two variable antigen genes of Trypanosoma brucei. Nucleic Acids Res. 1982 Feb 11;10(3):803–819. doi: 10.1093/nar/10.3.803. [DOI] [PMC free article] [PubMed] [Google Scholar]