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Molecular and Cellular Biology, September 1999, p. 5839-5846, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Predominance of Duplicative VSG Gene
Conversion in Antigenic Variation in African Trypanosomes
Nicholas P.
Robinson,1
Nils
Burman,1,
Sara E.
Melville,2 and
J.
David
Barry1,*
Wellcome Centre for Molecular Parasitology,
University of Glasgow, Anderson College, Glasgow G11 6NU,
Scotland,1 and Department of Pathology,
Cambridge University, Cambridge CB2 1QP, England2
Received 17 February 1999/Returned for modification 9 April
1999/Accepted 19 June 1999
A number of mechanisms have been described by which African
trypanosomes undergo the genetic switches that differentially activate
their variant surface glycoprotein genes (VSGs) and bring about antigenic variation. These mechanisms have been observed mainly
in trypanosome lines adapted, by rapid syringe passaging, to laboratory
conditions. Such "monomorphic" lines, which routinely yield only
the proliferative bloodstream form and do not develop through their
life cycle, have VSG switch rates up to 4 or 5 orders of magnitude
lower than those of nonadapted lines. We have proposed that nonadapted,
or pleomorphic, trypanosomes normally have an active VSG
switch mechanism, involving gene duplication, that is depressed, or
from which a component is absent, in monomorphic lines. We have
characterized 88 trypanosome clones from the first two relapse peaks of
a single rabbit infection with pleomorphic trypanosomes and shown that
they represent 11 different variable antigen types (VATs). The pattern
of appearance in the first relapse peak was generally reproducible in
three more rabbit infections. Nine of these VATs had activated
VSGs by gene duplication, the tenth possibly also had done
so, and only one had activated a VSG by the transcriptional
switch mechanism that predominates in monomorphic lines. At least 10 of
the donor genes have telomeric silent copies, and many reside on
minichromosomes. It appears that trypanosome antigenic variation is
dominated by one, relatively highly active, mechanism rather than by
the plethora of pathways described before.
*
Corresponding author. Mailing address: Wellcome Centre
for Molecular Parasitology, University of Glasgow, The Anderson
College, 56 Dumbarton Rd., Glasgow G11 5JS, Scotland, United Kingdom.
Phone: 44 (0)141 330 4875. Fax: 44 (0)141 330 5422. E-mail:
j.d.barry{at}bio.gla.ac.uk.

Present address: Department of Laboratory Medicine, County
Hospital, Boden,
Sweden.
Molecular and Cellular Biology, September 1999, p. 5839-5846, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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