DNA rearrangements and antigenic variation in Trypanosoma equiperdum: expression-independent DNA rearrangements in the basic copy of a variant surface glycoprotein gene

1983 ◽  
Vol 3 (3) ◽  
pp. 410-414
Author(s):  
S Longacre ◽  
A Raibaud ◽  
U Hibner ◽  
G Buck ◽  
H Eisen ◽  
...  
Keyword(s):  
Gene Duplication ◽  
Antigenic Variation ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Dna Rearrangements ◽  
Present Evidence ◽  
Glycoprotein Gene ◽  
Copy Gene ◽  
Genomic Environment ◽  
Trypanosoma Equiperdum

Antigenic variation in Trypanosoma equiperdum is associated with the sequential expression of variant surface glycoprotein (VSG) genes in a process which involves gene duplication and transposition events. In this paper we present evidence that the genomic environment of the VSG-1 basic copy gene, the template for duplicated, expression-linked VSG-1 genes, differs in every trypanosome clone examined. This variation is thus independent of the expression of the VSG-1 gene, and it also appears to be restricted to the 3' genomic environment. It is also demonstrated that the DNA located 3' to the VSG-1 basic copy gene is moderately sensitive to digestion when the nuclei of either expressor or non-expressor trypanosomes are treated with DNase I.

scholarly journals DNA rearrangements and antigenic variation in Trypanosoma equiperdum: expression-independent DNA rearrangements in the basic copy of a variant surface glycoprotein gene.

1983 ◽  
Vol 3 (3) ◽  
pp. 410-414 ◽  
Author(s):  
S Longacre ◽  
A Raibaud ◽  
U Hibner ◽  
G Buck ◽  
H Eisen ◽  
...  
Keyword(s):  
Gene Duplication ◽  
Antigenic Variation ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Dna Rearrangements ◽  
Present Evidence ◽  
Glycoprotein Gene ◽  
Copy Gene ◽  
Genomic Environment ◽  
Trypanosoma Equiperdum

Antigenic variation in Trypanosoma equiperdum is associated with the sequential expression of variant surface glycoprotein (VSG) genes in a process which involves gene duplication and transposition events. In this paper we present evidence that the genomic environment of the VSG-1 basic copy gene, the template for duplicated, expression-linked VSG-1 genes, differs in every trypanosome clone examined. This variation is thus independent of the expression of the VSG-1 gene, and it also appears to be restricted to the 3' genomic environment. It is also demonstrated that the DNA located 3' to the VSG-1 basic copy gene is moderately sensitive to digestion when the nuclei of either expressor or non-expressor trypanosomes are treated with DNase I.

DNA rearrangements and antigenic variation in Trypanosoma equiperdum: multiple expression-linked sites in independent isolates of trypanosomes expressing the same antigen

1983 ◽  
Vol 3 (3) ◽  
pp. 399-409
Author(s):  
S Longacre ◽  
U Hibner ◽  
A Raibaud ◽  
H Eisen ◽  
T Baltz ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Mechanism ◽  
Antigenic Variation ◽  
Cdna Probe ◽  
Surface Glycoprotein ◽  
Dna Rearrangements ◽  
African Trypanosomes ◽  
Trypanosoma Equiperdum ◽  
Variant Surface Glycoproteins ◽  
Multiple Expression

African trypanosomes resist the immune response of their mammalian hosts by varying the surface glycoprotein which constitutes their antigenic identity. The molecular mechanism of this antigenic variation involves the successive activation of a series of genes which code for different variant surface glycoproteins (VSGs). We have studied the expression of two VSG genes (those of VSG-1 and VSG-28) in Trypanosoma equiperdum, and we report the following findings. (i) The expression of both VSG genes is associated with the duplication and transposition of corresponding basic copy genes. (ii) The duplicated transposed copy appears to be the expressed copy. (iii) Although there are multiple genes which cross-hybridize with the VSG-1 cDNA probe, only one of these appears to be used as a template for the expression-linked copy in four independent BoTat-1 clones. (iv) Analysis of the genomic environments of the expressed VSG-1 genes from each of four independently derived BoTat-1 trypanosome clones revealed that there are at least three different sites into which the expression-linked copy can be inserted.

Identification of potential protein partners that bind to the variant surface glycoprotein in Trypanosoma equiperdum

Parasitology ◽  
2017 ◽  
Vol 144 (7) ◽  
pp. 923-936 ◽  
Author(s):  
LIOMARY M. CARRASQUEL ◽  
JOSÉ L. ESCALONA ◽  
ALVARO ACOSTA-SERRANO ◽  
YURONG GUO ◽  
JOSÉ BUBIS
Keyword(s):  
Antigenic Variation ◽  
Orthologous Gene ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Western Blots ◽  
Binding Partners ◽  
Protein Partners ◽  
Expression Site ◽  
Tryparedoxin Peroxidase ◽  
Trypanosoma Equiperdum

SUMMARYTrypanosoma equiperdum possesses a dense coat of a variant surface glycoprotein (VSG) that is used to evade the host immune response by a process known as antigenic variation. Soluble and membrane forms of the predominant VSG from the Venezuelan T. equiperdum TeAp-N/D1 strain (sVSG and mVSG, respectively) were purified to homogeneity; and antibodies against sVSG and mVSG were raised, isolated, and employed to produce anti-idiotypic antibodies that structurally mimic the VSG surface. Prospective VSG-binding partners were initially detected by far-Western blots, and then by immunoblots using the generated anti-idiotypic antibodies. Polypeptides of ~80 and 55 kDa were isolated when anti-idiotypic antibodies–Sepharose affinity matrixes were used as baits. Mass spectrometry sequencing yielded hits with various proteins from Trypanosoma brucei such as heat-shock protein 70, tryparedoxin peroxidase, VSG variants, expression site associated gene product 6, and two hypothetical proteins. In addition, a possible interaction with a protein homologous to the glutamic acid/alanine-rich protein from Trypanosoma congolense was also found. These results indicate that the corresponding orthologous gene products are candidates for VSG-interacting proteins in T. equiperdum.

scholarly journals DNA rearrangements and antigenic variation in Trypanosoma equiperdum: multiple expression-linked sites in independent isolates of trypanosomes expressing the same antigen.

1983 ◽  
Vol 3 (3) ◽  
pp. 399-409 ◽  
Author(s):  
S Longacre ◽  
U Hibner ◽  
A Raibaud ◽  
H Eisen ◽  
T Baltz ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Mechanism ◽  
Antigenic Variation ◽  
Cdna Probe ◽  
Surface Glycoprotein ◽  
Dna Rearrangements ◽  
African Trypanosomes ◽  
Trypanosoma Equiperdum ◽  
Variant Surface Glycoproteins ◽  
Multiple Expression

African trypanosomes resist the immune response of their mammalian hosts by varying the surface glycoprotein which constitutes their antigenic identity. The molecular mechanism of this antigenic variation involves the successive activation of a series of genes which code for different variant surface glycoproteins (VSGs). We have studied the expression of two VSG genes (those of VSG-1 and VSG-28) in Trypanosoma equiperdum, and we report the following findings. (i) The expression of both VSG genes is associated with the duplication and transposition of corresponding basic copy genes. (ii) The duplicated transposed copy appears to be the expressed copy. (iii) Although there are multiple genes which cross-hybridize with the VSG-1 cDNA probe, only one of these appears to be used as a template for the expression-linked copy in four independent BoTat-1 clones. (iv) Analysis of the genomic environments of the expressed VSG-1 genes from each of four independently derived BoTat-1 trypanosome clones revealed that there are at least three different sites into which the expression-linked copy can be inserted.

scholarly journals Targeting the Variable Surface of African Trypanosomes with Variant Surface Glycoprotein-Specific, Serum-Stable RNA Aptamers

2003 ◽  
Vol 2 (1) ◽  
pp. 84-94 ◽  
Author(s):  
Mihaela Lorger ◽  
Markus Engstler ◽  
Matthias Homann ◽  
H. Ulrich Göringer
Keyword(s):  
Antigenic Variation ◽  
Sleeping Sickness ◽  
Rna Aptamers ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Parasite Protein ◽  
African Trypanosomes ◽  
Variable Surface ◽  
New Strategy

ABSTRACT African trypanosomes cause sleeping sickness in humans and Nagana in cattle. The parasites multiply in the blood and escape the immune response of the infected host by antigenic variation. Antigenic variation is characterized by a periodic change of the parasite protein surface, which consists of a variant glycoprotein known as variant surface glycoprotein (VSG). Using a SELEX (systematic evolution of ligands by exponential enrichment) approach, we report the selection of small, serum-stable RNAs, so-called aptamers, that bind to VSGs with subnanomolar affinity. The RNAs are able to recognize different VSG variants and bind to the surface of live trypanosomes. Aptamers tethered to an antigenic side group are capable of directing antibodies to the surface of the parasite in vitro. In this manner, the RNAs might provide a new strategy for a therapeutic intervention to fight sleeping sickness.

A strand bias occurs in point mutations associated with variant surface glycoprotein gene conversion in Trypanosoma rhodesiense

1994 ◽  
Vol 14 (6) ◽  
pp. 3971-3980
Author(s):  
Y Lu ◽  
C M Alarcon ◽  
T Hall ◽  
L V Reddy ◽  
J E Donelson
Keyword(s):  
Point Mutations ◽  
Cross Reactivity ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Strand Bias ◽  
Glycoprotein Gene ◽  
Coding Regions ◽  
Crossover Site ◽  
Sense Strand ◽  
Duplication Events

We previously described a bloodstream Trypansoma rhodesiense clone, MVAT5-Rx2, whose isolation was based on its cross-reactivity with a monoclonal antibody (MAb) directed against a metacyclic variant surface glycoprotein (VSG). When the duplicated, expressed VSG gene in MVAT5-Rx2 was compared with its donor (basic copy) gene, 11 nucleotide differences were found in the respective 1.5-kb coding regions (Y. Lu, T. Hall, L. S. Gay, and J. E. Donelson, Cell 72:397-406, 1993). Here we describe a characterization of two additional bloodstream trypanosome clones, MVAT5-Rx1 and MVAT5-Rx3, whose VSGs are expressed from duplicated copies of the same donor VSG gene. The three trypanosome clones each react with the MVAT5-specific MAb, but they have different cross-reactivities with a panel of other MAbs, suggesting that their surface epitopes are similar but nonidentical. Each of the three gene duplication events occurs at a different 5' crossover site within a 76-bp repeat and is associated with a different set of point mutations. The 35, 11, and 28 point mutations in the duplicated VSG coding regions of Rx1, Rx2, and Rx3, respectively, exhibit a strand bias. In the sense strand, of the 74 total mutations generated in the three duplications, 54% are A-to-G or G-to-A (A:G) transitions and 7% are C:T transitions, while 26% are C:A transversions and 13% are C:G transversions. No T:G or T:A transversions occurred. Possible models for the generation of these point mutations are discussed.

Expression of a retroposon-like sequence upstream of the putative Trypanosoma brucei variant surface glycoprotein gene expression site promoter

1993 ◽  
Vol 13 (11) ◽  
pp. 7036-7044
Author(s):  
M J Lodes ◽  
B L Smiley ◽  
A W Stadnyk ◽  
J L Bennett ◽  
P J Myler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Trypanosoma Brucei ◽  
Copy Number ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Putative Promoter ◽  
Glycoprotein Gene ◽  
Active Expression ◽  
Expression Site ◽  
Total Copy Number

We have cloned the region spanning the putative promoter from two variant surface glycoprotein gene expression sites that are at each end of chromosome M4 of Trypanosoma brucei IsTat 7. Both expression sites contain a retroposon-like sequence (ESR) pseudogene whose 3' end is approximately 30 bp upstream of the putative expression site promoter. The ESRs from both expression sites share considerable sequence homology and are related to LINE-like elements, especially the T. brucei ingi retroposon. Other ESRs are located on large, but not intermediate or mini-, chromosomes in the IsTaR 1 serodeme, and the total copy number is 10 to 20, similar to that estimated for variant surface glycoprotein expression sites. No DNA rearrangements in the vicinity of the ESR and putative expression site promoter were detected following antigenic switches in the IsTaR 1 serodeme. ESR transcripts are present in bloodstream, but not procyclic, forms. Variation in transcript size and sequence between bloodstream variant antigenic types implies that only the ESR from the active expression site is transcribed. This pattern of expression reflects that of sequences downstream of the putative expression site promoter, suggesting that the region of coordinately controlled expression extends upstream of this promoter.

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