The serum resistance-associated (SRA) gene of Trypanosoma brucei rhodesiense encodes a variant surface glycoprotein-like protein

SUMMARYTrypanosoma brucei is the causative agent of African sleeping sickness in humans and one of several pathogens that cause the related veterinary disease Nagana. A complex co-evolution has occurred between these parasites and primates that led to the emergence of trypanosome-specific defences and counter-measures. The first line of defence in humans and several other catarrhine primates is the trypanolytic protein apolipoprotein-L1 (APOL1) found within two serum protein complexes, trypanosome lytic factor 1 and 2 (TLF-1 and TLF-2). Two sub-species of T. brucei have evolved specific mechanisms to overcome this innate resistance, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. In T. b. rhodesiense, the presence of the serum resistance associated (SRA) gene, a truncated variable surface glycoprotein (VSG), is sufficient to confer resistance to lysis. The resistance mechanism of T. b. gambiense is more complex, involving multiple components: reduction in binding affinity of a receptor for TLF, increased cysteine protease activity and the presence of the truncated VSG, T. b. gambiense-specific glycoprotein (TgsGP). In a striking example of co-evolution, evidence is emerging that primates are responding to challenge by T. b. gambiense and T. b. rhodesiense, with several populations of humans and primates displaying resistance to infection by these two sub-species.

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Conservation of the genomic location of the human serum resistance associated gene in Trypanosoma brucei rhodesiense

Molecular and Biochemical Parasitology ◽

10.1016/s0166-6851(03)00168-3 ◽

2003 ◽

Vol 130 (2) ◽

pp. 159-162 ◽

Cited By ~ 14

Author(s):

Wendy Gibson ◽

Vanessa Ferris

Keyword(s):

Human Serum ◽

Trypanosoma Brucei ◽

Serum Resistance ◽

Trypanosoma Brucei Rhodesiense ◽

Genomic Location

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Frequent independent duplicative transpositions activate a single VSG gene

Molecular and Cellular Biology ◽

10.1128/mcb.7.1.357-364.1987 ◽

1987 ◽

Vol 7 (1) ◽

pp. 357-364

Author(s):

M G Lee ◽

L H Van der Ploeg

Keyword(s):

Gene Conversion ◽

Trypanosoma Brucei ◽

Surface Antigen ◽

Strong Evidence ◽

Base Pair ◽

Surface Glycoprotein ◽

Variant Surface Glycoprotein ◽

Gene Variants ◽

Repeat Array ◽

Expression Site

The expression of several surface antigen genes in Trypanosoma brucei is mediated by the duplicative transposition of a basic-copy variant surface glycoprotein (VSG) gene into an expression site. We determined that the appearance of variant 118, in a parasitemia, resulted from at least four independent duplicative transpositions of the same VSG 118 gene. Variants 117 and 118 both appeared at specific periods but resulted from multiple independent activations. Antigenic variants thus occur in an ordered manner. We show that in the duplicative transpositions of VSG genes, the ends of the transposed segments were homologous between the basic copy and the expression site. Sequences other than the previously reported 70-base-pair (bp) repeats could be involved. In one variant, 118 clone 1, the homology was between a sequence previously transposed into the expression site and a sequence located 6 kilobases upstream of the VSG 118 gene. In variant 118b the homology was presumably in 70-bp repeat arrays, while in a third 118 variant yet another sequence was involved. The possibility that the 70-bp repeats are important in the initial steps of the recombinational events was illustrated by a rearrangement involving a 70-bp repeat array. The data provide strong evidence for the notion that gene conversion mediates the duplicative transposition of VSG genes. We discuss a model that explains how the process of duplicative transposition can occur at random and still produce an ordered appearance of variants.

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Transient activity assays of the Trypanosoma brucei variant surface glycoprotein gene promoter: control of gene expression at the posttranscriptional level

Molecular and Cellular Biology ◽

10.1128/mcb.11.1.338-343.1991 ◽

1991 ◽

Vol 11 (1) ◽

pp. 338-343

Author(s):

D Jefferies ◽

P Tebabi ◽

E Pays

Keyword(s):

Trypanosoma Brucei ◽

Gene Promoter ◽

Surface Glycoprotein ◽

Variant Surface Glycoprotein ◽

Gene Promoters ◽

Control Of Gene Expression ◽

Transient Activity ◽

Expression Site ◽

Cat Gene ◽

Cat Expression

The putative promoter of the variant surface glycoprotein (VSG) gene of Trypanosoma brucei was cloned into a plasmid containing the chloramphenicol acetyltransferase (CAT) gene. After electroporation into trypanosomes, this construct directed the expression of the CAT reporter gene. The essential region for promoter activity was found to reside within 88 bp upstream of the putative transcription start site. Transcription of the CAT construct occurred at approximately the same level in both bloodstream and procyclic forms and was resistant to alpha-amanitin. However, CAT expression appeared to be modulated in the two forms of the parasite. Sequences 3' to the gene seemed to be important in this respect, as CAT activity in bloodstream forms was readily detectable only when the 3' region of a VSG cDNA was placed downstream of the CAT gene. Two separate VSG gene promoter sequences, both cloned from T. brucei AnTat 1.3A, were equally able to direct CAT expression, which suggests that there are a number of potential VSG gene promoters in the genome, although usually only one expression site is fully active at any one time.

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