Characterization of a protein acyl kinase from Caulobacter crescentus.
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Alkaline Phosphatase↗
Biomedical subjects
N Agabian
Publications and source records attributed to N Agabian.
Sequences homologous to variant antigen mRNA spliced leader in Trypanosomatidae which do not undergo antigenic variation.
Trypanosomes which parasitize mammals have evolved mechanisms to evade immune attack, such as the occupation of 'safe' intracellular sites (for example, Trypanosoma cruzi), or antigenic variation, exemplified by the salivarian trypanosomes (for example, Trypanosoma brucei). Antigenic variation is mediated by sequential expression of single variant surface glycoprotein (VSG) genes, and often involves transposition of the active gene. Every VSG transcript examined shares the same 5' terminal 35-nucleotide leader sequence. In T. brucei, this leader is encoded within a 1.4-kilobase unit tandemly reiterated to form a large array. It is hypothesized that this array is distantly linked to the expressed VSG gene and functions as a multiple promoter of VSG gene transcription, restricting transcription to that gene which, through genomic rearrangement, is placed downstream from the array. Leader and structural gene sequences are presumably juxtaposed by RNA splicing. Here we show that several trypanosomatids, both those which undergo antigenic variation (Trypanosoma congolense and Trypanosoma vivax) and those which do not (T. cruzi and Leptomonas collosoma), contain reiterated sequences homologous to the T. brucei spliced leader (SL). These results suggest that the SL, although utilized in VSG gene expression, is an ancestral sequence also used in the expression of other trypanosomatid genes.
Animals↗
Two mechanisms of expression of a predominant variant antigen gene of Trypanosoma brucei.
African trypanosomes evade the host immune response by periodically switching their variant surface glycoprotein (VSG) coat. The resulting, serologically distinct variant antigenic types (VATs) appear in a loosely ordered sequence and those arising early in infections are termed predominant VATs. VAT switching reflects the successive transcriptional activation of single VSG genes from a large repertoire. Activation of some VSG genes is accomplished by duplication of a previously silent basic copy (BC) gene and insertion of this expression linked copy (ELC) near a chromosomal telomere where is is expressed. However, other VSG genes, always located near a telomere, use a non-duplication activation ( NDA ) mechanism. We report here that the gene encoding the predominant IsTat 1.A VSG can be activated with or without duplication. Four of six independently derived clones activated the 1.A gene without gene duplication or detectable rearrangement. The other two contained an active 1.A ELC, possibly generated by a gene conversion extending to the end of the telomere. The ability to utilize both NDA and ELC mechanisms of gene activation and perhaps an alternative mechanism for gene duplication may account for the fact that VAT 1.A is the most predominant VAT of the IsTaR 1 serodeme .
Chromosome Mapping↗
Expression of a minichromosomal variant surface glycoprotein gene in Trypanosoma brucei.
African trypanosomes contain numerous variant surface glycoprotein (VSG) genes, but express only one at a time. When different VSG genes are activated by gene duplicative or non-duplicative mechanisms, antigenic variation occurs. Although transcriptionally inactive VSG genes can have either an intra-chromosomal or a telomeric location, all expressed VSG genes so far examined are telomeric. Some VSG genes are located on minichromosomes of approximately 100 kilobases (kb), but all those thus far described are transcriptionally inactive. We have found that the single copy of the IsTat 1.1 VSG gene in the IsTaR 1 serodeme has a telomeric location on a minichromosome when inactive. When it is activated, it is not duplicated and remains on a minichromosome. These data indicate that minichromosomes contain or can acquire all the DNA sequences necessary in cis for VSG gene expression and antigenic switching. Of several sequences associated with expressed VSG genes or their transcripts, only the 76-base pair (bp) repeat element was found in minichromosomal DNA. Variant antigenic types (VATs) which occurred immediately before and after VAT-1, expressed VSG genes located on larger chromosomes. Thus, different chromosomes can act as VSG gene expression sites.
Animals↗