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Unique telomeric expression site of major-surface-glycoprotein genes of Pneumocystis carinii
1Department of Tumor Biology, University of Tokyo, Japan.
Abstract:
Major cell surface glycoproteins (MSG) of Pneumocystis carinii play a crucial role in the host-parasite interactions involved in P. carinii pneumonia in AIDS patients. Genes encoding MSGs are repeated, highly polymorphic, and distributed among all of the 14-15 chromosomes. Here we show, by BAL-31 exonuclease cleavage and DNA cloning experiments, that the unique expression site (previously termed UCS) of MSG genes located in the 500-kb chromosome is telomeric. The 11-kb genomic UCS fragment isolated and sequenced in this study contained one MSG coding sequence (termed msg105), subtelomeric repetitive sequences and telomere-specific tandem repeats of TTAGGG oriented 5' to 3' towards the DNA end. Despite the N-terminal polymorphism, the C-terminal one-third sequence of MSG105 was identical to one of the known MSG-cDNAs, suggesting homologous recombination within the MSG coding sequences. These features closely resemble the Variant Surface Glycoprotein system of the protozoan parasite Trypanosoma brucei, suggesting that the genetic heterogeneity of MSGs is generated by recombination between the UCS expression site and multiple MSG genes by means of reciprocal exchange or gene conversion.
Insights
Major cell surface glycoproteins (MSG) in Pneumocystis carinii are located at a telomeric expression site. Genetic heterogeneity of these MSGs is generated by recombination, similar to Trypanosoma brucei.
Area of Science:
- Microbiology
- Parasitology
- Molecular Genetics
Background:
- Major cell surface glycoproteins (MSG) are critical for Pneumocystis carinii interactions during pneumonia in AIDS patients.
- MSG genes are polymorphic, repeated, and found across all P. carinii chromosomes.
Purpose of the Study:
- To identify the genomic location and structure of the unique expression site (UCS) for MSG genes.
- To elucidate the mechanisms generating genetic heterogeneity in P. carinii MSGs.
Main Methods:
- BAL-31 exonuclease cleavage and DNA cloning experiments were employed.
- Genomic DNA fragments from the UCS were isolated, sequenced, and analyzed.
Main Results:
- The UCS for MSG genes was localized to the telomeric region of a 500-kb chromosome.
- The 11-kb UCS fragment contained an MSG coding sequence (msg105), subtelomeric repeats, and telomere-specific repeats.
- Homologous recombination within MSG coding sequences was suggested by sequence identity.
Conclusions:
- The telomeric location of the UCS facilitates genetic variation in P. carinii MSGs.
- Recombination between the UCS and MSG genes, possibly via reciprocal exchange or gene conversion, generates MSG heterogeneity.
- This mechanism resembles the Variant Surface Glycoprotein system in Trypanosoma brucei.