Unique telomeric expression site of major-surface-glycoprotein genes of Pneumocystis carinii

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.