Antigenic Variation by Positional Control of Major Surface Glycoprotein Gene Expression in Pneumocystis carinii

Major cell surface glycoproteins (MSGs) of Pneumocystis carinii play a crucial role in host-parasite interactions during P. carinii pneumocystosis in AIDS patients. Genes encoding MSGs are repeated and dispersed throughout the genome and are highly polymorphic. MSG gene expression was found to be mediated by a DNA element that was termed the upstream conserved sequence (UCS). The UCS element maps to a single chromosome, is attached to expressed MSG genes, and encodes the sequence found at the 5' ends of most MSG mRNAs. The UCS is not highly repeated, but P. carinii populations contain many different MSG genes attached to the UCS, suggesting that different organisms in the population have different MSG genes attached to the UCS. Such genetic heterogeneity may be generated by recombination between MSG genes at the UCS locus and one or more of the dozens of MSG genes located elsewhere in the genome.