Pneumocystis carinii Subtelomeres

Abstract

Pneumocystis carinii is a yeast-like fungus that dwells exclusively in rats, where it is subjected to the host immune response. Immune pressure is countered by three subtelomeric gene families that generate antigenic diversity in populations of P. carinii. Members of the three gene families are grouped together in tandem arrays that appear to have been generated by recombination and modified by further recombination events after array formation. One of these gene families, MSG, encodes various forms of a major surface glycoprotein. In a given P. carinii organism, all but one of the members of the MSG gene family appear to be transcriptionally silent. The expressed MSG gene is adjacent to a unique locus (the expression site). Different MSG genes can occupy the expression site, suggesting that recombination can take a gene from a pool of silent donors and install it at the expression site, thereby extinguishing transcription of the previous expression site resident, activating transcription of the newly installed MSG gene, and changing the surface of the microbe. Switching at the expression site is probably facilitated by the subtelomeric locations of expressed and silent MSG genes. A second subtelomeric gene family, MSR, is not strictly regulated at the transcriptional level, but may contribute to phenotypic diversity via high-frequency frameshifting caused by coding poly(G) tracts in some MSR genes.