A Single Expression Site with a Conserved Leader Sequence Regulates Variation of Expression of thePneumocystis cariniiFamily of Major Surface Glycoprotein Genes

Publisher Website
Google Scholar
Abstract
The major surface glycoprotein (MSG) of Pneumocystis carinii is encoded by a family of related but distinct genes distributed throughout the P. carinii genome. Previous reports of the genomic and mRNA MSG structure suggested that there was a highly conserved 5′-untranslated region and a highly variable translated region. In the current study, we demonstrate that there is a single expression site for MSG expression and that different MSG genes are located downstream of this expression site. Isolation of a genomic clone containing the putative 5′-untranslated region has demonstrated that there was a single base sequencing error in what was considered to be the untranslated region. The corrected sequence reveals an extended open reading frame encoding a constant amino-terminal leader domain, with a typical signal peptide, for the MSG protein family. Since this constant amino-terminal domain is encoded by a single copy genomic sequence, a recombination/gene conversion-mediated antigenic switching event is required to effect the known variability in expressed MSG sequences. Therefore, like some bacterial and protozoan pathogens, the opportunistic fungal pathogen P. carinii contains a constant genomic site dedicated to MSG expression and a switchable downstream region for the variable part of the MSG gene family.