A SINGLE EXPRESSION SITE WITH A CONSERVED LEADER SEQUENCE REGULATES VARIATION OF EXPRESSION OF THE PNEUMOCYSTIS-CARINII FAMILY OF MAJOR SURFACE GLYCOPROTEIN GENES

The major surface glycoprotein (MSG) of Pneumocystis carinii is encode d by a family of related but distinct genes distributed throughout the P. carinii genome, Previous reports of the genomic and mRNA MSG struc ture suggested that there was a highly conserved 5'-untranslated regio n and a highly variable translated region, In the current study, we de monstrate that there is a single expression site for MSG expression an d that different MSG genes are located downstream of this expression s ite, Isolation of a genomic clone containing the putative 5'-untransla ted region has demonstrated that there was a single base sequencing er ror in what was considered to be the untranslated region, The correcte d sequence reveals an extended open reading frame encoding a constant amino-terminal leader domain, with a typical signal peptide, for the M SG protein family, Since this constant amino-terminal domain is encode d by a single copy genomic sequence, a recombination/gene conversion-m ediated antigenic switching event is required to effect the known vari ability in expressed MSG sequences. Therefore, like some bacterial and protozoan pathogens, the opportunistic fungal pathogen P. carinii con tains a constant genomic site dedicated to MSG expression and a switch able downstream region for the variable part of the MSG gene family.