title: A single expression site with a conserved leader sequence regulates variation of expression of the Pneumocystis carinii family of major surface glycoprotein genes.
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.
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco 94143-0626, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Edman
authors.forename: T W
authors.initials: TW
authors.lastname: Hatton
authors.forename: M
authors.initials: M
authors.lastname: Nam
authors.forename: R
authors.initials: R
authors.lastname: Turner
authors.forename: Q
authors.initials: Q
authors.lastname: Mei
authors.forename: C W
authors.initials: CW
authors.lastname: Angus
authors.forename: J A
authors.initials: JA
authors.lastname: Kovacs
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015825:Chromosomes, Fungal; D017124:Conserved Sequence; D005656:Fungal Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D014644:Genetic Variation; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D011010:Pneumocystis / Q000235:genetics* / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000096:biosynthesis* / Q000737:chemistry; D051381:Rats; D012689:Sequence Homology, Nucleic Acid
chemical_list: D005656:Fungal Proteins; D008562:Membrane Glycoproteins; D021382:Protein Sorting Signals; C077556:GPA protein, Pneumocystis carinii sp.