title: Sixty alleles of the ALS7 open reading frame in Candida albicans: ALS7 is a hypermutable contingency locus.
abstract: The ALS (agglutinin-like sequence) gene family encodes proteins that play a role in adherence of the yeast Candida albicans to endothelial and epithelial cells. The proteins are proposed as virulence factors for this important fungal pathogen of humans. We analyzed 66 C. albicans strains, representing a worldwide collection of 266 infection-causing isolates, and discovered 60 alleles of the ALS7 open reading frame (ORF). Differences between alleles were largely caused by rearrangements of repeat elements in the so-called tandem repeat domain (21 different types occurred) and the VASES region (19 different types). C. albicans is diploid, and combinations of ALS7 alleles generated 49 different genotypes. ALS7 expression was detected in samples isolated directly from five oral candidosis patients. ORFs in the opposite direction contained within the ALS7 ORF were also transcribed in all strains tested. Isolates representing a more pathogenic general-purpose genotype (GPG) cluster of strains tended to have more tandem repeats than other strains. Two types of VASES regions were largely exclusive to GPG strains; the remaining types were largely exclusive to noncluster strains. Our results provide evidence that ALS7 is a hypermutable contingency locus and important for the success of C. albicans as an opportunistic pathogen of humans.
authors.affiliation: Institute of Molecular BioSciences, Massey University, Palmerston North, New Zealand.
authors.forename: Ningxin
authors.initials: N
authors.lastname: Zhang
authors.forename: Annette L
authors.initials: AL
authors.lastname: Harrex
authors.forename: Barbara R
authors.initials: BR
authors.lastname: Holland
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Fenton
authors.forename: Richard D
authors.initials: RD
authors.lastname: Cannon
authors.forename: Jan
authors.initials: J
authors.lastname: Schmid
mesh_terms: D000483:Alleles; D002176:Candida albicans / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000032:analysis; D013045:Species Specificity; D020080:Tandem Repeat Sequences / Q000235:genetics
chemical_list: C413711:ALS7 protein, Candida albicans; D005656:Fungal Proteins; D005819:Genetic Markers; D008562:Membrane Glycoproteins; D012333:RNA, Messenger