title: Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATalpha allele enhances filamentation.
abstract: Cryptococcus neoformans is a fungal human pathogen with a bipolar mating system. It undergoes a dimorphic transition from a unicellular yeast to hyphal filamentous growth during mating and monokaryotic fruiting. The traditional sexual cycle that leads to the production of infectious basidiospores involves cells of both alpha and a mating type. Monokaryotic fruiting is a modified form of sexual reproduction that involves cells of the same mating type, most commonly alpha, which is the predominant mating type in both the environment and clinical isolates. However, some a isolates can also undergo monokaryotic fruiting. To determine whether mating type and other genetic loci contribute to the differences in fruiting observed between alpha and a cells, we applied quantitative trait loci (QTL) mapping to an inbred population of F2 progeny. We discovered that variation in hyphal length produced during fruiting is a quantitative trait resulting from the combined effects of multiple genetic loci, including the mating type (MAT) locus. Importantly, the alpha allele of the MAT locus enhanced hyphal growth compared with the a allele. Other virulence traits, including melanization and growth at 39 degrees C, also are quantitative traits that share a common QTL with hyphal growth. The Mac1 transcription factor, encoded in this common QTL, regulates copper homeostasis. MAC1 allelic differences contribute to phenotypic variation, and mac1Delta mutants exhibit defects in filamentation, melanin production, and high temperature growth. Further characterization of these QTL regions will reveal additional quantitative trait genes controlling biological processes central to fungal development and pathogenicity.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Lin
authors.forename: Johnny C
authors.initials: JC
authors.lastname: Huang
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Mitchell
authors.forename: Joseph
authors.initials: J
authors.lastname: Heitman
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D015825:Chromosomes, Fungal / Q000235:genetics; D003300:Copper / Q000494:pharmacology; D003455:Cryptococcus neoformans / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity*; D048690:Fruiting Bodies, Fungal / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D049770:Genes, Mating Type, Fungal / Q000235:genetics*; D005819:Genetic Markers; D014644:Genetic Variation; D025301:Hyphae / Q000166:cytology / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development*; D008543:Melanins / Q000096:biosynthesis; D008969:Molecular Sequence Data; D040641:Quantitative Trait Loci; D013696:Temperature; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D005819:Genetic Markers; D008543:Melanins; D003300:Copper