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Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATalpha allele enhances filamentation.

Lin X, Huang JC, Mitchell TG, Heitman J - PLoS Genet. (2006)

Bottom Line: 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.MAC1 allelic differences contribute to phenotypic variation, and mac1Delta mutants exhibit defects in filamentation, melanin production, and high temperature growth.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.

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.

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Marker Distribution on Each ChromosomeThe distance between markers is proportional to the scale and is based on genetic distance calculated from physical distance (see Materials and Methods). The chromosome number is indicated at the top, the marker name is indicated on the right side for each chromosome, and the relative genetic position of each marker is indicated on the left side. The map was generated by WinQTL.
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pgen-0020187-g004: Marker Distribution on Each ChromosomeThe distance between markers is proportional to the scale and is based on genetic distance calculated from physical distance (see Materials and Methods). The chromosome number is indicated at the top, the marker name is indicated on the right side for each chromosome, and the relative genetic position of each marker is indicated on the left side. The map was generated by WinQTL.

Mentions: To map the genetic loci mediating variation in this quantitative trait involving hyphal elongation, we randomly selected 47 of the F2 isolates of each mating type (94 progeny total) and genotyped them, as well as the parental strains XL304α and XL187a. Development of a marker map for this population was necessary to identify QTLs contributing to the phenotypic variation by linkage analysis. The genomes of the closely related progenitor strains B3501α and B3502a (congenic with JEC21) are 50% identical [34], and the genomes of the F1 parental strains XL304α and XL187a are approximately 75% identical based on marker analysis (unpublished data). In addition to existing markers [35], we designed new polymorphic markers to genotype the mapping population. As shown in Figure 4, there were few markers on Chromosomes 1, 12, 13, and 14, and thus these may be uninformative unless QTLs are located close to the few available markers. In addition, Chromosome 10 was not subject to analysis because it was almost entirely monomorphic between the progenitor strains B3501α and B3502a [34,35]. Information about the number of markers and their chromosomal locations, the genotypic data, and the phenotypic value (i.e., average hyphal length at 17 d) are available in Table S3. These data were entered into the WinQTL program to perform a genome-wide linkage analysis.


Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATalpha allele enhances filamentation.

Lin X, Huang JC, Mitchell TG, Heitman J - PLoS Genet. (2006)

Marker Distribution on Each ChromosomeThe distance between markers is proportional to the scale and is based on genetic distance calculated from physical distance (see Materials and Methods). The chromosome number is indicated at the top, the marker name is indicated on the right side for each chromosome, and the relative genetic position of each marker is indicated on the left side. The map was generated by WinQTL.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1636697&req=5

pgen-0020187-g004: Marker Distribution on Each ChromosomeThe distance between markers is proportional to the scale and is based on genetic distance calculated from physical distance (see Materials and Methods). The chromosome number is indicated at the top, the marker name is indicated on the right side for each chromosome, and the relative genetic position of each marker is indicated on the left side. The map was generated by WinQTL.
Mentions: To map the genetic loci mediating variation in this quantitative trait involving hyphal elongation, we randomly selected 47 of the F2 isolates of each mating type (94 progeny total) and genotyped them, as well as the parental strains XL304α and XL187a. Development of a marker map for this population was necessary to identify QTLs contributing to the phenotypic variation by linkage analysis. The genomes of the closely related progenitor strains B3501α and B3502a (congenic with JEC21) are 50% identical [34], and the genomes of the F1 parental strains XL304α and XL187a are approximately 75% identical based on marker analysis (unpublished data). In addition to existing markers [35], we designed new polymorphic markers to genotype the mapping population. As shown in Figure 4, there were few markers on Chromosomes 1, 12, 13, and 14, and thus these may be uninformative unless QTLs are located close to the few available markers. In addition, Chromosome 10 was not subject to analysis because it was almost entirely monomorphic between the progenitor strains B3501α and B3502a [34,35]. Information about the number of markers and their chromosomal locations, the genotypic data, and the phenotypic value (i.e., average hyphal length at 17 d) are available in Table S3. These data were entered into the WinQTL program to perform a genome-wide linkage analysis.

Bottom Line: 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.MAC1 allelic differences contribute to phenotypic variation, and mac1Delta mutants exhibit defects in filamentation, melanin production, and high temperature growth.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.

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.

Show MeSH
Related in: MedlinePlus