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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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Different Responses to Copper in Melanin Production and Filamentation among the Mapping PopulationCells were cultured on L-DOPA medium with or without addition of 50 μM copper sulfate.(A) Differences in melanin production. The upper panel shows the melanin production on medium supplemented with copper and the lower panel without copper addition.(B) Differences in filamentation. The progeny in the left bottom corner of the plate in red rectangles in (A) are shown. The upper panel shows filamentation in the medium without copper and the lower panel with copper addition.
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pgen-0020187-g010: Different Responses to Copper in Melanin Production and Filamentation among the Mapping PopulationCells were cultured on L-DOPA medium with or without addition of 50 μM copper sulfate.(A) Differences in melanin production. The upper panel shows the melanin production on medium supplemented with copper and the lower panel without copper addition.(B) Differences in filamentation. The progeny in the left bottom corner of the plate in red rectangles in (A) are shown. The upper panel shows filamentation in the medium without copper and the lower panel with copper addition.

Mentions: Because the overlapping QTL for three different traits localized to a region on Chromosome 7 (Figure 9), we sought to identify candidate QTGs in this region that could regulate one or more traits. As the region above the threshold LOD on Chromosome 7 is large (~150 kb), we narrowed our search based on two criteria. First, we screened for genes with DNA polymorphisms resulting in amino acid substitutions between the two progenitor strains, B3501α and B3502a. These genes are likely QTG candidates, although polymorphisms in regulatory elements might also be responsible. Second, because copper homeostasis is intimately linked to melanization in C. neoformans [56], and the QTL on Chromosome 7 is the main single locus responsible for the variation in melanin production (Figure 9), we tested the response of the mapping population to the addition of copper. The addition of copper to the media caused changes in both melanin production and filamentation to different degrees among the mapping population (Figure 10), suggesting that copper regulation might play pleiotropic roles. Therefore, we searched for genes whose products might control copper responses.


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)

Different Responses to Copper in Melanin Production and Filamentation among the Mapping PopulationCells were cultured on L-DOPA medium with or without addition of 50 μM copper sulfate.(A) Differences in melanin production. The upper panel shows the melanin production on medium supplemented with copper and the lower panel without copper addition.(B) Differences in filamentation. The progeny in the left bottom corner of the plate in red rectangles in (A) are shown. The upper panel shows filamentation in the medium without copper and the lower panel with copper addition.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-0020187-g010: Different Responses to Copper in Melanin Production and Filamentation among the Mapping PopulationCells were cultured on L-DOPA medium with or without addition of 50 μM copper sulfate.(A) Differences in melanin production. The upper panel shows the melanin production on medium supplemented with copper and the lower panel without copper addition.(B) Differences in filamentation. The progeny in the left bottom corner of the plate in red rectangles in (A) are shown. The upper panel shows filamentation in the medium without copper and the lower panel with copper addition.
Mentions: Because the overlapping QTL for three different traits localized to a region on Chromosome 7 (Figure 9), we sought to identify candidate QTGs in this region that could regulate one or more traits. As the region above the threshold LOD on Chromosome 7 is large (~150 kb), we narrowed our search based on two criteria. First, we screened for genes with DNA polymorphisms resulting in amino acid substitutions between the two progenitor strains, B3501α and B3502a. These genes are likely QTG candidates, although polymorphisms in regulatory elements might also be responsible. Second, because copper homeostasis is intimately linked to melanization in C. neoformans [56], and the QTL on Chromosome 7 is the main single locus responsible for the variation in melanin production (Figure 9), we tested the response of the mapping population to the addition of copper. The addition of copper to the media caused changes in both melanin production and filamentation to different degrees among the mapping population (Figure 10), suggesting that copper regulation might play pleiotropic roles. Therefore, we searched for genes whose products might control copper responses.

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