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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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Expression Profile of Genes in the MAT Locus Is Similar between a and αRNA from strain XL304α and XL187a cultured on V8 medium for 24 h was hybridized against each other on a 70-mer genome array after labeling with fluorescent dyes. The expression level was normalized across the genome, and the average of three independent replicates for the genes in the MAT locus that are on the array is shown. The a alleles are indicated as open bars and the α alleles as solid bars. Because of the high conservation between the a and α alleles for the ETF1 and MYO2 genes, instead of separate expression levels for each allele, the expression ratio of the two alleles is used and indicated as hatched bars. Because the ratio of ETF1 and MYO2 is close to 1, it indicates that the two are expressed at equivalent levels in the two cell types.
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pgen-0020187-g007: Expression Profile of Genes in the MAT Locus Is Similar between a and αRNA from strain XL304α and XL187a cultured on V8 medium for 24 h was hybridized against each other on a 70-mer genome array after labeling with fluorescent dyes. The expression level was normalized across the genome, and the average of three independent replicates for the genes in the MAT locus that are on the array is shown. The a alleles are indicated as open bars and the α alleles as solid bars. Because of the high conservation between the a and α alleles for the ETF1 and MYO2 genes, instead of separate expression levels for each allele, the expression ratio of the two alleles is used and indicated as hatched bars. Because the ratio of ETF1 and MYO2 is close to 1, it indicates that the two are expressed at equivalent levels in the two cell types.

Mentions: To distinguish between the two hypotheses (allele-specific expression or allele-specific function), the expression level of genes in the MAT locus at 24 h post-inoculation on V8 medium was examined for the parental strains XL304α and XL187a, which display phenotypic difference in hyphal growth. As shown in Figure 7, subtle differences could exist in the expression level of some genes, but the overall expression profile of the a or α alleles of the genes in the MAT locus was similar. Thus, the steady state expression levels of genes in the MAT locus is not likely to be responsible for the phenotypic variation observed for a and α isolates in this inbred population, although it remains possible there could be expression differences at the protein level not detected by this approach. Therefore, we favor the hypothesis that differences in the allelic composition likely account for the enhanced hyphal elongation observed with α isolates.


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)

Expression Profile of Genes in the MAT Locus Is Similar between a and αRNA from strain XL304α and XL187a cultured on V8 medium for 24 h was hybridized against each other on a 70-mer genome array after labeling with fluorescent dyes. The expression level was normalized across the genome, and the average of three independent replicates for the genes in the MAT locus that are on the array is shown. The a alleles are indicated as open bars and the α alleles as solid bars. Because of the high conservation between the a and α alleles for the ETF1 and MYO2 genes, instead of separate expression levels for each allele, the expression ratio of the two alleles is used and indicated as hatched bars. Because the ratio of ETF1 and MYO2 is close to 1, it indicates that the two are expressed at equivalent levels in the two cell types.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-0020187-g007: Expression Profile of Genes in the MAT Locus Is Similar between a and αRNA from strain XL304α and XL187a cultured on V8 medium for 24 h was hybridized against each other on a 70-mer genome array after labeling with fluorescent dyes. The expression level was normalized across the genome, and the average of three independent replicates for the genes in the MAT locus that are on the array is shown. The a alleles are indicated as open bars and the α alleles as solid bars. Because of the high conservation between the a and α alleles for the ETF1 and MYO2 genes, instead of separate expression levels for each allele, the expression ratio of the two alleles is used and indicated as hatched bars. Because the ratio of ETF1 and MYO2 is close to 1, it indicates that the two are expressed at equivalent levels in the two cell types.
Mentions: To distinguish between the two hypotheses (allele-specific expression or allele-specific function), the expression level of genes in the MAT locus at 24 h post-inoculation on V8 medium was examined for the parental strains XL304α and XL187a, which display phenotypic difference in hyphal growth. As shown in Figure 7, subtle differences could exist in the expression level of some genes, but the overall expression profile of the a or α alleles of the genes in the MAT locus was similar. Thus, the steady state expression levels of genes in the MAT locus is not likely to be responsible for the phenotypic variation observed for a and α isolates in this inbred population, although it remains possible there could be expression differences at the protein level not detected by this approach. Therefore, we favor the hypothesis that differences in the allelic composition likely account for the enhanced hyphal elongation observed with α isolates.

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