Eukaryotic Cell
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EC Accepts, published online ahead of print on 2 March 2007
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Eukaryotic Cell doi:10.1128/EC.00018-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Evolution of the mating-type locus: insights gained from the dimorphic primary fungal pathogens Histoplasma capsulatum, Coccidioides immitis and Coccidioides posadasii

James A. Fraser, Jason E. Stajich, Eric J. Tarcha, Garry T. Cole, Diane O. Inglis, Anita Sil, and Joseph Heitman*

School of Molecular and Microbial Sciences, University of Queensland, Brisbane, QLD 4072 Australia; Department of Plant and Microbial Biology, University of California Berkeley, Berkeley, CA 94720 USA; Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249 USA; Department of Microbiology and Immunology, University of California; San Francisco, San Francisco, CA 94143 USA; Departments of Molecular Genetics and Microbiology; Duke University Medical Center, Durham, NC 27710 USA

* To whom correspondence should be addressed. Email: heitm001{at}duke.edu.


   Abstract

Sexual reproduction of fungi is governed by the mating-type (MAT) locus, a specialized region of the genome encoding key transcriptional regulators that direct regulatory networks to specify cell identity and fate. Knowledge of MAT locus structure and evolution has been considerably advanced in recent years as a result of genomic analyses that enable definition of MAT loci sequences in many species as well as provide an understanding of the evolutionary plasticity of this unique region of the genome. Here, we extend this analysis to define the mating-type locus of three dimorphic primary human fungal pathogens - Histoplasma capsulatum, Coccidioides immitis, and Coccidioides posadasii - using genomic analysis, direct sequencing, and bioinformatics. These studies provide evidence that all three species possess heterothallic bipolar mating-type systems, with isolates encoding either an HMG domain or an {alpha} box transcriptional regulator. These genes are intact in all loci examined and have not been subject to loss or decay, providing evidence that the loss of fertility upon passage in H. capsulatum is not attributable to mutations at the MAT locus. These findings also suggest that an extant sexual cycle remains to be defined in both Coccidioides species, in accord with population genetic evidence. Based on these MAT sequences, a facile PCR test was developed that allows mating-type to be rapidly ascertained. Finally, these studies highlight the evolutionary forces shaping the MAT locus, revealing examples where flanking genes have been inverted, or subsumed and incorporated into an expanding MAT locus, allowing us to propose an expanded model for evolution of the MAT locus in the phylum Ascomycota.




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