Chapter 2 : Sex, , and the Evolution of Fungal Virulence

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While many fungi have a characterized sexual cycle, the pathogenic fungi represent a special example in which sexuality is uncommon and sexual mechanisms are unusual or cryptic. Given their evolutionary relationship to model organisms such as , it is striking that many species of pathogenic fungi have never been observed to mate in the laboratory despite population genetic evidence for recombining population structures. The study of the role of sexual cycles of pathogenic fungi therefore takes center stage, promising to reveal much about how these pathogenic microbes evolve, enabling infection of humans and continued adaptation to unique challenges, such as the advent of new therapeutic interventions. This chapter provides a summary of our current knowledge of the role of mating in pathogenic fungi and discusses future directions in this field. It reviews recent studies that shed light on the role of sex and the evolution of virulence in . was subjected to ongoing intraand interallelic gene conversion, and inversions that suppress recombination that may be driven by the high transposon content of the locus. The infectious particle of the primary pathogen is also an asexually produced structure, the arthroconidium. is a common fungal pathogen of humans that is often acquired early in life. The mechanisms by which organisms recombine their genomes to produce recombinant offspring are central to our understanding of how organisms evolve and adapt to new environments.

Citation: Fraser J, Heitman J. 2006. Sex, , and the Evolution of Fungal Virulence, p 13-33. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch2

Key Concept Ranking

Cryptococcus gattii
Genetic Recombination
Candida albicans
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Image of Figure 1.
Figure 1.

Fungal locus paradigms. Selection of mating partners during the sexual cycle is directed by bipolar mating systems in a wide variety of fungi. The budding yeast is an ascomycete with a locus of only 642 or 747 bp, encoding only one or two transcription factors. The related pathogenic ascomycete contains a locus over 10 times as large and, along with the components present in has an additional three or four genes. In contrast, the bipolar alleles of the pathogenic basidiomycete are over 140 times the size of their counterparts, containing more than 20 genes, many of which contribute to the sexual cycle including homeodomain transcription factors, pheromones and pheromone receptors, and other elements of the pheromone-activated MAPK cascade. The drawing is not to scale.

Citation: Fraser J, Heitman J. 2006. Sex, , and the Evolution of Fungal Virulence, p 13-33. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch2
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Image of Figure 2.
Figure 2.

Association of mating type with virulence in . Why are isolates so common in the clinical setting? For serotype D, studies with various isolates and the JEC20-JEC21 congenic strain pair showed that in this variety the α mating type is associated with increased virulence ( ). However, in the more clinically relevant serotype A, the KN99-KN99α congenic strain pair have equivalent virulence to each other in a murine inhalation assay ( ). The role of mating type in virulence may therefore differ between the less virulent serotype D strains and the most common pathogenic variety, serotype A.

Citation: Fraser J, Heitman J. 2006. Sex, , and the Evolution of Fungal Virulence, p 13-33. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch2
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Image of Figure 3.
Figure 3.

The Vancouver Island isolates of are clonal. (A) Comparison of isolates using the (GACA) random amplification of polymorphic DNA (RAPD) fingerprinting method shows that isolates from around the world exhibit a high degree of variation. In contrast, clinical, veterinary, and environmental isolates from the Vancouver Island outbreak all appear to be clonal. (B) PCR of the α-specific gene reveals that the isolates from the Vancouver Island outbreak are exclusively of the α mating type. M, marker.

Citation: Fraser J, Heitman J. 2006. Sex, , and the Evolution of Fungal Virulence, p 13-33. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch2
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Image of Figure 4.
Figure 4.

The locus of filamentous ascomycetes. The genomic revolution has allowed the identification of the locus from a large variety of ascomycetous fungi based on homology and synteny, even in the absence of a strain of the opposite mating type. Based on the nomenclature system proposed by Turgeon and Yoder ( ), most of these can be classified into one of two types. idiomorphs contain an α-box-domain-encoding homeobox gene, as is seen in the genome sequence of idiomorphs contain an HMG-domain-encoding gene, as seen in the genome sequences of , and . Homothallism can arise from a wide variety of events—in the saprophyte , this appears to have arisen by a translocation event leading to the presence of both idiomorphs in the haploid genome, as suggested by synteny with the adjacent orthologs of (encoding a protein involved in cytoskeleton assembly) and (encoding DNA lyase). The drawing is not to scale.

Citation: Fraser J, Heitman J. 2006. Sex, , and the Evolution of Fungal Virulence, p 13-33. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch2
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Image of Figure 5.
Figure 5.

Variations on a common locus structure in related ascomycetes. The model budding yeast is a homothallic ascomycete with a bipolar mating system. Cells have the ability to undergo mating-type switching in response to cleavage by the Ho endonuclease, allowing the active cassette to be replaced with the silent cassette of the opposite mating type. The closely related pathogenic ascomycetous yeast bears a similar system; however, one of the silent cassettes resides on another chromosome. While the silent cassettes usually contain the alleles shown here, they have been observed to encode either or α at lower frequencies. The more distantly related pathogen also has a bipolar system but lacks silent cassettes or the Ho endonuclease and does not undergo mating-type switching. The drawing is not to scale.

Citation: Fraser J, Heitman J. 2006. Sex, , and the Evolution of Fungal Virulence, p 13-33. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch2
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