Same-Sex Mating in Cryptococcus?

Since Cryptococcus, like most club fungi (Basidiomycota), must mate to produce airborne spores, researchers have been faced with a mystery. "The unusual thing about C. neoformans and C. gattii is for the vast majority of the world you can only find [one sex]," says molecular geneticist James Fraser of the University of Queensland. The trouble is that, without mating, the yeast reproduces clonally, and individual cells typically are not tiny enough to infiltrate the lungs. So how can only a single sex of Cryptococcus infect people in the open air?

There's some surprising evidence to suggest that two strains of a single sex can, in fact, mate—a process which could produce spores small enough to become airborne. A 2005 study in Nature by Joseph Heitman's group at Duke University demonstrated that a unisexual population of C. neoformans could mate to produce airborne spores in the laboratory. ¹ Later that year, Fraser, Heitman, and colleagues published a genealogical analysis suggesting that the Vancouver Island fungus, C. gattii, had also undergone same-sex mating, a finding they suggested was key to its ability to expand into its new habitat on Vancouver Island. ²

Fraser and colleagues used multilocus sequence typing (MLST) at as many as 30 polymorphic loci to identify four discrete molecular types within C. gattii worldwide. Vancouver Island contained two of those four types, which the authors term a major form and a minor form, both of which were only present in a single sex. The major form, it turned out, was identical to a rare strain isolated from a human sputum sample in Seattle 30 years earlier, and to a sample collected from a San Francisco Eucalyptus camaldulensis tree in 1992. The minor form is identical to a widespread C. gattii strain from Australia and South America. The two strains were also closely related to each other, sharing 14 out of 30 alleles.

Fraser believes that the minor strain was one of two parents that begat the major strain and, possibly, its airborne spores. When they sequenced the sex-determining alleles in the two strains, they found that they were closely related but clearly different, suggesting that the major strain had inherited its sex-determining allele from an unknown parent of the same sex. Finding the second parent, Fraser admits, would have been the smoking gun, but he says it may no longer exist.

Karen Bartlett of the University of British Columbia remains skeptical. "It's a good theory," she says, "I'm not dissing it, I'm just not of the same opinion." Instead, she believes that C. gattii clones are hardy and small enough to become airborne and are able to infiltrate human lungs. For instance, she argues that the melanin-like pigments in Cryptococcus cells suggest that they have evolved to resist the high UV radiation encountered during airborne dispersal. Furthermore, her airborne samples have mostly fallen out in the upper three stages of the Andersen airborne sampler, indicating that the propagules range in size from 3.3m up to 7m or higher, far larger than the estimated 1-2m spore size. ³

It's certainly plausible for desiccated cells to evade the lung's ciliary defenses, Fraser says. Researchers have infected mice with Cryptococcus cells rather than spores in the lab, and Bartlett points out that spores are not required for airborne infection in other species: hyphae of Coccidioides immitis, which causes San Joaquin valley fever, dry out and break into fine particles which are readily inhaled. At least for now, this yeast's sex life will remain a mystery.

Clarification (posted December 3): When originally posted, the article implied that all fungi must mate to produce airborne spores. The text was referring to club fungi such as Cryptococcus. The text has been modified.