Same-sex mating discovered in an infectious fungus

An infectious fungus has been found to defy the most basic tenet of sexual reproduction - that successful mating requires
individuals of the opposite sex, according to Howard Hughes Medical Institute researchers at Duke University Medical Center.



In the April 21, 2005, issue of Nature, the researchers reported that, in the infectious fungus Cryptococcus neoformans,
members of the same "sex" can mate and produce offspring. Infection with the fungus can prove life-threatening in humans, and
the findings might improve understanding of the fungal biology that underlies the infectious process, the researchers said.
Discovery of the same-sex mating might also help elucidate basic principles governing the evolution of sex, they said.



"Sex is generally beneficial as a means to produce offspring with different gene combinations that can adapt more rapidly to
new environments," said HHMI investigator Joseph Heitman, M.D., Ph.D., of Duke, senior author of the study.


"The findings suggest for the first time that the fungus has developed a novel type of sexual cycle, allowing sexual
reproduction between members of the same mating type," he added. "That ability might confer an advantage for the fungus
because patients infected with it predominantly harbor a single mating type, reducing the possibility of normal fungal sexual
reproduction."


The potentially life-threatening fungus C. neoformans invades the central nervous system to cause disease, most commonly in
immune-compromised patients such as organ transplant recipients and cancer patients -- whose immune systems are crippled by
immunosuppressive drugs or chemotherapy -- and people with HIV/AIDS. The fungus' global importance as a health threat has
therefore risen in parallel with the increased use of such therapies and with the worldwide HIV/AIDS pandemic.


In plants and animals, sexual identity is governed by sex chromosomes. In fungi, however, sexual identity is determined by
so-called "mating type loci," genes arranged contiguously, but which typically do not span an entire chromosome. C.
neoformans exists in two mating types, a and alpha, determined by a single genetic region, or locus.


Most fungal isolates taken from people infected by C. neoformans are of the alpha mating type, said study lead author and
post-doctoral fellow Xiaorong Lin, Ph.D., also of Duke.


"Organisms, including fungi, usually exist in an approximately one-to-one sex ratio," Lin said. "Yet in Cryptococcus
neoformans, one mating type predominates, leaving them with apparently few chances to mate. It's been a mystery."


In 1996, another group discovered that those alpha isolates could undergo fruiting and produce spores, a process that
resembles sexual reproduction. However, researchers thought that the unisexual fruiting occurred strictly through the asexual
division of cells into identical clones, Heitman said.















That left scientists with a conundrum. C. neoformans has a defined sexual cycle involving both mating types. "Yet, how can
sexual reproductive potential be maintained in an organism with a largely unisexual population structure?" Heitman asked.
"The fruiting of alpha strains provided a clue."


In their laboratory experiments, the researchers found that, rather than being an asexual process, the hallmarks of mating
occur during fruiting of alpha isolates. Unisexual fruiting involves the fusion of cells followed by meiosis, enabling
genetic exchange between members of the same sex, they reported.


Meiosis is the process whereby cells divide into two "haploid" cells, each with half the number of chromosomes. Unlike
diploid animals and plants, C. neoformans normal state is haploid, Heitman explained.


Furthermore, the team showed, strains lacking components required for mating -- including pheromones, pheromone receptors and
other genes with known roles in mating -- exhibited a defect in fruiting.


The newly described mating strategy might allow a single mating strain to expand rapidly by cell division, yet retain its
ability to generate diversity by undergoing sex, said Heitman. That diversity might provide an advantage when faced with new
environmental challenges, he said.


While the findings have no immediately obvious clinical implications, Heitman said, "the more we know about the biological
cause of any disease, the better positioned we are to develop cost-effective diagnostic or therapeutic interventions."



The fungal strategy may also contribute to scientists' general understanding of the conditions that favor evolutionary
transitions between self-fertilization and sexual reproduction among unrelated individuals, known to occur in the fungal,
plant and even animal kingdoms, the researchers said.


Christina Hull, now at the University of Wisconsin, Madison, also contributed to the research. The work was supported by the
National Institute of Allergy and Infectious Disease, the Damon Runyon Cancer Research Fellowship and the Burroughs Wellcome
Fund.


Contact: Kendall Morgan

kendall.morganduke

919-660-1306

Duke University Medical Center

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