Same-sex mating discovered in an infectious fungus

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Same-sex mating discovered in an infectious fungus21 Apr 2005

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 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 ph 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.

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

kendall.morgan@...

919-660-1306

Duke University Medical Center

http://www.dukemednews.org