A team of researchers led by Professor Joseph Heitman has discovered procreation between genetically identical fungi Cryptococcus neoformans can result in genetic changes and diversity in their offspring, lending insight into how they can evolve to cause and spread disease. These results are published 10 September 2013 in the open access journal PLOS Biology.
"These studies turn our view of the functions of sex by 180 degrees and reveal that sex doesn't just mix up already existing genetic diversity, but can actually create it from scratch," said Professor Heitman, Chair of Department of Molecular Genetics and Microbiology at Duke University School of Medicine.
The fungi Cryptococcus neoformans is a global pathogen that primarily infects individuals with compromised immune systems, such as HIV/AIDS patients. It causes more than 600,000 deaths a year from cryptococcal pneumonia and meningoencephalitis, accounting for a third of all AIDS-related deaths.
Researchers have been interested in the sexual cycle of Cryptococcus because it is the only way this fungal pathogen produces spores to infect its host. Though it has two mating types -"a" and "alpha" - the vast majority of the fungi found in nature are of the alpha variety. A previous study by Heitman and Xiaorong Lin showed that Cryptococcus engaged in a phenomenon known as unisexual reproduction: sex involving fungi of the same mating type.
"That was a big mystery because if there are two identical genomes coming together, the end product should be the same as if the fungi had just cloned itself through asexual reproduction," said Heitman.
Heitman and his colleagues, Min Ni and Marianna Feretzaki, grew the microbe in two different ways - one where it underwent asexual reproduction, the other where it underwent unisexual reproduction. They then compared the offspring of these reproductive cycles to each other and to the starting parent.
The offspring of asexual reproduction were essentially clones, looking identical to each other and the parent. However, some of the offspring of unisexual reproduction differed, both in terms of genetic makeup and behavior. These differences were due to a genetic change called aneuploidy: having more than the normal number of DNA-packaging chromosomes.
The researchers discovered that aneuploidy could lead to beneficial, neutral or detrimental changes in the fitness of the offspring. Offspring with an extra copy of chromosome 9 or 10 became drug resistant and were able to outcompete their parent when subjected to antifungal treatment.
When used to infect animal models, the aneuploid offspring proved just as virulent as the parent, suggesting new properties (drug resistance) and old ones (virulence) could be combined.
"An interesting feature of aneuploidy is it can be temporary," said Heitman. "If at some point it stops being beneficial or adaptive, the fungi can lose the chromosome just as easily as they gained it. In fact, we showed that if we took the aneuploid offspring and let them lose their extra chromosomes, they also lose their new properties and go back to behaving just like their parent did."
The key finding, he said, "illustrates how unisexual reproduction introduces limited genetic diversity in clonal populations already well adapted to an environment, which may drive outbreaks of drug resistant pathogenic microbes"
Funding: MN was supported by the Molecular Mycology and Pathogenesis Training Program T32-AI52080 from the NIH/NIAID. This work was supported by NIH/NIAID grants R37 AI39115-15 and R01 AI50113-10. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Citation: Ni M, Feretzaki M, Li W, Floyd-Averette A, Mieczkowski P, et al. (2013) Unisexual and Heterosexual Meiotic Reproduction Generate Aneuploidy and Phenotypic Diversity De Novo in the Yeast Cryptococcus neoformans. PLoS Biol 11(9): e1001653. doi:10.1371/journal.pbio.1001653
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Related image for press use: spores and basidia
Professor Joseph Heitman
Duke University Medical Center
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