Abstract
Author SummaryAneuploidy refers to increases or decreases in the copy number of individual chromosomes (rather than of the entire haploid or diploid genome). In humans, aneuploidy is well known to be deleterious, causing genetic disorders such as Down syndrome (trisomy 21), and frequently occurring during mitosis in the genesis of cancer. By contrast, aneuploidy in fungi can be advantageous, conferring antifungal drug resistance and enabling rapid adaptive evolution. Cryptococcus neoformans is a globally distributed human pathogen that often infects patients with compromised immunity. It accounts for significant morbidity and mortality associated with HIV/AIDS and is linked to more than one million infections and >600,000 deaths per year world-wide. Although C. neoformans has a defined heterosexual cycle involving a and α cells, more than 99% of clinical and environmental isolates are α. Interestingly, C. neoformans α cells undergo α-α unisexual reproduction to generate diploid intermediates and infectious haploid spores. Sex is costly, though, and the question therefore arises as to why C. neoformans would undergo selfing unisexual, meiotic reproduction as opposed to more efficient asexual, mitotic reproduction. We show here that unisexual, meiotic reproduction in C. neoformans results in aneuploidy, creating advantageous genetic diversity de novo.
Highlights
Aneuploidy, a condition in which cells have an abnormal number of chromosomes, can cause deleterious effects in organisms throughout the eukaryotic tree of life
Cryptococcus neoformans is a globally distributed human pathogen that often infects patients with compromised immunity. It accounts for significant morbidity and mortality associated with HIV/AIDS and is linked to more than one million infections and .600,000 deaths per year world-wide
We show here that unisexual, meiotic reproduction in C. neoformans results in aneuploidy, creating advantageous genetic diversity de novo
Summary
Aneuploidy, a condition in which cells have an abnormal number of chromosomes, can cause deleterious effects in organisms throughout the eukaryotic tree of life. Aneuploidy can be advantageous in fungi by conferring antifungal drug resistance and enabling rapid adaptive evolution. Mutations in a deubiquitinating enzyme of S. cerevisiae, which arose during the evolution of an aneuploid isolate, leads to improved proliferation of many aneuploid strains, likely by promoting degradation of aberrant proteins produced in perturbed stoichiometric ratios [11]. Rancanti et al found that aneuploidy facilitated adaptive evolution in yeast cells lacking the conserved motor protein Myo involved in cytokinesis [12]. It has been found that chromosomal duplication may confer a selective advantage to S. cerevisiae under stress conditions by promoting genomic instability
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