Deciphering the Model Pathogenic Fungus Cryptococcus Neoformans

The Cryptococcus neoformans genome comprises 20 Mb of DNA over 14 chromosomes, encoding 6,574 predicted genes. Unusual features include high levels of alternatively spliced genes (4.3%) and antisense messages (0.8%).The genome contains many predicted transposons (5% of nucleotide content), but these are inactive most of the time. Nevertheless, such repetitive elements enable genome rearrangements, both in small regions to cause inversions, such as in the mating-type locus, and in larger regions to cause DNA-duplication events across chromosomes.Development of research tools (for genetics, targeted and random mutagenesis, gene expression profiling and virulence assays) makes C. neoformans the most amenable human pathogenic fungus to study.The maintenance of virulence in the fungus depends on interactions with the environment, rather than the human host. Environmental hosts can include microorganisms like amoeba or nematodes, insects or small mammals.It is still unclear whether humans are infected by C. neoformans yeast cells or sexual basidiospores. The fungus is heterothallic, but can also undergo sexual recombination between strains of a single mating-type identity, suggesting a means of generating spores in the absence of an opposite mating partner.Mating-type specificity is controlled by a region of the genome (the MAT locus) that is unusually large (∼100 kb) compared with other fungi. Comparison of this sequence in three divergent strains suggests that the region evolved from the fusion of a tetrapolar mating system into a bipolar system.The ability to sense and respond to the environment is mediated by signal-transduction pathways that are conserved between C. neoformans and other fungi; however, most of the upstream receptors and downstream transcriptional regulators are divergent, as is the crosstalk between the pathways. In addition, the genome contains many uncharacterized signal-transduction proteins.