The human pathogenic Cryptococcus neoformans species complex are agents of a common AIDS-defining disease, which causes about 181,000 deaths each year. There are several specific features distinguishing this species from other fungi, including the presence of a polysaccharide capsule and melanin pigment production, both of which contribute to its virulence. A large number of studies about this pathogen used two model strains JEC20 and JEC21. In these studies, these two strains are assumed to be “isogenic”, differ only at the mating type region. Consequently, their phenotypic differences, including virulence, have been attributed to this region. Here, we applied second-generation sequencing and bioinformatics tools to identify sequence polymorphisms between the two genomes. Beside the Mating Type locus, two other regions were found to contain high frequencies of SNPs. To further understand the effects of these loci on the phenotypic differences, four phenotyping assays (mating ability, melanin pigment production, capsule formation, and high temperature growth ability) were conducted on the recombinant progeny obtained from the cross between JEC20 and JEC21. In addition, genomic sequences of these progeny were obtained to identify the complete distributions of other SNPs among the strains. Finally, we identified several novel SNPs contributing to virulence-related traits in this species, which suggest that caution should be placed in attributing phenotypic differences to specific genomic regions in “isogenic” strains derived from classical breeding experiments. / Thesis / Master of Science (MSc) / Cryptococcosis is a globally distributed infection that is prevalent among immune-compromised individuals, such as HIV/AIDS patients. This disease can be attributed to a group of opportunistic fungal pathogens – Cryptococcus neoformans species complex. During the past century, significant resources have been put in an effort to understand its ecology, evolution, life cycle, pathogenesis and virulence factors, and molecular and cellular processes. Most of the laboratory-based studies have relied on two model strains assumed to differ only at the mating type locus. My thesis investigated this assumption and found there are several additional significant genetic differences between these two strains and that such differences contribute to the observed phenotypic differences between them. My results highlight the complexity of genotype-phenotype relationships and the continued evolution of strains even in lab environments in C. neoformans.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22202 |
| Date | 11 1900 |
| Creators | Hua, Wenjing |
| Contributors | Xu, Jianping, Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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