Population genetics and genomics of Coccidioides immitis and Coccidioides posadasii.

摘要

The goal of my dissertation research is to elucidate the population structure of two understudied but increasingly important fungal pathogens of humans. Coccidioides immitis and C. posadasii cause the disease coccidioidomycosis (Valley fever). These fungi occur in the soil of the desert regions of North and South America. Although studied for over 100 years, the primary host, ecological niche, and sexual cycle of Coccidioides spp. still remain unknown. Understanding the population structure of these fungi will permit identification of fundamental aspects of their ecology and allow researchers to identify potential hosts. Assessing genotypic diversity of pathogens is one step to understanding the population structure and evolutionary potential of organisms, and is the focus of this dissertation. The first appendix focuses on developing and evaluating methods to obtain environmental samples, and comparison of genotypes found in soil vs. human patients. Direct inoculation of mice proved to be the most reliable method of obtaining environmental strains. Environmental isolates from Tucson group with Arizona patient isolates. Comparing genotypes of human, environmental and nonhuman host strains of Coccidioides may help to determine if gene flow occurs over long distances and provide some indication of the population structure of C. posadasii in the environment, and is the focus of the second appendix. Finally, whole-genome sequencing and resequencing has been completed for 20 strains of C. immitis and C. posadasii. The resulting data provide greater insight into variation between and within species. In particular, the final appendix provides evidence for hybridization and gene flow between species. Data show that a region of C. posadasii origin is found at a higher frequency among the C. immitis southern California and Mexico patient isolates, and is found rarely among patient isolates from the San Joaquin Valley. Of particular interest is the fact that there is a conserved border region for all instances of introgression, and the gene immediately adjacent to this border is a metalloproteinase gene. Together these studies provide insight into the population biology of two human pathogenic fungi: gene flow is limited between species and populations, but genetic exchange occurs at all levels.