| The study of natural variation has been of long-standing interest in the field of evolutionary biology. The advent of whole genome sequencing and comparative genomic methodologies has produced an emerging interest in the study of genomic variation, specifically in regards to the extent, mechanisms, rates and phenotypic effects of mutation. Due in part to their relatively small genome size, well described biodiversity, and social significance, the Fungi have proven to be an ideal model system to conduct comparative genomic investigations of Eukaryotic genomic variation. Accordingly, this dissertation leverages the wealth of Fungal genome data to investigate the evolution of whole genomes across an array of phylogenetic distances. In particular, this work evaluates intron gain and loss, gene family expansion and contraction, gene gain and loss, simple sequence repeat copy number variation, the rapid evolution of proteins and the role of natural selection in shaping variation. Additionally, given its focus on pathogenic Fungi, this work identifies variation between genomes that may contribute to virulence.;In the first chapter, five relatively closely related genomes from the yeast Cryptococcus are compared in an evaluation of gene structure evolution. Included among the observations is a predominance of intron loss over gain, a relatively slow Cryptococcus intron loss rate, and a group of genes that preferentially lose introns. Based the observed patterns of intron loss and gain, population resequencing, and population genetic analysis, mechanisms of intron gain and loss are proposed.;The second chapter evaluates hypotheses about the life history and evolution of the mammalian pathogen Coccidioides via a hierarchical comparative genomics investigation. Comparing the genomes of several Onygenales, including C. immitis and C. posadasii, a close, non-pathogenic relative, Uncinocarpus reesii, and a more diverged pathogenic fungus, Histoplasma capsulatum, to those of 13 more distantly related Ascomycetes, revealed a variety of genomic changes involved in the adaptation of Coccidioides. In particular, this analysis identified increases and decreases in gene family size associated with a host/substrate shift from plants to animals in the Onygenales as well as changes in Coccidioides that may underlie its infectious phenotype. Overall, the results suggest that Coccidioides species are not soil saprophytes, but that they have evolved to remain associated with their dead animal hosts in soil, and that Coccidioides metabolism genes, membrane related proteins and putatively antigenic compounds have evolved in response to interaction with an animal host.;The third chapter considers both the diversity of simple sequence repeats (SSRs) across 21 Fungal lineages as well as the extent of SSR copy number polymorphism within Coccidioides. The results suggest that SSR density evolves rapidly across fungal lineages and correlates with genome size. In addition, the analysis reveals that most SSRs are fixed in Coccidioides, though those that are polymorphic are significantly associated with genes coding for proteins that are secreted or that function at the cell surface. Taken together, the studies reported herein serve to elucidate the mechanisms, rates and effects of genomic variation in the Fungi. |
