317 CARL Building
Box 3546 DUMC
Durham, N.C. 27710
I received my doctoral training in the laboratory of Dr. Harmit S. Malik at the Fred Hutchinson Cancer Research Center and my PhD in Genome Sciences from the University of Washington. Drawn to the Malik Lab’s interest in genetic conflict and unique strategies using evolutionary tools to answer basic biology questions, I studied how selfish centromeres and protein-protein interactions shape kinetochore proteins. Following my training in the Malik Lab, I joined the Heitman Lab as a Molecular Mycology and Pathogenesis fellow, studying novel sexual cycles in pathogenic fungi.
Sexual reproduction is a defining characteristic of eukaryotic life. The evolutionary advantages of sexual reproduction have long been recognized, principally, purging the genome of deleterious mutations, and the generation of diversity of novel genotypes. In addition to the advantages of sexual reproduction, there are significant costs, namely, the cost of finding a partner and the reduction of the parental genome being transmitted to a progeny. Until quite recently it was thought that most pathogenic fungi were asexual. However, recent research has led to an understanding that most, if not all, pathogenic fungi maintain the ability to engage in sexual reproduction. However, many pathogenic fungi retain sexual cycles with unusual features, including cryptic, parasexual, or unisexual phases.
Cryptococcus neoformans is a basidiomycetous fungus responsible for the majority of opportunistic fungal infections in HIV/AIDS patients. More than one million cryptococcal infections occur annually, causing more than 600,000 deaths. The C. neoformans lifecycle is dominated by growth as a haploid budding yeast with a and α mating type cells. Despite the presence and apparently equal viability of both mating types, α isolates predominate (>95% to 99%) in most natural occurring populations. Under laboratory conditions, C. neoformans is able to undergo both opposite sex mating (a-α) and a novel form of unisexual mating (α-α).
As a Molecular Mycology and Pathogenesis fellow, I am exploring the evolutionary impacts of the unisexual cycle on the fungal development and virulance. Novel sexual cycles may have arisen to provide unique benefits to fungi. Opposite sex mating has the capacity to promote the widest genetic exchange via outcrossing. Unisexual reproduction promotes a more limited genetic exchange and diversity while allowing inbreeding and even selfing to retain beneficial mutations and adaptations. The capacity to engage in both forms of sexual reproduction may be a bet hedging approach that enables microbes to more quickly adapt to specialized environments, first by generating genetic diversity through sexual mating and allowing the fittest phenotypes to retain beneficial adaptations while purging deleterious mutations through unisexual reproduction. Unisexual reproduction can also provide the benefits of the diploid lifecycle, namely the ability to explore adaptive paths not available to haploids, at a lower energetic cost and with less genetic dilution than opposite sex mating. However, the unisexual cycle may have no direct advantage, but instead be a consequence of the grossly unbalanced frequency of the mating types in C. neoformans. The low frequency of a mating type partners dramatically increases the investment required for an α haploid to complete an a-α sexual mating cycle. Therefore, unisexual mating could also act as practice, maintaining the selective pressure to retain the genetic abilty to complete a sexual cycle.
I am currently supported by the Molecular Mycology and Pathogenesis Training Program (T32-AI52080) from the NIH while I investigate these hypotheses, as well as other potential evolutionary consequences of unisexual cycles.