Date of Award
Doctor of Philosophy
Richard Gerhold, Jae Park, Todd Reynolds, Tim Sparer
Toxoplasma gondii is among the most widespread eukaryotic pathogens known. It chronically infects approximately one third of the world’s human population and has been isolated from an extremely diverse array of globally distributed mammals and birds. Understanding the structure of the worldwide T. gondii population enhances our understanding of the factors that have shaped that structure and led to the proliferation of one of the most evolutionarily successful pathogens on Earth. Herein we collate genotypic data from global isolates, demonstrating that T. gondii possesses a unique population structure in which only a small number of genotypes dominate throughout the northern hemisphere, but myriad types coexist in South and Central America with none being notably dominant. On average, South American strains were also found to be more virulent to mice than their northern counterparts. We propose that the clonal population structure in the northern hemisphere is the consequence of the domestic cat-house mouse transmission cycle, which has been greatly enhanced by the spread of human agriculture in the past 11,000 years, and that this transmission cycle plays a significant role in the selection of intermediately virulent T. gondii genotypes. To test this idea, we compiled strain virulence and sequential reinfection data. Simulations based on the composite dataset were used to predict patterns of mouse virulence evolution in T. gondii populations. Our results indicate an advantage relating to the mouse virulence of particular strain types within the domestic cat–house mouse transmission cycle. However, such selective pressure is alleviated in the context of a sylvatic cycle, in which most wild intermediate hosts are resistant to T. gondii infection. This suggests that highly mouse-virulent parasite types have an adaptive advantage during transmission in environments that are rich in wildlife species, such as the tropical rainforests of South America. Mouse virulence was found to be closely associated with particular alleles encoding parasite proteins ROP5 and ROP18, making these markers valuable tools for predicting virulence of future environmental isolates. The results of this study have significant implications concerning the evolution of T. gondii in agrarian and urbanized environments and transmission of T. gondii to humans.
Shwab, Elliot Keats Cullen, "Genetic Diversity, Population Structure, and Evolution of Virulence in Toxoplasma gondii. " PhD diss., University of Tennessee, 2015.