Date of Award

Fall 12-2021

Level of Access Assigned by Author

Open-Access Thesis

Degree Name

Master of Science (MS)

Department

Ecology and Environmental Sciences

Advisor

Pauline Kamath

Second Committee Member

Kristina Cammen

Third Committee Member

Benjamin King

Abstract

Pathogens are significant selective forces on natural populations, and therefore genes and gene regulators involved with combatting infections experience some of the strongest selection pressures in the vertebrate genome. Studies in humans have used high-throughput next generation sequencing to identify genes associated with infectious diseases, however, these studies have been limited in wildlife systems despite their potential to improve public health, agricultural production, and wildlife conservation. Anthrax is a globally distributed disease caused by the virulent bacterial pathogen Bacillus anthracis, which has significant effects on morbidity and mortality in humans, livestock, and wildlife populations. In this study, we utilize whole genome sequencing to identify genetic loci associated with resistance to naturally occurring B. anthracis infections in a plains zebra (Equus quagga) population of Etosha National Park (ENP), Namibia. In ENP, anthrax is endemic and outbreaks occur annually in herbivorous ungulates, with plains zebra contributing to the largest proportion of the observed anthrax mortalities. We sequenced the genomes of 31 individuals who were exposed to anthrax but survived (controls) and 27 individuals that died from B. anthracis infection (cases) during three outbreak years (2008-2010). We used three tests to find genomic variants that were differentiated between survivors and non-survivors, annotated the variants to genes, and collected biological significance data to describe their putative roles in surviving anthrax outbreaks. We also developed a novel weighting scheme for assessing the relative importance of functional gene pathways associated with the identified gene set. The tests identified 8,522 variants that differed between the groups, of which 1,600 were in gene regions. As expected, we found several genes (e.g., ANTXR2, KLRK1, MAP2Ks) associated with survival that were previously described as involved with initial anthrax toxin entry, disruption, and immune response. More surprisingly, we also found many genes that are more likely to either be associated with behavior or late-stage systemic resistance to anthrax (e.g., GRIK1, JPH3, CAMK2D), rather than to early or immunological resistance. We suggest that survival outcome of endemic anthrax outbreaks in ENP stems from a wide array of phenotypes beyond an individual’s immunological capacity. These GWAS results will be of interest to members of the medical and veterinary fields as we confirmed previously reported genes of anthrax pathogenesis and identified new genes that could have implications for the future development of anthrax treatments and vaccines for both livestock and humans.

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