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Title: Pathogen evolution and spread in the face of host genetic diversity
Author: Ekroth, Alice Katarina Elizabeth
ISNI:       0000 0004 9351 3402
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2020
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Despite the strong forces of genetic drift and directional selection, virtually all natural populations are genetically diverse. Declining within-host population diversity is nevertheless a growing problem, with homogenous populations (known as ‘monocultures’) predicted to suffer the most from pathogen (and/or parasite, herein used interchangeably where the same principles apply to both) infection given the increasing likelihood of uniform susceptibility. The literature has shown conclusively that genetically diverse populations stand a better chance of limiting infection by natural pathogens (otherwise known as the monoculture effect) or pathogens for which genetic variation for resistance exists in the host population. However, the impacts of within- and between-host population genetic relatedness in the face of novel pathogens has not been tested. In this thesis, I combined meta-analytic and experimental evolution approaches to explore the impacts of host population genetic diversity on pathogen spread and evolution. Firstly, I gathered data from a wide range of host-pathogen interactions to test the effects of two levels of host within-population diversity (low and high) on parasite success in a formal meta-analysis. Among other findings, this study revealed broad-spectrum support for the observation that low diversity increases the chance of parasite success across systems. Secondly, I used experimental evolution and follow-on genomics analysis to track the evolutionary dynamics of Staphylococcus aureus as a novel infection in an array of natural, susceptible Caenorhabditis elegans isolates. I found that the pathogen evolved similar virulence in closely-related hosts, with infection load evolving along an independent trajectory. I also found that S. aureus performs better (i.e., more virulent and higher infection loads) in a diverse population of distantly-related hosts compared to a population of closely-related hosts. Thirdly, I investigated whether S. aureus maintained its generalist infection ability throughout evolution in the novel C. elegans populations. I discovered that despite evolving in monocultures of particular host isolates, evolved S. aureus was able to infect sympatric and novel hosts equally. Moreover, pathogen performance between these host types was not negatively related to the genetic distance between them. As a whole, this body of work confirms that the host genetic diversity shapes the ecology and evolution of natural and novel pathogens across the tree of life. It additionally extends on knowledge of the monoculture effect to the wider concern of novel infections, and thereby improves our understanding of how host population genetic composition might be used to control the spread and evolution of new emerging infectious diseases.
Supervisor: King, Kayla Sponsor: Natural Environment Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Caenorhabditis elegans ; Staphylococcal infections ; Bacterial diversity ; Meta-analysis ; Host-parasite relationships