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The evolution of host mitochondrial association and its impact on Toxoplasma gondii infection

English, Elizabeth D (2017) The evolution of host mitochondrial association and its impact on Toxoplasma gondii infection. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

The association of intracellular pathogens with host mitochondria has been observed across taxa, from bacterial pathogens, such as Legionella pneumophila and Chlamydia trachomati, to the eukaryotic pathogen Toxoplasma gondii. However the functional impact of host mitochondrial association (HMA) remains difficult to assess in most of these species because in many cases the genes responsible for this phenomenon have not yet been identified. The recent discovery of the T. gondii gene responsible for HMA, Mitochondrial Association Factor 1 (MAF1) has provided us with the tools to begin to understand the evolution and impact of HMA. Here we use multi-species sequence analysis to determine that the MAF1 locus is tandemly duplicated and diversified in both T. gondii and its nearest extant relative Hammondia hammondi, but not another close relative Neospora caninum. Using cross-species complementation we find that T. gondii and H. hammondi harbor copies of MAF1 able to mediate HMA, while N. caninum does not. We have begun mutational analysis using naturally occurring HMA+ and HMA- paralogs of MAF1 in order to determine the portions of MAF1 protein necessary for HMA. Additionally, we have identified the first in vivo phenotypes associated with HMA using multiple mouse models, for both acute and chronic infection. Taken together these data indicate that HMA likely evolved via neofunctionalization of a duplicated ancestral MAF1 gene, and that the neofunctionalized, HMA competent copy of MAF1 provides a selective advantage.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
English, Elizabeth Dede8@pitt.eduede8
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBoyle, Jonboylej@pitt.edu
Committee MemberPipas, Jamespipas@pitt.edu
Committee MemberLawrence, Jeffreyjlawrenc@pitt.edu
Committee MemberRebeiz, Markrebeiz@pitt.edu
Committee MemberCoyne, Carolyncoynec2@pitt.edu
Date: 25 June 2017
Date Type: Publication
Defense Date: 11 January 2017
Approval Date: 25 June 2017
Submission Date: 4 January 2017
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 182
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Toxoplasma gondii, Neospora caninum, Hammondia hammondi, host mitochondrial interaction, neofunctionalization, host-pathogen interactions, host-parasite interactions
Date Deposited: 25 Jun 2017 17:34
Last Modified: 25 Jun 2017 17:34
URI: http://d-scholarship.pitt.edu/id/eprint/30554

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