Thesis
Genetic diversity of major surface protein 2 archive is not tightly linked to immune escape
Washington State University
Master of Science (MS), Washington State University
2013
Handle:
https://hdl.handle.net/2376/102645
Abstract
A. marginale is tick-borne pathogen in the Order Rickettsiales that establishes lifelong persistent infection in ruminants. Persistence is achieved by variation of surface proteins to evade the immune response of the host. Variation of major surface protein 2 is achieved by recombination of whole or partial pseudogenes into a single expression site (ES). Once recombined into the ES, the pseudogenes are expressed as functional proteins. Thus, evolution of the pseudogene repertoire is thought to arise under strong selective pressure, in order to diversify alleles and maximize opportunities for immune escape while retaining those alleles that provide a fitness advantage. Analysis of the msp2 repertoire from seven strains of A. marginale shows eight conserved loci that harbor pseudogenes, and that there are identical pseudogene sequences within strains (ie duplicated sequences) as well as between strains (conserved sequences). Comparing across strains reveals that some of the pseudogenes in the duplicated position have segmental changes, suggesting a scenario for evolution of the msp2 pseudogene repertoire: duplication of a pseudogene followed by the accumulation of sequence diversity. We hypothesize that the variant in the "duplicated" position would encode immune escape variants, and thus result in a mechanism for expanding the repertoire of beneficial alleles. We tested this hypothesis by expressing a series of naturally occurring variants from one locus and testing whether these variants provided immune escape from antibodies generated during the course of infection, and we have rejected the hypothesis that variants in the duplicated locus are immune escape variant.
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Details
- Title
- Genetic diversity of major surface protein 2 archive is not tightly linked to immune escape
- Creators
- Pei-Shin Ku
- Contributors
- Kelly A. Brayton (Degree Supervisor)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University; [Pullman, Washington] :
- Identifiers
- 99900525388701842
- Language
- English
- Resource Type
- Thesis