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Title page for ETD etd-07072016-120006


Type of Document Dissertation
Author LePage, Daniel Paul
Author's Email Address danielplepage@gmail.com
URN etd-07072016-120006
Title The Molecular Basis of Wolbachia-induced Cytoplasmic Incompatibility
Degree PhD
Department Biological Sciences
Advisory Committee
Advisor Name Title
Katherine Friedman Committee Chair
Andrea Page-McCaw Committee Member
Brandt Eichman Committee Member
Julian Hillyer Committee Member
Seth Bordenstein Committee Member
Keywords
  • Wolbachia pipientis
  • cytoplasmic incompatibility
  • Drosophila melanogaster
Date of Defense 2016-06-10
Availability unrestricted
Abstract
Wolbachia pipientis arguably constitute the largest pandemic of the animal kingdom. Estimated to infect 40% of all arthropod species, these obligate intracellular bacteria are masterful controllers of host reproduction and fitness. The most common of these reproductive manipulations is known as cytoplasmic incompatibility (CI). CI manifests as a selective embryonic lethality in crosses between infected males and uninfected females. Infected females, however, are able to rescue these developmental defects in their offspring and thus gain a large fitness advantage that rapidly spreads the maternally-inherited Wolbachia infection. CI has been implicated in several speciation events and is currently being used as a powerful gene drive mechanism to control disease vector populations. Despite decades of research, however, the underlying mechanisms and genetics of CI remain largely unknown.

This study found two Wolbachia genes, tentatively named CI factor A (cifA) and CI factor B (cifB), which are able to induce CI. These genes are derived from the native Wolbachia infection of Drosophila melanogaster, wMel, and when expressed together in uninfected males cause cytological defects and embryonic lethality in crosses to uninfected females. Importantly, these defects are fully rescued by wMel-infected females, similar to wild-type CI. Annotated protein domains suggest that cifB and its homologs may alter host functions by acting as a deubiquitinase or nuclease. Further, cifA and cifB are found in the same operon in every strain of CI-inducing Wolbachia tested. This suggests that, even though cifA has no annotated function in many Wolbachia strains (and possible cytochrome function in at least one), these candidate genes likely interact with each other.

This work also examined the role of various eukaryotic pathways in an effort to identify what host factors may be required for CI. It was found that host DNA methylation machinery was not required, despite being manipulated by Wolbachia for its own benefit, and that expression of the Drosophila DNA methyltransferase Dnmt2 reduces Wolbachia titers. Finally, the D. melanogaster gene JhI-26 was confirmed to be required for complete induction of CI. Future work will determine whether cifA and cifB function through manipulation of JhI-26 or some yet unknown mechanism.

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