Graduate Thesis Or Dissertation
 

What Makes a Fish Resistant? Comparative Genomics and Transcriptomics of Oncorhynchus mykiss with Differential Resistance to the Parasite Ceratonova shasta

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  • The myxozoan Ceratonova shasta is an intestinal parasite of salmon and trout that causes ceratomyxosis, a disease characterized by severe inflammation of the intestine that can lead to hemorrhaging, necrosis, and death of the fish host. The parasite is endemic to the Pacific Northwest of the United States and Canada, where it has been linked to the decline of wild fish stocks. The parasite exerts a strong selective force on its fish host, and fish populations from C. shasta endemic watersheds become genetically fixed for resistance to ceratomyxosis. This contrasts with fish from watersheds where the parasite is not established, who are highly susceptible the disease, with a single spore capable of causing a lethal infection. Management of the disease relies on selective stocking of resistant fish, however, even these fish can succumb to the infection. Understanding the genetic and immunological basis of resistance to this disease would provide the framework for the development of therapeutics and identification of genetic markers that could be used in selective breeding. In this project, we employed a comparative transcriptomics and genomics approach to understand how resistant and susceptible strains of Oncorhynchus mykiss (rainbow trout/steelhead) respond to C. shasta infection and identify the genomic loci conferring resistance. We found that infection by C. shasta has an immunosuppressive effect in both resistant and susceptible fish, with IFNγ and interferon stimulated genes being downregulated in the gills, which is the portal of entry for the parasite. Once the parasite reaches the intestine, resistant fish quickly respond with an IFNγ driven TH1 response, and upregulation of MHC class I genes and genes involved in antigen processing and presentation. This response suggests that C. shasta has an intracellular phase during its migration to the intestine, which may represent a form of immune evasion that causes the host to initiate a cytotoxic T-cell response that is ineffective against the extracellular stages in the intestine. Susceptible fish, on the other hand, had no detectable immune response to the parasite reaching the intestine, highlighting the importance of parasite recognition in the different infection outcomes of these fish. In addition to a more rapid immune response, resistant fish have a tissue level response that limits the spread of the parasite within the intestine and allows them to regenerate their intestinal lining. Additionally, we have identified a region on chromosome Omy9 that significantly affects the odds of surviving C. shasta infection, and a region on Omy11 with a lesser contribution to survival. Taken together, this research represents a major step forward in our understanding of both the genetic and immunological basis of resistance to this important parasite.
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  • This work was funded by the Bureau of Reclamation, U.S. Department of Interior through Interagency Agreement # R19PG00027. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscripts.
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file details DamienBarrettE2020.pdf 2020-09-21 公开 下载