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dc.contributor.advisorBernstein, Harrisen_US
dc.contributor.authorChen, Hao
dc.creatorChen, Haoen_US
dc.date.accessioned2011-12-06T13:53:08Z
dc.date.available2011-12-06T13:53:08Z
dc.date.issued2010en_US
dc.identifier.urihttp://hdl.handle.net/10150/195455
dc.description.abstractModels proposed for the molecular evolution of the immune system are based on comparative studies of living species. Sharks are critical in this regard since they belong to an ancient clade (chrondrichthyans) that can be traced in the fossil record to the time of the earliest vertebrates. Approximately 450 million years ago, the gnathostomes diverged into two groups, the chondrichthyans (sharks and rays) and the osteichthyans (line leading to modern teleosts and tetrapods). It can be concluded that the molecular components of the immune system are ancient and arose prior to this divergence. This follows from studies showing that all the defining elements of the immune system, antibodies, T cell receptors (TCRs), MHC products and recombination activator genes (RAG), are present in chondrichthyes (4, 5). Thus, continued studies of sharks and rays, the most distant living relatives of mammals with a vertebrate type (VDJ-C recombination) immune system, should provide insights into the molecular origins and evolution of the immune system.In this research, 1) I report the sequence of the sandbar shark TCR gamma chain genomic locus and confirm that it has a prototypical translocon arrangement. 2) I also show that in the sandbar shark TCR gamma V regions undergo somatic hypermutation, in addition to DNA recombination and junction addition and deletion, to generate TCR diversity.3) Ireport the sequence of the sandbar shark beta-2 microglobulin (b2m)genomic locus.These findings certainly have functional implications for gamma/delta T cells, b2m and MHCs in sharks, and may have phylogenetic significance for understanding the evolutionary origins of diversity in the immune system.
dc.language.isoENen_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.titleTHE EVOLUTION OF THE ADAPTIVE IMMUNE SYSTEMen_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.identifier.oclc659753699en_US
thesis.degree.grantorUniversity of Arizonaen_US
thesis.degree.leveldoctoralen_US
dc.contributor.committeememberBernstein, Harrisen_US
dc.contributor.committeememberHarris, Daviden_US
dc.contributor.committeememberAblin, Richarden_US
dc.contributor.committeememberSchluter, Samuel F.en_US
dc.contributor.committeememberNikolich-Zugich, Jankoen_US
dc.identifier.proquest10824en_US
thesis.degree.disciplineImmunobiologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.namePh.D.en_US
refterms.dateFOA2018-06-12T09:58:42Z
html.description.abstractModels proposed for the molecular evolution of the immune system are based on comparative studies of living species. Sharks are critical in this regard since they belong to an ancient clade (chrondrichthyans) that can be traced in the fossil record to the time of the earliest vertebrates. Approximately 450 million years ago, the gnathostomes diverged into two groups, the chondrichthyans (sharks and rays) and the osteichthyans (line leading to modern teleosts and tetrapods). It can be concluded that the molecular components of the immune system are ancient and arose prior to this divergence. This follows from studies showing that all the defining elements of the immune system, antibodies, T cell receptors (TCRs), MHC products and recombination activator genes (RAG), are present in chondrichthyes (4, 5). Thus, continued studies of sharks and rays, the most distant living relatives of mammals with a vertebrate type (VDJ-C recombination) immune system, should provide insights into the molecular origins and evolution of the immune system.In this research, 1) I report the sequence of the sandbar shark TCR gamma chain genomic locus and confirm that it has a prototypical translocon arrangement. 2) I also show that in the sandbar shark TCR gamma V regions undergo somatic hypermutation, in addition to DNA recombination and junction addition and deletion, to generate TCR diversity.3) Ireport the sequence of the sandbar shark beta-2 microglobulin (b2m)genomic locus.These findings certainly have functional implications for gamma/delta T cells, b2m and MHCs in sharks, and may have phylogenetic significance for understanding the evolutionary origins of diversity in the immune system.


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