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The evolution of the adaptive immune system

Posted on:2011-07-19Degree:Ph.DType:Dissertation
University:The University of ArizonaCandidate:Chen, HaoFull Text:PDF
GTID:1448390002951975Subject:Biology
Abstract/Summary:
Models 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 gammaV regions undergo somatic hypermutation, in addition to DNA recombination and junction addition and deletion, to generate TCR diversity. (3) I report the sequence of the sandbar shark beta-2 microglobulin (beta2m)genomic locus.;These findings certainly have functional implications for gamma/delta T cells, beta2m and MHCs in sharks, and may have phylogenetic significance for understanding the evolutionary origins of diversity in the immune system.
Keywords/Search Tags:Immune system, Evolution, Sharks
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