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Title: Identification, sequencing and characterisation of α-2 adrenergic receptors in the pufferfish (Fugu rubripes)
Author: Hunter, C. I.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2002
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Adrenergic receptors are major pharmaceutical targets, resulting in high investment in their isolation and characterisation. In humans there have been three AR subfamilies identified, alpha-1 (a1), alpha-2 (a2) and beta (b). This report outlines the identification, cloning and subsequent characterisation of a2 AR genes in the Japanese pufferfish, Fugu rubripes. Eight genes, identified in Fugu have been completely sequenced including approximately 1kb of non-coding sequence both upstream and downstream of the coding regions. The sequences have been named by homology, and attempts were made to corroborate these designations by pharmacological studies of the transiently expressed proteins. To date there have been three different a2 AR genes found in man, mouse and other mammals but only two isolated examples in non-mammalian vertebrates. For this reason, regions of a2 AR genes have been isolated from a large number of non-mammalian vertebrates so that the evolution of this gene family may be examined. Fragments of 57 different a2 ARs from all major vertebrate Classes have been sequenced and the data combined with 17 previously sequenced genes to generate phylogenetic profiles and re-construct the evolutionary history of this family in vertebrates. These data have been used to predict whether any more receptors are likely to be present in mammals, and to define approximately where in the vertebrate lineage a gene loss has occurred, resulting in the absence of a fourth gene in mammals. In a more general context, the data has been used to accurately define additional gene duplication(s) specific to the teleost lineage which has led to the presence of up to eight family members in euteleost fish, including Fugu. Additionally the upstream non-coding regions were scrutinised for evidence for conserved regulatory sequences, with no obvious candidate sequences being found. The putative protein sequences were also analysed by sequence similarity for conserved residues that might indicate functional significance.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available