DeSalle 9870055 Genetic changes have produced novel biochemical functions during the course of evolution. This study addresses the way in which these changes have occurred using nuclear receptor proteins. The superfamily of nuclear receptor proteins comprises over 50 related transcription factors that regulate reproduction, development, metamorphosis, and the maintenance of homeostasis in a broad range of animal taxa from jellyfish to humans. The superfamily includes receptors for steroid and thyroid hormones (including estrogen and testosterone), retinoic acids, vitamin D, and insect ecdysteroids, as well as a large number of orphan receptors, the ligands for which receptors are unknown or may not exist. Despite extensive information on nuclear receptor function, the evolutionary history of this group of physiologically important genes is obscure. This research project seeks to elucidate the history with the following specific aims: 1) reconstruction of the phylogenetic relationships among the nuclear receptors using parsimony-based analysis of existing molecular sequence data; 2) generation of molecular sequence information for steroid receptor sequences from several species of lamprey, the most ancient extant vertebrate lineage, in order to specify when specific proteins evolved through duplication and divergence events, and to provide data for a comparative analysis of the evolution of steroid receptor protein sequences; and 3) characterization of the mechanisms and dynamics by which genetic change has produced novel functions among the steroid receptors, by analyzing in a phylogenetic context the correlated evolution of molecular and functional characters, the rate of divergence, and the patterns of genomic organization in this important and well-studied class of proteins.
