DISSERTATION RESEARCH: EVOLUTION OF ESTROGEN RECEPTOR FUNCTION IN THE MOLLUSK, OCTOPUS VULGARIS
Joseph W. Thornton June Keay
University of Oregon
Virtually all the functions of living cells are regulated by specific interactions between molecules, such as those between hormones and receptors, enzymes and substrates, and transcription factors and DNA binding sites. Very little is known, however, about how these molecular interactions evolved. This project focuses on the evolution of interactions between estrogens - a group of hormones crucial for development and reproduction in vertebrates -- and the estrogen receptor (ER) protein. In vertebrates, binding of estrogens enables the ER to increase expression of hormone-responsive genes. Preliminary data indicate the ER in mollusks has lost this interaction with estradiol, and that it always activates transcription, whether or not the hormone is present. This variation presents the opportunity to study the evolution of ER's functional interaction with hormones. Specifically, this project will investigate the evolution of ER function in the common octopus (Octopus vulgaris), a mollusk in which estrogen appears to have a reproductive role. The molecular functions of the octopus ER will be determined, the ER sequence of the ancient common ancestor of vertebrates and mollusks will be reconstructed, and hypotheses about the evolution of variant ER functions will be tested by synthesizing the ancestral receptor and using site-directed mutagenesis. This research will provide important comparative data for understanding ER function and evolution in humans and other animals. It will also provide important information on the potential scope of environmental endocrine disruption, a major issue in environmental and wildlife health. This project will contribute to the next generation of scientists by supporting the research training of a talented female scientist in cutting-edge techniques of molecular evolution, gene function, and endocrinology.