Leslie Pick, Proposal 0641717, "Rapid Hox gene evolution and the arthropod body plan"
Hox genes determine the basic body plans of all animals and were first discovered in the fruit fly, Drosophila melanogaster. Mutations in these genes cause "homeotic transformations", where one body part is replaced by an alternate body part. For example, the Antennapedia mutation causes the antenna to be replaced by a fully formed leg. When Hox genes were cloned and sequenced, it was found that the same set of genes is throughout the animal kingdom. More surprising was the finding that when mouse or human Hox genes were expressed in fruit flies, the genes behaved like their fly counterparts. Thus, the function of Hox genes as well as their sequence has been conserved across the animal kingdom. This creates a conundrum: if Hox genes determine the basic body plan of different animals, but have not changed in function during evolution, how is it that different animals have different basic body plans? What makes the mammalian body plan different from that of the fly? The Pick laboratory has used genetic, biochemical and molecular approaches to address this question. They have identified one Hox gene - fushi tarazu (ftz) - whose function has changed quite dramatically during evolution. The goals of this project are to determine at which points during evolution ftz "switched" its function. The longer-term goal is to ask how the change in function of a Hox gene during evolution altered the animal body plan. These studies will have broad impacts on our understanding of how genes regulate basic processes of animal development and how evolutionary changes in such genes result in diversification of body structures. At the same time, this project will train both graduate and undergraduate students in laboratory science and will generate a set of molecular reagents that will be shared with the larger scientific community.
