Rapid Hox Gene Evolution and the Arthropod Body Plan

Leslie Pick，Proposal 0641717，“Rapid Hox gene evolution and the arthropod body plan“Hox基因决定了所有动物的基本身体计划，并首次在果蝇（Drosophila melanogaster）中发现。 这些基因的突变会导致“同源异型转化”，即身体的一部分被另一部分取代。 例如，触角突变导致触角被完全形成的腿所取代。 当Hox基因被克隆和测序时，人们发现在整个动物王国中都有相同的基因组。 更令人惊讶的是，当小鼠或人类Hox基因在果蝇中表达时，这些基因的行为与果蝇相似。 因此，Hox基因的功能以及它们的序列在动物界中是保守的。 这就产生了一个难题：如果Hox基因决定了不同动物的基本身体结构，但在进化过程中其功能没有改变，那么为什么不同的动物会有不同的基本身体结构呢？是什么让哺乳动物的身体计划不同于苍蝇？ Pick实验室使用遗传学、生物化学和分子方法来解决这个问题。 他们已经确定了一个Hox基因- fushi tarazu（ftz）-其功能在进化过程中发生了巨大的变化。 这个项目的目标是确定ftz在进化过程中的哪些点“切换”了它的功能。 长期目标是研究Hox基因在进化过程中的功能变化如何改变动物的身体结构。 这些研究将对我们理解基因如何调节动物发育的基本过程以及这些基因的进化变化如何导致身体结构的多样化产生广泛的影响。 与此同时，该项目将培训实验室科学的研究生和本科生，并将产生一套分子试剂，与更大的科学界共享。

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.