Rapid Hox Gene Evolution and the Arthropod Body Plan

Leslie Pick，提案0641717，“快速Hox基因进化和节肢动物身体计划”Hox基因决定了所有动物的基本身体计划，并首次在果蝇--黑腹果蝇中被发现。这些基因的突变会导致“同源异型转化”，即身体的一个部位被另一个身体部位取代。例如，天线的突变会导致天线被完全成形的腿取代。当对HOX基因进行克隆和测序时，人们发现整个动物界都有相同的一组基因。更令人惊讶的是，当老鼠或人类的HOX基因在果蝇中表达时，这些基因的行为与果蝇的同类基因相似。因此，HOX基因的功能以及它们的序列在整个动物界都是保守的。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计划，但在进化过程中功能没有变化，为什么不同的动物有不同的基本身体计划？哺乳动物的身体规划与苍蝇的身体规划有什么不同？Pick实验室使用了遗传学、生物化学和分子方法来解决这个问题。他们已经确定了一种HOX基因--福氏Tarazu(FTZ)--其功能在进化过程中发生了戏剧性的变化。这个项目的目标是确定自贸区在进化过程中的哪些点“切换”了它的功能。更长期的目标是研究HOX基因在进化过程中功能的变化如何改变动物的身体计划。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多样化产生广泛影响。与此同时，该项目将培训研究生和本科生在实验室科学方面，并将产生一套分子试剂，将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.