Amelogenin Protein Evolution and Functional Heterochrony

本研究涉及牙釉质和牙釉质蛋白的进化。淀粉原蛋白是牙釉质的主要蛋白质，直接影响牙釉质羟基磷灰石矿物晶体的生长和习性。然而，淀粉原蛋白也存在于有机体中，比如有牙齿但没有牙釉质的海胆和没有牙齿的蟾蜍。进化生物学的一个原理是，相对较小的基因改变可以对形态发生和发育产生深远的影响。本项目将测试淀粉原蛋白基因的进化是否是牙釉质进化的诱因。本项目重点研究淀粉原蛋白c结构域的功能意义。c结构域是中心疏水淀粉原核心的一部分，富含脯氨酸和谷氨酰胺串联重复序列，在海胆、鲨鱼、鱼、蜥蜴、青蛙和老鼠等多种生物中，它们的大小、结构和组成都发生了显著变化。随着牙釉质的进化，牙釉质晶体从短的随机定向模式发展到长而平行的棱镜。为了了解淀粉原蛋白分子的特定结构域如何影响脊椎动物进化过程中牙釉质生物矿化的改变，我们将研究淀粉原蛋白分子在脊椎动物谱系中的命运和功能。有待验证的假设是，釉质晶体从短而随机取向的模式进化到长而平行取向的棱镜，是否与日益复杂的淀粉原蛋白c结构域的进化直接相关，这些结构域促进了复杂的超分子淀粉原亚单位室的组织。目的：1)将釉质/类釉质晶体尺寸与淀粉原蛋白的时空定位和蛋白质结构域结构联系起来；2)在淀粉原蛋白功能的背景下，追踪淀粉原蛋白在脊椎动物谱系中从前淀粉原到远端淀粉原的进化过程；3)比较前淀粉原和远端淀粉原对釉质基质构象、晶体生长和习性的影响。本研究将揭示脊椎动物牙釉质形成的新机制，并将进一步了解复杂结构基因的进化以及生物矿化机制。对生物矿化过程的洞察在纳米技术中有潜在的应用，特别是在新材料的制造、组装和设计方面。

This research is concerned with the evolution of tooth enamel and enamel proteins. Amelogenin is the major protein of tooth enamel and directly affects the growth and habit of enamel hydroxyapatite mineral crystals. However amelogenin also occurs in organisms such as sea urchins that have teeth but lack enamel and toads which lack teeth. One principal in evolutionary biology is that relatively small genetic alterations can have profound affects on morphogenesis and development. This project will test whether the evolution of the amelogenin gene is the causal agent for the evolution of tooth enamel. This project focuses on the functional significance of the amelogenin C-domain. The C-domain is part of the central hydrophobic amelogenin core rich in proline and glutamine tandem repeats that change significantly in size, structure, and composition among organisms as diverse as sea urchins, sharks, fish, lizards, frogs, and mice. As tooth enamel has evolved, enamel crystals have proceeded from short randomly oriented patterns to long and parallel prisms. In order to gain an understanding how specific structural domains of the amelogenin molecule might affect alterations in enamel biomineralization during vertebrate evolution, the fate and function of the amelogenin molecule in vertebrate lineages will be studied. The hypothesis to be tested is whether the evolution of enamel crystals from short and randomly oriented patterns to long and parallel-oriented prisms is directly linked to the evolution of increasingly sophisticated amelogenin C-domains facilitating the organization of complex supra-molecular amelogenin subunit-compartments. Aims are 1) to correlate enamel/enameloid crystal dimensions to amelogenin temporo-spatial localization and protein domain configuration, 2) to trace the evolution of amelogenins from pro-amelogenin to teleo-amelogenin in vertebrate lineages in the context of amelogenin protein function, 3) to compare the effects of pro-amelogenin with the effects of teleo-amelogenin on enamel matrix conformation and crystal growth and habit.This research will shed new light on mechanisms involved in vertebrate enamel formation and will generate further understanding of the evolution of complex structural genes as well as mechanisms of biomineralization. Insight into biomineralization processes has potential applications in nanotechnology particularly with regard to the fabrication, assembly, and design of new materials .