甜味，作为重要的味觉之一，帮助动物寻找到富含高碳水化合物的食物，以保证能量的摄入， 同时还能增强摄食的欲望，是人类以及大多数物种喜爱的味觉。 甜味受体基因发现以前，行为学以及电生理的实验已揭示了物种水平以及物种内的甜味感受存在差异。部分对人而言是甜的物质，在一些物种中没有选择偏好，尤其离人类亲缘关系越远的物种倾向于无法感知人工甜味剂。2001 年，甜味受体的本质被揭开：是由两个G蛋白偶联受体 Tas1R2 和Tas1R3 构成的异源二聚体。甜味受体基因的发现掀起了甜味受体与配体作用机制的研究高潮，但我们对物种间甜味感知差异的机制却没有系统的认识，为了更进一步了解哺乳动物甜味受体的功能和进化，我们选择了具有不同甜味感知能力，并且系统发育关系明确的 7个灵长类物种为研究对象，进行细胞层面的功能实验以及序列上的进化分析。 通过功能实验，发现所选的灵长类中只有人类对所有的甜味剂（包括人工甜味剂和天然甜味剂）都敏感，并且敏感度和反应强度都显著的高于其他物种。黑猩猩和猕猴次之，其他物种差异不显著。嵌合体的功能实验结果显示：Tas1R3亚基的功能在人科动物的共同祖先处增强；Tas1R2亚基的功能在灵长类的进化过程中分歧较大，发生了至少两次的增强，其中最近，也是最确切的一次发生在人类和黑猩猩的共同祖先处；而且甜味受体功能的强弱还深受两个亚基相互作用的影响。同时，灵长类甜味受体的进化分析结果显示灵长类的甜味受体倾向于受到纯化选择。因为物种间，相同亚基极小的序列差异就能导致功能的显著差异，而且受体的功能还受到亚基互作的影响，所以纯化选择的发生能维持基因在功能上的保守性与稳定性。本研究首次系统的对灵长类物种的甜味受体进行功能实验和进化分析的研究，一定程度的揭示了灵长类甜味受体功能的演化，以及甜味受体亚基互作对甜味受体功能的影响。这将为哺乳动物甜味受体的功能和进化研究提供新的视野。; Sweet taste, as one of the most important gustation qualities helps animals to identify carbohydrate-rich food and to ensure the intake of energy, and increase appetite, so that favored by human and almost all mammals. The difference of sweet perception within species had been already found before sweet taste receptor identified. On the whole, the difference of sweet perception is significant. The species relatives far away from human tend to be indifferent to artificial sweet ligands. Such as aspartame and cyclamate, only can be perceived by Old World monkey, apes and human, therefore Glaser et al. concluded that the ability to recognize aspartame as sweet is a recent evolutionary development, occurring in a common ancestor of Old World simians. In order to understand more about the function and evolution of primates sweet taste receptor we choose 7 primates, which have different sweet taste ability as well as clear phylogenetic relationship, to do functional experiments in vitro and sequence evolutionary analysis. The results show that only human sweet taste receptor is most sensitive to all the ligands, include natural and artificial, in whole primates, and the sensitivity, response intensity are also significantly higher than other species; chimpanzee and macaque come second. Another species is not significant. Though chimera functional experiments we find out Tas1R3 subunit gained the function in a common ancestor of Hominids, while Tas1R2 subunit seems though a complex pattern of evolution. It experiences at least two function gain, the most certain one occurring in a common ancestor of human and chimpanzee. In addition, the interaction of this two subunits greatly affect the function of sweet taste receptor. The evolution analysis demonstrates that sweet taste receptor tends to be under purifying selection in primates. Because the tiny sequence variation can cause significant functional difference. Occurring of purifying selection may maintain the stable and conservative function of sweet taste receptor. This is the first time to systematic focus on primates sweet taste receptor using functional experiment and evolution analysis, and demonstrates the evolution pattern of primates sweet taste receptor. It will provide new vision for future study of mammal sweet taste receptor function and evolution.
修改评论