东亚人群牙齿形态特征的基因组变异及其进化机制研究

Teeth, as one of the easiest retained archaeological material, have great significance in human morphology evolution and human evolutionary history. However, the dental morphology provided controversial supports on the two hypothesis of the origin of East Asians (Out of African hypothesis and multiple local origin of human race). Heritability studies discovered that the heritability of dental morphology is up to 60% in human. However, the genetic research based on genes still remained scarce. In previous study, we discovered that the nonsynonymous mutation EDARV370A, which influenced incisors shoveling in several East Asian populations, originated about 30,000 years ago in East Asia. This indicates that the incisors shoveling in Modern East Asians most probably appeared after the late Pleistocene. In this project, we plan to employ the whole-genome chip data on Taizhou Cohort to locate the genes of eleven dental morphology phenotypes which provided controversial supports on the two hypothesis of the origin of East Asians. Further, we would sequence candidate genes of above dental morphologies to ascertain the potential mutations causing corresponding phenotypes. The age of the potential casual mutations would be estimated to test the hypothesis of the origin of East Asians. The accomplishment of this project would lay foundation for the genetics and evolution of East Asian dental morphology and reveal the origin of East Asians.

牙齿是考古最容易保留下来的材料之一，对阐明人类形态特征演变以及人类进化历史具有重要意义。但牙齿的形态在解释东亚人类起源两种学说（现代人起源替代学说和多地区起源学说）争议极大。人类牙齿形态特征的遗传度高达60%，但目前基因层面上的研究还屈指可数。项目组前期研究发现东亚群体中铲形门齿等特征受到遗传变异EDARV370A的影响，而通过时间估算该变异大约起源于3万年前，由此推断现代东亚人群的铲形门齿可能是更新世晚期以后进化的产物。在此基础上，本项目拟将研究扩大到基因组层面，利用前期积累的1000例泰州汉族队列样本的全基因组扫描数据，对东亚人起源两种学说存在争议的11项牙齿形态进行基因定位。后续拟对定位基因进行测序，确定可能影响形态的突变并估算突变产生的时间，来确定相应牙齿形态所支持的东亚人起源学说理论。项目的完成将为揭示现代东亚人牙齿形态特征的遗传进化机制打下重要的基础，对阐明东亚人起源意义重大。