东亚人群两种适应性表型的遗传进化研究
文献类型：学位论文
| 作者 | 彭忆 |
| 学位类别 | 博士 |
| 答辩日期 | 2012-05 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 宿兵 |
| 关键词 | 东亚人群 适应性进化 ADH1BArg47His多态位点 EPAS1基因 高原低氧适应 |
| 其他题名 | The genetic and evolutionary study for the two adaptative phenotype in East Asian |
| 学位专业 | 遗传学 |
| 中文摘要 | 从达尔文时代以来，人类学家和进化生物学家的一个关注重点是人类群体的多样性是如何进化而来的。自然选择进化理论认为：环境改变是进化的主要动力。现代人自从非洲起源以来，在最近10万年的时间中已经分布到了全球几乎所有地理区域中。在这一过程中，自然环境和社会习俗的改变都可能对人类遗传变异产生影响。在本研究中，我们对东亚人群中的两种重要的适应性性状，酒精耐受和高原适应，进行了人类群体遗传学和进化生物学方面的分析。 首先，我们从遗传上证明了Ⅰ型乙醇脱氢酶ADH1BArg47His多态位点是随着东亚地区的水稻驯化起源和扩张而在东亚人群中扩散开来。从1万年前人类社会进入农业时代以来，饮食等方面的改变对新石器时代的人类遗传变异就产生了持续的影响。而在南部中国及其邻近区域群体中高频的Ⅰ型乙醇脱氢酶Arg47His多态位点已经被证明存在明显的达尔文正选择作用。在我们的研究中，我们对包括汉族、藏族和东亚其他民族在内的38个群体的2,275个个体进行了群体遗传学研究。我们发现在这些群体中的ADH1B*47His突变频率表现出明显的自东向西的梯度变化，在东部地区的各个群体中频率较高而在西部的藏族群体中频率很低。对ADH1B*47His突变起源时间所做的年代估计则发现该突变在东亚地区大规模扩散的时间发生在7,000-10,000年前。ADH1B*47His突变频率的地理分布模式与东亚地区的古水稻遗址的时空分布高度一致。这些证据说明在东亚地区，尤其是中国东南部新石器时代的农业起源和扩张的时间与ADH1B*47His突变在相应的人群中开始扩散的时间是高度重合的。 在第二部分的研究中，我们利用Affymetrix Genome-wide Human SNP Array 6.0芯片对来自不同地域的50个藏族个体进行了全基因组扫描。我们通过扫描鉴定出了两个在藏族高原适应中可能发挥主要作用的低氧代谢通路相关基因，EPAS1基因和EGLN1基因。 人类为了成功应对极端恶劣的高原环境，例如寒冷、强紫外线辐射和高原低氧等，会在行为和生理上做出相应的适应性改变。在这些环境压力中，高原低氧是唯一一种无法用传统技术手段克服的环境压力。由于长期生活在海拔3,000m以上的高原，藏族人群为我们提供了一个极好的研究人类高海拔适应的例子。但直到最近，藏族人群适应高原低氧极端环境的遗传机制仍然没有被发现。我们对藏族人群的序列变异进行了全基因组扫描，并且通过与其他研究比较分析发现了两个低氧相关基因，EPAS1基因和EGLN1基因中存在明显的选择性清洗（selective sweep）信号。在这两个基因及其附近的基因组区域中，藏族人群携带了大量的与其他平原人群（例如汉族和日本人群）不同的遗传变异，同时我们还在藏族人群的EPAS1基因中发现了一个藏族特异的单倍型，这个单倍型携带了数量众多且高频连锁的遗传变异。对不同地区的7个藏族人群共1,334个个体所做的进一步群体遗传学分析发现在整个喜马拉雅地区的群体中都存在这种选择性清洗的信号。在EPAS1基因和EGLN1基因中所出现的自然选择信号表明，藏族人群为了适应高原低氧的环境在这两个基因中出现了高频的适应性功能突变。 |
| 英文摘要 | Sincethe age of Darwin, anthropologists and evolutionary biologists have been wonderinghow the diversity of human population has evolved. The theory of natural selection indicates that the environmental change is the driving force of evolution. Modern humans have occupied almost all possible environments globally since exiting Africa about 100,000 years ago. Thechanges of social and natural environments can have a great impact on the genetic makeup of human populations. The alcohol tolerance and high altitude adaptation are the two well-known adaptive phenotypes among East Asians. In this study, we conducted human population genetics and evolutionary analysis in understanding the genetic basis of these phenotypes. First, we presented genetic evidence of selection on the class I alcohol dehydrogenase sequence polymorphism (ADH1BArg47His) caused by the emergence and expansion of rice domestication in East Asia. The diet shift in agriculture societies about 10,000 years ago may have a great impact on the genetic makeup of Neolithic human populations. The regionally restricted enrichment of ADH1BArg47His in southern China and the adjacent areas suggests Darwinian positive selection on this genetic locus during Neolithic time though the driving force is yet to be disclosed. In our study, we studied a total of 38 populations (2,275 individuals) including Han Chinese, Tibetan and other ethnic populations across China. The geographic distribution of the ADH1B*47His allele in these populations showed a clear east-to-west cline, and it is dominant in southeastern populations but rare in Tibetan populations. The molecular dating indicated that the emergence of the ADH1B*47His allele occurred about 10,000~7,000 years ago. The geographic distribution of the ADH1B*47His allele in East Asia is consistent with the unearthed culture relic sites of rice domestication in China. And we found that the estimated origin age of ADH1B*47His allele in those populations coincided with the time of Neolithic agriculture origin and expansion in southern China. Second, we first conducted a genome-wide scan in 50 Tibetan individuals from different geographic populations using Affymetrix Genome-wide Human SNP Array 6.0 and identified two major candidate genes, EPAS1 and EGLN1, the two key regulators for hypoxia are likely the causal genes for high altitude adaptation in Tibetans. Both behavioral and biological adaptations have contributed to human success in surviving the rigors of climatic extremes, including cold, strong ultraviolet radiation, and high altitude. Among these environmental stresses, high-altitude hypoxia is the only condition in which traditional technology is incapable of mediating its effects. Inhabiting at 4,000-m high plateau, the Tibetan population provides a widely studied example of high-altitude adaptation. Yet, the genetic mechanisms underpinning long-term survival in this environmental extreme remain unknown. We performed an analysis of genome-wide sequence variations in Tibetans. In combination with the reported data, we identified strong signals of selective sweep in two hypoxia-related genes, EPAS1 and EGLN1. For these two genes, Tibetans show unusually high divergence from the non-Tibetan lowlanders (Han Chinese and Japanese) and possess high frequencies of many linked sequence variations as reflected by the Tibetan-specific haplotypes. Further analysis in seven Tibetan populations (1,334 individuals) indicates the prevalence of selective sweep across the Himalayan region. The observed indicators of natural selection on EPAS1 and EGLN1 suggest that during the long-term occupation of high-altitude areas, the functional sequence variations for acquiring biological adaptation to high-altitude hypoxia have been enriched in Tibetan populations. |
| 语种 | 中文 |
| 公开日期 | 2013-04-22 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7363]  |
| 专题 | 昆明动物研究所_比较基因组学 |
| 推荐引用方式 GB/T 7714 | 彭忆. 东亚人群两种适应性表型的遗传进化研究[D]. 北京. 中国科学院研究生院. 2012. |
入库方式： OAI收割
来源：昆明动物研究所
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