HUMAN DNA POLYMORPHISM AND EVOLUTION

这个项目有3个目标。1.DNA多态水平的研究 在世界各地的不同人类群体中，提供了一个基因组--和 世界范围的图景。第一个授权期的主要目的是 在选择的情况下获得核苷酸多样性的可靠估计 通过使用非编码序列实现中立性；这样的估计具有 巨大的参考价值，例如，它可以作为 比较来自世界其他地区的核苷酸多样性水平 基因组。2.解决长期存在的关于原产地和 现代人的进化。流行的观点是，“完整的 取而代之“或”走出非洲“模式，假定非洲起源于 现代人和土著的快速、完全的更替 世界上所有其他地区的人口按非洲种群计算。 相反的观点，“多区域进化”模型，假定 古代地域性人类的渐进、同步转变 通过基因流动和自然选择将种群转变为现代种群。这个 以前的观点暗示，非非洲古人类没有做出任何贡献 或者对目前的人类基因库几乎没有什么影响，而后者认为 预测了世界上至少部分地区的遗传连续性。至 为了实现这两个目标，我们建议将(A)250个序列标记为 300个碱基对或更长的位点(单拷贝序列)和(B)10 不同种群中的非编码区(每个约10kb) 整个世界。3.发展DNA分析的统计方法 多态数据，特别是对于解决上述争议和 用于研究人类进化和总体上的种群结构。我们 应考虑重组、种群细分、 人口增长和自然选择，其中大部分还没有 在目前的方法中考虑。新的方法和现有的一些方法 将使用的方法来分析所获得的数据。新方法 将可在万维网上访问。

This project has 3 goals. 1. To study the levels of DNA polymor-phism in various human populations over the world, providing a genome- and world-wide picture. The major aim of the first grant period is to obtain a reliable estimate of nucleotide diversity under selective neutrality by using noncoding sequences; such an estimate has a tremendous reference value, e.g., it can serve as a standard for comparing the levels of nucleotide diversity from other parts of the genome. 2. To resolve the long-standing controversy over the origin and evolution of modern humans. The prevailing view, the "complete replacement" or "Out of Africa" model, postulates an African origin for modern humans and a rapid, complete replacement of indigenous populations in all other regions of the world by the African stock. The opposite view, the "multiregional evolution" model, postulates a gradual, simultaneous transformation of archaic regional human populations into modern ones by gene flow and natural selection. The former view implies that non-African archaic humans contributed nothing or little to the current human gene pool whereas the latter view predicts a genetic continuity in at least some parts of the world. To achieve these two goals, we propose to sequence (a) 250 sequence tagged site (STSs) of 300 bp or longer (single copy sequences) and (b) 10 noncoding regions (each about 10 kb long) in various populations over the world. 3. To develop statistical methods for analyzing DNA polymorphism data, especially for resolving the above controversy and for studying human evolution and population structure in general. We shall consider the effects of recombination, population subdivision, population growth and natural selection, most of which have not been considered in current methods. The new methods and some existing methods will used to analyze the data to be obtained. The new methods will be accessible on the World Wide Web.