HUMAN DNA POLYMORPHISM AND EVOLUTION

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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.