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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM055759-02
Application #
2857294
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1998-01-01
Project End
2001-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Chicago
Department
Biology
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Yu, Ning; Jensen-Seaman, Michael I; Chemnick, Leona et al. (2004) Nucleotide diversity in gorillas. Genetics 166:1375-83
Cavalcanti, Andre R O; Ferreira, Ricardo; Gu, Zhenglong et al. (2003) Patterns of gene duplication in Saccharomyces cerevisiae and Caenorhabditis elegans. J Mol Evol 56:28-37
Jensen-Seaman, Michael I; Li, Wen-Hsiung (2003) Evolution of the hominoid semenogelin genes, the major proteins of ejaculated semen. J Mol Evol 57:261-70
Li, Wen-Hsiung; Gu, Zhenglong; Cavalcanti, Andre R O et al. (2003) Detection of gene duplications and block duplications in eukaryotic genomes. J Struct Funct Genomics 3:27-34
Yu, Ning; Jensen-Seaman, Michael I; Chemnick, Leona et al. (2003) Low nucleotide diversity in chimpanzees and bonobos. Genetics 164:1511-8
Li, Haipeng; Zhang, Yunwu; Zhang, Ya-Ping et al. (2003) Neutrality tests using DNA polymorphism from multiple samples. Genetics 163:1147-51
Nekrutenko, Anton; Makova, Kateryna D; Li, Wen-Hsiung (2002) The K(A)/K(S) ratio test for assessing the protein-coding potential of genomic regions: an empirical and simulation study. Genome Res 12:198-202
Yi, Soojin; Ellsworth, Darrell L; Li, Wen-Hsiung (2002) Slow molecular clocks in Old World monkeys, apes, and humans. Mol Biol Evol 19:2191-8
Gu, Zhenglong; Cavalcanti, Andre; Chen, Feng-Chi et al. (2002) Extent of gene duplication in the genomes of Drosophila, nematode, and yeast. Mol Biol Evol 19:256-62
Yu, Ning; Chen, Feng-Chi; Ota, Satoshi et al. (2002) Larger genetic differences within africans than between Africans and Eurasians. Genetics 161:269-74

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