2004 Population history and natural selection shape patterns of genetic variation in 132 genes.pdfVIP

Open access, freely available online PLoS BIOLOGY Population History and Natural Selection Shape Patterns of Genetic Variation in 132 Genes 1* 1 2 2 3 Joshua M. Akey , Michael A. Eberle , Mark J. Rieder , Christopher S. Carlson , Mark D. Shriver , Deborah A. Nickerson2, Leonid Kruglyak1,4* 1 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America, 2 Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America, 3 Department of Anthropology, Pennsylvania State University, University Park, Pennsylvania, United States of America, 4 Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America Identifying regions of the human genome that have been targets of natural selection will provide important insights into human evolutionary history and may facilitate the identification of complex disease genes. Although the signature that natural selection imparts on DNA sequence variation is difficult to disentangle from the effects of neutral processes such as population demographic history, selective and demographic forces can be distinguished by analyzing multiple loci dispersed throughout the genome. We studied the molecular evolution of 132 genes by comprehensively resequencing them in 24 African-Americans and 23 European-Americans. We developed a rigorous computational approach for taking into account multiple hypothesis tests and demographic history and found that while many apparent selective events can instead be explained by demography, there is also strong evidence for positive or balancing selection at eight genes in the European-American population, but none in the African-American popu