assessing the evolutionary impact of amino acid mutations in the human genome评估的进化影响氨基酸突变在人类基因组中.pdf

Assessing the Evolutionary Impact of Amino Acid Mutations in the Human Genome 1,2 1 1 1 1 Adam R. Boyko , Scott H. Williamson , Amit R. Indap , Jeremiah D. Degenhardt , Ryan D. Hernandez , 1,2 3 4 5 4 Kirk E. Lohmueller , Mark D. Adams , Steffen Schmidt , John J. Sninsky , Shamil R. Sunyaev , Thomas J. 5 6 2 1 White , Rasmus Nielsen , Andrew G. Clark , Carlos D. Bustamante * 1 Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, United States of America, 2 Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America, 3 Department of Genetics, BRB-624, Case Western Reserve University, Cleveland, Ohio, United States of America, 4 Division of Genetics, Department of Medicine, Brigham Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America, 5 Celera Diagnostics, Alameda, California, United States of America, 6 Center for Comparative Genomics, University of Copenhagen, Copenhagen, Denmark Abstract Quantifying the distribution of fitness effects among newly arising mutations in the human genome is key to resolving important debates in medical and evolutionary genetics. Here, we present a method for inferring this distribution using Single Nucleotide Polymorphism (SNP) data from a population with non-stationary demographic history (such as that of modern humans). Application of our method to 47,576 coding SNPs found by direct resequencing of 11,404 protein coding- gene