Natural selection on protein-coding genes in the human genome Export

@article{citeulike:355574, abstract = {Comparisons of DNA polymorphism within species to divergence between species enables the discovery of molecular adaptation in evolutionarily constrained genes as well as the differentiation of weak from strong purifying selection1, 2, 3, 4. The extent to which weak negative and positive darwinian selection have driven the molecular evolution of different species varies greatly5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, with some species, such as Drosophila melanogaster, showing strong evidence of pervasive positive selection6, 7, 8, 9, and others, such as the selfing weed Arabidopsis thaliana, showing an excess of deleterious variation within local populations9, 10. Here we contrast patterns of coding sequence polymorphism identified by direct sequencing of 39 humans for over 11,000 genes to divergence between humans and chimpanzees, and find strong evidence that natural selection has shaped the recent molecular evolution of our species. Our analysis discovered 304 (9.0\%) out of 3,377 potentially informative loci showing evidence of rapid amino acid evolution. Furthermore, 813 (13.5\%) out of 6,033 potentially informative loci show a paucity of amino acid differences between humans and chimpanzees, indicating weak negative selection and/or balancing selection operating on mutations at these loci. We find that the distribution of negatively and positively selected genes varies greatly among biological processes and molecular functions, and that some classes, such as transcription factors, show an excess of rapidly evolving genes, whereas others, such as cytoskeletal proteins, show an excess of genes with extensive amino acid polymorphism within humans and yet little amino acid divergence between humans and chimpanzees.}, author = {Bustamante, Carlos D. and Fledel-Alon, Adi and Williamson, Scott and Nielsen, Rasmus and Todd Hubisz, Melissa and Glanowski, Stephen and Tanenbaum, David M. and White, Thomas J. and Sninsky, John J. and Hernandez, Ryan D. and Civello, Daniel and Adams, Mark D. and Cargill, Michele and Clark, Andrew G.}, citeulike-article-id = {355574}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature04240}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature04240}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16237444}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16237444}, day = {20}, doi = {10.1038/nature04240}, issn = {0028-0836}, journal = {Nature}, keywords = {acceleration, genomics, human\_biodiversity, human\_evolution}, month = {October}, number = {7062}, pages = {1153--1157}, posted-at = {2008-06-18 22:38:13}, priority = {4}, publisher = {Nature Publishing Group}, title = {Natural selection on protein-coding genes in the human genome}, url = {http://dx.doi.org/10.1038/nature04240}, volume = {437}, year = {2005} }

TY - JOUR ID - citeulike:355574 L3 - citeulike-article-id:355574 N2 - Comparisons of DNA polymorphism within species to divergence between species enables the discovery of molecular adaptation in evolutionarily constrained genes as well as the differentiation of weak from strong purifying selection1, 2, 3, 4. The extent to which weak negative and positive darwinian selection have driven the molecular evolution of different species varies greatly5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, with some species, such as Drosophila melanogaster, showing strong evidence of pervasive positive selection6, 7, 8, 9, and others, such as the selfing weed Arabidopsis thaliana, showing an excess of deleterious variation within local populations9, 10. Here we contrast patterns of coding sequence polymorphism identified by direct sequencing of 39 humans for over 11,000 genes to divergence between humans and chimpanzees, and find strong evidence that natural selection has shaped the recent molecular evolution of our species. Our analysis discovered 304 (9.0%) out of 3,377 potentially informative loci showing evidence of rapid amino acid evolution. Furthermore, 813 (13.5%) out of 6,033 potentially informative loci show a paucity of amino acid differences between humans and chimpanzees, indicating weak negative selection and/or balancing selection operating on mutations at these loci. We find that the distribution of negatively and positively selected genes varies greatly among biological processes and molecular functions, and that some classes, such as transcription factors, show an excess of rapidly evolving genes, whereas others, such as cytoskeletal proteins, show an excess of genes with extensive amino acid polymorphism within humans and yet little amino acid divergence between humans and chimpanzees. IS - 7062 JF - Nature SN - 0028-0836 EP - 1157 TI - Natural selection on protein-coding genes in the human genome PB - Nature Publishing Group VL - 437 SP - 1153 KW - acceleration KW - genomics KW - human_biodiversity KW - human_evolution AU - Bustamante, Carlos AU - Fledel-Alon, Adi AU - Williamson, Scott AU - Nielsen, Rasmus AU - Todd Hubisz, Melissa AU - Glanowski, Stephen AU - Tanenbaum, David AU - White, Thomas AU - Sninsky, John AU - Hernandez, Ryan AU - Civello, Daniel AU - Adams, Mark AU - Cargill, Michele AU - Clark, Andrew PY - 2005/10/20/ UR - http://dx.doi.org/10.1038/nature04240 ER -