Title | A high-resolution map of human evolutionary constraint using 29 mammals. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Lindblad-Toh, K, Garber, M, Zuk, O, Lin, MF, Parker, BJ, Washietl, S, Kheradpour, P, Ernst, J, Jordan, G, Mauceli, E, Ward, LD, Lowe, CB, Holloway, AK, Clamp, M, Gnerre, S, Alföldi, J, Beal, K, Chang, J, Clawson, H, Cuff, J, Di Palma, F, Fitzgerald, S, Flicek, P, Guttman, M, Hubisz, MJ, Jaffe, DB, Jungreis, I, W Kent, J, Kostka, D, Lara, M, Martins, AL, Massingham, T, Moltke, I, Raney, BJ, Rasmussen, MD, Robinson, J, Stark, A, Vilella, AJ, Wen, J, Xie, X, Zody, MC, Baldwin, J, Bloom, T, Chin, CWhye, Heiman, D, Nicol, R, Nusbaum, C, Young, S, Wilkinson, J, Worley, KC, Kovar, CL, Muzny, DM, Gibbs, RA, Cree, A, Dihn, HH, Fowler, G, Jhangiani, S, Joshi, V, Lee, S, Lewis, LR, Nazareth, LV, Okwuonu, G, Santibanez, J, Warren, WC, Mardis, ER, Weinstock, GM, Wilson, RK, Delehaunty, K, Dooling, D, Fronik, C, Fulton, L, Fulton, B, Graves, T, Minx, P, Sodergren, E, Birney, E, Margulies, EH, Herrero, J, Green, ED, Haussler, D, Siepel, A, Goldman, N, Pollard, KS, Pedersen, JS, Lander, ES, Kellis, M |
Corporate Authors | Broad Institute Sequencing Platform and Whole Genome Assembly Team, Baylor College of Medicine Human Genome Sequencing Center Sequencing Team, Genome Institute at Washington University |
Journal | Nature |
Volume | 478 |
Issue | 7370 |
Pagination | 476-82 |
Date Published | 2011 Oct 12 |
ISSN | 1476-4687 |
Keywords | Animals, Disease, Evolution, Molecular, Exons, Genome, Genome, Human, Genomics, Health, Humans, Mammals, Molecular Sequence Annotation, Phylogeny, RNA, Selection, Genetic, Sequence Alignment, Sequence Analysis, DNA |
Abstract | The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease. |
DOI | 10.1038/nature10530 |
Alternate Journal | Nature |
PubMed ID | 21993624 |
PubMed Central ID | PMC3207357 |
Grant List | R01 HG004037 / HG / NHGRI NIH HHS / United States R01 HG003474 / HG / NHGRI NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States U54 HG003273 / HG / NHGRI NIH HHS / United States GM82901 / GM / NIGMS NIH HHS / United States 095908 / / Wellcome Trust / United Kingdom U54 HG003067-09 / HG / NHGRI NIH HHS / United States R01 GM082901 / GM / NIGMS NIH HHS / United States U54 HG003067 / HG / NHGRI NIH HHS / United States |
A high-resolution map of human evolutionary constraint using 29 mammals.
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