A high-resolution map of human evolutionary constraint using 29 mammals.
In: Nature, Jg. 478 (2011-10-12), Heft 7370
academicJournal
- 476 - 482
Zugriff:
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.
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A high-resolution map of human evolutionary constraint using 29 mammals.
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Autor/in / Beteiligte Person: | Lindblad-Toh, Kerstin ; Garber, Manuel ; Zuk, Or ; Lin, Michael F ; Parker, Brian J ; Washietl, Stefan ; Kheradpour, Pouya ; Ernst, Jason ; Jordan, Gregory ; Mauceli, Evan ; Ward, Lucas D ; Lowe, Craig B ; Holloway, Alisha K ; Clamp, Michele ; Gnerre, Sante ; Alföldi, Jessica ; Beal, Kathryn ; Chang, Jean ; Clawson, Hiram ; Cuff, James ; Di Palma, Federica ; Fitzgerald, Stephen ; Flicek, Paul ; Guttman, Mitchell ; Hubisz, Melissa J ; Jaffe, David B ; Jungreis, Irwin ; Kent, W James ; Kostka, Dennis ; Lara, Marcia ; Martins, Andre L ; Massingham, Tim ; Moltke, Ida ; Raney, Brian J ; Rasmussen, Matthew D ; Robinson, Jim ; Stark, Alexander ; Vilella, Albert J ; Wen, Jiayu ; Xie, Xiaohui ; Zody, Michael C ; Broad Institute Sequencing Platform and Whole Genome Assembly Team ; Baldwin, Jen ; Bloom, Toby ; Chin, Chee Whye ; Heiman, Dave ; Nicol, Robert ; Nusbaum, Chad ; Young, Sarah ; Wilkinson, Jane ; Worley, Kim C ; Kovar, Christie L ; Muzny, Donna M ; Gibbs, Richard A ; Baylor College of Medicine Human Genome Sequencing Center Sequencing Team ; Cree, Andrew ; Dihn, Huyen H ; Fowler, Gerald ; Jhangiani, Shalili ; Joshi, Vandita ; Lee, Sandra ; Lewis, Lora R ; Nazareth, Lynne V ; Okwuonu, Geoffrey ; Santibanez, Jireh ; Warren, Wesley C ; Mardis, Elaine R ; Weinstock, George M ; Wilson, Richard K ; Genome Institute at Washington University ; Delehaunty, Kim ; Dooling, David ; Fronik, Catrina ; Fulton, Lucinda ; Fulton, Bob ; Graves, Tina ; Minx, Patrick ; Sodergren, Erica ; Birney, Ewan ; Margulies, Elliott H ; Herrero, Javier ; Green, Eric D ; Haussler, David ; Siepel, Adam ; Goldman, Nick ; Pollard, Katherine S ; Pedersen, Jakob S ; Lander, Eric S ; Kellis, Manolis |
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Zeitschrift: | Nature, Jg. 478 (2011-10-12), Heft 7370 |
Veröffentlichung: | eScholarship, University of California, 2011 |
Medientyp: | academicJournal |
Umfang: | 476 - 482 |
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