Details

Autor(en) / Beteiligte

• KERSTIN, Lindblad- Toh
• GARBER, Manuel
• WARD, Lucas D
• LOWE, Craig B
• HOLLOWAY, Alisha K
• CLAMP, Michele
• GNERRE, Sante
• ALFÖLDI, Jessica
• BEAL, Kathryn
• JEAN CHANG
• CLAWSON, Hiram
• CUFF, James
• ZUK, Or
• PALMA, Federica Di
• FITZGERALD, Stephen
• FLICEK, Paul
• GUTTMAN, Mitchell
• HUBISZ, Melissa J
• JAFFE, David B
• JUNGREIS, Irwin
• JAMES KENT, W
• KOSTKA, Dennis
• LARA, Marcia
• LIN, Michael F
• MARTINS, Andre L
• MASSINGHAM, Tim
• MOLTKE, Ida
• RANEY, Brian J
• RASMUSSEN, Matthew D
• ROBINSON, Jim
• STARK, Alexander
• VILELLA, Albert J
• JIAYU WEN
• XIAOHUI XIE
• PARKER, Brian J
• ZODY, Michael C
• WORLEY, Kim C
• KOVAR, Christie L
• MUZNY, Donna M
• GIBBS, Richard A
• WARREN, Wesley C
• MARDIS, Elaine R
• WEINSTOCK, George M
• WILSON, Richard K
• BIRNEY, Ewan
• WASHIETL, Stefan
• 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
• KHERADPOUR, Pouya
• ERNST, Jason
• JORDAN, Gregory
• MAUCELI, Evan

Titel

A high-resolution map of human evolutionary constraint using 29 mammals

Ist Teil von

• Nature (London), 2011-10, Vol.478 (7370), p.476-482

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Psychology & Behavioral Sciences Collection

Beschreibungen/Notizen

• 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.