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

Lindblad-Toh, Kerstin (author)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
Garber, Manuel (author)
Zuk, Or (author)
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Lin, Michael F. (author)
Parker, Brian J. (author)
Washietl, Stefan (author)
Kheradpour, Pouya (author)
Ernst, Jason (author)
Jordan, Gregory (author)
Mauceli, Evan (author)
Ward, Lucas D. (author)
Lowe, Craig B. (author)
Holloway, Alisha K. (author)
Clamp, Michele (author)
Gnerre, Sante (author)
Alfoeldi, Jessica (author)
Beal, Kathryn (author)
Chang, Jean (author)
Clawson, Hiram (author)
Cuff, James (author)
Di Palma, Federica (author)
Fitzgerald, Stephen (author)
Flicek, Paul (author)
Guttman, Mitchell (author)
Hubisz, Melissa J. (author)
Jaffe, David B. (author)
Jungreis, Irwin (author)
Kent, W. James (author)
Kostka, Dennis (author)
Lara, Marcia (author)
Martins, Andre L. (author)
Massingham, Tim (author)
Moltke, Ida (author)
Raney, Brian J. (author)
Rasmussen, Matthew D. (author)
Robinson, Jim (author)
Stark, Alexander (author)
Vilella, Albert J. (author)
Wen, Jiayu (author)
Xie, Xiaohui (author)
Zody, Michael C. (author)
Worley, Kim C. (author)
Kovar, Christie L. (author)
Muzny, Donna M. (author)
Gibbs, Richard A. (author)
Warren, Wesley C. (author)
Mardis, Elaine R. (author)
Weinstock, George M. (author)
Wilson, Richard K. (author)
Birney, Ewan (author)
Margulies, Elliott H. (author)
Herrero, Javier (author)
Green, Eric D. (author)
Haussler, David (author)
Siepel, Adam (author)
Goldman, Nick (author)
Pollard, Katherine S. (author)
Pedersen, Jakob S. (author)
Lander, Eric S. (author)
Kellis, Manolis (author)
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 (creator_code:org_t)
2011-10-12
2011
English.
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 478:7370, s. 476-482
Related links:
https://www.nature.c...
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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 similar to 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for similar to 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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