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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-10

AUTHORS

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

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. More... »

PAGES

476

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature10530

    DOI

    http://dx.doi.org/10.1038/nature10530

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1013402885

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21993624


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