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- Title
A high-resolution map of human evolutionary constraint using 29 mammals.
- Authors
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
- 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.
- Subjects
HUMAN evolution; HUMAN genome; AMINO acid sequence; MAMMALOGICAL research; EXONS (Genetics); NON-coding RNA
- Publication
Nature, 2011, Vol 478, Issue 7370, p476
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature10530