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A high-resolution map of human evolutionary constraint using 29 mammals
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2011 (English)In: Nature, ISSN 0028-0836, Vol. 478, no 7370, 476-482 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2011. Vol. 478, no 7370, 476-482 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-161456DOI: 10.1038/nature10530ISI: 000296194200035OAI: oai:DiVA.org:uu-161456DiVA: diva2:456564
Available from: 2011-11-15 Created: 2011-11-14 Last updated: 2011-11-15Bibliographically approved

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Lindblad-Toh, Kerstin
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