A High-Resolution Map of Human Evolutionary Constraint Using 29 Mammals
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Kellis_A high-resolution map.pdf
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Author(s)
Mag Washietl, Stefan
Kheradpour, Pouya
Ernst, Jason
Ward, Lucas D.
Jungreis, Irwin
Rasmussen, Matthew D.
Kellis, Manolis
Date Issued
October 2011
Journal
Nature
Publisher
Nature Publishing Group
Citation
Lindblad-Toh, Kerstin et al. “A High-resolution Map of Human Evolutionary Constraint Using 29 Mammals.” Nature 478.7370 (2011): 476–482.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1038/nature10530
