A high-resolution map of human evolutionary constraint using 29 mammals.
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.
Type
Journal articleSubject
Broad Institute Sequencing Platform and Whole Genome Assembly TeamBaylor College of Medicine Human Genome Sequencing Center Sequencing Team
Genome Institute at Washington University
Animals
Mammals
Humans
Disease
RNA
Sequence Alignment
Sequence Analysis, DNA
Genomics
Evolution, Molecular
Phylogeny
Genome
Genome, Human
Exons
Health
Selection, Genetic
Molecular Sequence Annotation
Permalink
https://hdl.handle.net/10161/17408Published Version (Please cite this version)
10.1038/nature10530Publication Info
Lindblad-Toh, Kerstin; Garber, Manuel; Zuk, Or; Lin, Michael F; Parker, Brian J; Washietl,
Stefan; ... Kellis, Manolis (2011). A high-resolution map of human evolutionary constraint using 29 mammals. Nature, 478(7370). pp. 476-482. 10.1038/nature10530. Retrieved from https://hdl.handle.net/10161/17408.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Craig Lowe
Assistant Professor of Molecular Genetics and Microbiology

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
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