A high-resolution map of human evolutionary constraint using 29 mammals
2011 (English)In: Nature, ISSN 0028-0836, Vol. 478, no 7370, 476-482 p.Article in journal (Refereed) Published
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.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-161456DOI: 10.1038/nature10530ISI: 000296194200035OAI: oai:DiVA.org:uu-161456DiVA: diva2:456564