A High-Resolution Map of Human Evolutionary Constraint Using 29 Mammals
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2012
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| Online Access: | http://hdl.handle.net/1721.1/72595 https://orcid.org/0000-0002-8017-809X |
| _version_ | 1826216494520860672 |
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| author | Mag Washietl, Stefan Kheradpour, Pouya Ernst, Jason Ward, Lucas D. Jungreis, Irwin Rasmussen, Matthew D. Kellis, Manolis |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Mag Washietl, Stefan Kheradpour, Pouya Ernst, Jason Ward, Lucas D. Jungreis, Irwin Rasmussen, Matthew D. Kellis, Manolis |
| author_sort | Mag Washietl, Stefan |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:48:37Z |
| format | Article |
| id | mit-1721.1/72595 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:48:37Z |
| publishDate | 2012 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/725952022-09-29T21:37:38Z A High-Resolution Map of Human Evolutionary Constraint Using 29 Mammals Mag Washietl, Stefan Kheradpour, Pouya Ernst, Jason Ward, Lucas D. Jungreis, Irwin Rasmussen, Matthew D. Kellis, Manolis Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Kellis, Manolis Mag Washietl, Stefan Kheradpour, Pouya Ernst, Jason Ward, Lucas D. Jungreis, Irwin Rasmussen, Matthew D. Kellis, Manolis 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. National Human Genome Research Institute (U.S.) National Institute of General Medical Sciences (U.S.) (Grant number GM82901) National Science Foundation (U.S.). Postdoctural Fellowship (Award 0905968) National Science Foundation (U.S.). Career (0644282) National Institutes of Health (U.S.) (R01-HG004037) Alfred P. Sloan Foundation. Austrian Science Fund. Erwin Schrodinger Fellowship 2012-09-10T16:10:55Z 2012-09-10T16:10:55Z 2011-10 2011-01 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/72595 Lindblad-Toh, Kerstin et al. “A High-resolution Map of Human Evolutionary Constraint Using 29 Mammals.” Nature 478.7370 (2011): 476–482. https://orcid.org/0000-0002-8017-809X en_US http://dx.doi.org/10.1038/nature10530 Nature Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Nature Publishing Group PubMed Central |
| spellingShingle | Mag Washietl, Stefan Kheradpour, Pouya Ernst, Jason Ward, Lucas D. Jungreis, Irwin Rasmussen, Matthew D. Kellis, Manolis A High-Resolution Map of Human Evolutionary Constraint Using 29 Mammals |
| title | A High-Resolution Map of Human Evolutionary Constraint Using 29 Mammals |
| title_full | A High-Resolution Map of Human Evolutionary Constraint Using 29 Mammals |
| title_fullStr | A High-Resolution Map of Human Evolutionary Constraint Using 29 Mammals |
| title_full_unstemmed | A High-Resolution Map of Human Evolutionary Constraint Using 29 Mammals |
| title_short | A High-Resolution Map of Human Evolutionary Constraint Using 29 Mammals |
| title_sort | high resolution map of human evolutionary constraint using 29 mammals |
| url | http://hdl.handle.net/1721.1/72595 https://orcid.org/0000-0002-8017-809X |
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