Forskning ved Københavns Universitet - Københavns Universitet


A high-resolution map of human evolutionary constraint using 29 mammals

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Kerstin Lindblad-Toh, Manuel Garber, Or Zuk, Michael F Lin, Brian J Parker, Gregory Jordan, Evan Mauceli, Lucas D Ward, Craig B Lowe, Alisha K Holloway, Michele Clamp, Sante Gnerre, Ida Moltke, Jiayu Wen, Jakob Skou Pedersen

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.
Udgave nummer7370
Sider (fra-til)476-82
Antal sider7
StatusUdgivet - 27 okt. 2011

ID: 35188003