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Cell. 2015 Jan 29;160(3):554-66. doi: 10.1016/j.cell.2015.01.006.

Enhancer evolution across 20 mammalian species.

Author information

1
University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.
2
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
3
Department of Biological Sciences, University of Illinois at Chicago (UIC), 845 West Taylor Street, Chicago, IL 60607, USA.
4
UK Cetacean Strandings Investigation Programme (CSIP) and Institute of Zoology, Zoological Society of London, Outer Circle, Regent's Park, London NW1 4RY, UK.
5
School of Optometry and Vision Sciences, Cardiff University, Maindy Road, Cardiff CF24 4HQ, UK.
6
UCLA Center for Neurobehavioral Genetics, 695 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
7
Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
8
Center for Zoo and Wild Animal Health, Copenhagen Zoo, Roskildevej 38, DK-2000 Frederiksberg, Denmark.
9
Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
10
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. Electronic address: flicek@ebi.ac.uk.
11
University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. Electronic address: duncan.odom@cruk.cam.ac.uk.

Abstract

The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution.

PMID:
25635462
PMCID:
PMC4313353
DOI:
10.1016/j.cell.2015.01.006
[Indexed for MEDLINE]
Free PMC Article

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