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Cited by 825Genomics and Chromatin DynamicsChromosomal and Genetic VariationsGenomics and Phylogenetic Studies

Enhancer Evolution across 20 Mammalian Species

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Villar, Diego, Berthelot, Camille, Aldridge, Sarah, Rayner, Tim F., Lukk, Margus, Pignatelli, Miguel, Park, Thomas J., Deaville, Robert +7 more·2015·Cell
DOI 10.1016/j.cell.2015.01.006PMC PMC4313353
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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.

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  • Enformer's predictions are not limited to conserved enhancers because it does not rely explicitly on nucleotide conservation statistics.

    “by not relying explicitly on nucleotide conservation statistics, as the majority of tools do25, its predictions are not limited to conserved enhancers, which comprise a small proportion of all enhancers30”

    From Effective gene expression prediction from sequence by integrating long-range interactions (2021) · cites this paper as [30]

  • The apparently functionless enhancer-like elements identified in this study reflect evolutionary turnover in cis-acting elements.

    “We would suggest, however, that these elements reflect evolutionary turnover in cis-acting elements as seen in other studies32.”

    From Genetic dissection of the α-globin super-enhancer in vivo (2016) · cites this paper as [32]

  • The prevalence of flexible enhancer organisation is supported by rapid evolutionary turnover of enhancers, which exceeds that of proximal promoter regions.

    “The prevalence of flexible enhancer organisation is also supported by rapid evolutionary turnover of enhancers, which exceeds that of proximal promoter regions [29, 99, 100].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [99]

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Authors
Villar, D., Berthelot, C., Aldridge, S., Rayner, T. F., Lukk, M., Pignatelli, M., Park, T. J., Deaville, R., Erichsen, J. T., Jasinska, A. J., Turner, J. M. A., Bertelsen, M. F., Murchison, E. P., Flicek, P., & Odom, D. T.
Affiliations
  • University of Cambridge (GB)
  • European Bioinformatics Institute (GB)
  • University of Illinois Chicago (US)
  • Zoological Society of London (GB)
  • Cardiff University (GB)
  • University of California, Los Angeles (US)
  • National Institute for Medical Research (GB)
  • Copenhagen Zoo (DK)
Corresponding author
  • Flicek, Paul
  • Odom, Duncan T.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2015-01
Volume
160
Issue
3
Pages
554-566
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2015.01.006
PMC
PMC4313353
OpenAlex
W2095903180
Cited by
825
References
11
Citations by year
2026: 60 · 2025: 68 · 2024: 81 · 2023: 70 · 2022: 84 · 2021: 96 · 2020: 71 · 2019: 94 · 2018: 63 · 2017: 51 · 2016: 54 · 2015: 32
FWCI
28.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
Funders
  • National Science Foundation (WT098051, 0744979)
  • Wellcome Trust (WT095908, WT 098051)
  • European Molecular Biology Laboratory
  • North Carolina Central University
  • Cancer Research UK (15603, WT098051, 20412)
  • Department for Environment, Food and Rural Affairs, UK Government
  • Cardiff University
  • National Institutes of Health (8r01od010980-10, MH060233, OD010965, P40OD010965)
  • Medical Research Council (U117588498)
  • Cancer Research UK Cambridge Institute, University of Cambridge
  • National Institute of Mental Health (R37MH060233)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords
enhancer evolution, promoter evolution, liver gene regulation, H3K27 acetylation, H3K4 trimethylation, positive selection
MeSH terms
Animals, Enhancer Elements, Genetic, Humans, Liver, Mammals, Promoter Regions, Genetic, Transcription Factors, Evolution, Molecular, Histone Code

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