• D Villar, C Berthelot, S Aldridge, TF Rayner, M Lukk, M Pignatelli, TJ Park, R Deaville, JT Erichsen, AJ Jasinska, JMA Turner, MF Bertelsen, EP Murchison, P Flicek, DT Odom. Enhancer Evolution across 20 Mammalian Species. Cell 2015;160(3):554–566. doi:10.1016/j.cell.2015.01.006
  [BibTeX] [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

  @Article{25635462,
  author = {Villar D and Berthelot C and Aldridge S and Rayner TF and Lukk M and Pignatelli M and Park TJ and Deaville R and Erichsen JT and Jasinska AJ and Turner JMA and Bertelsen MF and Murchison EP and Flicek P and Odom DT},
  title = {Enhancer Evolution across 20 Mammalian Species},
  journal = {Cell},
  volume = {160},
  number = {3},
  pages = {554--566},
  year = {2015},
  doi = {10.1016/j.cell.2015.01.006},
  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},}

Description

The mammalian radiation has corresponded with rapid changes in the noncoding 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 twenty mammals from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report rapid evolution of enhancers as a universal feature of mammalian genomes: across all study species half of all liver enhancers are unique to a single species. Most of these recently-evolved enhancers arise from exaptation of ancestral DNA, and not from lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across our study species. Recently-evolved enhancers can be significantly associated with genes under positive selection, demonstrating a powerful approach to annotating regulatory adaptations in newly sequenced genomes. These results provide unprecedented insight into the functional genetics underpinning mammalian regulatory evolution.

Raw Data

The raw chip-seq data for H3K4me3 and H3K27ac from the 20 mammalian species species can be found in ArrayExpress with the accession number  E-MTAB-2633.

ChIP-seq peaks

Consensus MACS peaks reproducible across two or more biological replicates for H3K4me3 and H3K27ac can be found in ArrayExpress with the accession number  E-MTAB-2633.
The format used for the consensus peak files is a custom bed file, with columns as detailed below (tab-separated):
[Chromosome] [Start] [End] [Unique Peak Identifier]

Combined peak calls for H3K4me3, H3K4me3&H3K27ac or H3K27ac in each species can be found at  Combined Peak Calls  with columns as follows (tab-separated):
[Chromosome] [Start] [End] [Identifiers of combined peaks, separated by slashes]

Highly conserved promoters and enhancers

The folder below contains BED files of highly conserved promoters and enhancers identified in the study:

Highly Conserved Elements

Columns are as follows (tab-separated; see header for exact column-matching to species):
[Human chromosome] [Human Start] [Human End] [Human Identifier] [Identifier in species 1] … [Identifier in species 20]

When the reference region in human could be  mapped  in another species but the activity of the region was  not conserved  in this species, the species’ column contains a dash (“-“).
When the reference region in human could  not be mapped  in another species (no alignment), this species’ column is marked as not available (“NA”).

Classification into promoters and enhancers was based on the histone marking observed across the majority of species, and may not always be in agreement with the marking found in the reference human region.

Lineage-specific promoters and enhancers

The folder below contains BED files of lineage-specific promoters and enhancers identified in primates, rodents, ungulates and carnivores, with column headers as above:

Lineage-specific Elements

Different lineages use different reference species, and the reference species is listed in the file name. Column counts vary depending on available alignments between the reference species and the other study species.

Recently evolved promoters and enhancers

The folder below contains BED files of recently-evolved promoters and enhancers identified in human, mouse, cow, dog, naked mole rat and dolphin, with column headers as above:

Recently Evolved Elements

Conservation of human, mouse, cow and dog promoters and enhancers

The folder below contains BED files of all promoters and enhancers identified in human, mouse, cow and dog, and their conservation in other species, with column headers as above:

Conservation

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