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Repurposing of promoters and enhancers during mammalian evolution

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Carelli, Francesco N., Liechti, Angélica, Halbert, Jean, Warnefors, Maria, Kaessmann, Henrik·2018·Nature Communications
DOI 10.1038/s41467-018-06544-zPMC PMC6172195

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Abstract

Promoters and enhancers—key controllers of gene expression—have long been distinguished from each other based on their function. However, recent work suggested that common architectural and functional features might have facilitated the conversion of one type of element into the other during evolution. Here, based on cross-mammalian analyses of epigenome and transcriptome data, we provide support for this hypothesis by detecting 445 regulatory elements with signatures of activity turnover (termed P/E elements). Most events represent transformations of putative ancestral enhancers into promoters, leading to the emergence of species-specific transcribed loci or 5′ exons. Distinct GC sequence compositions and stabilizing 5′ splicing (U1) regulatory motif patterns may have predisposed P/E elements to regulatory repurposing, and changes in the U1 and polyadenylation signal densities and distributions likely drove the evolutionary activity switches. Our work suggests that regulatory repurposing facilitated regulatory innovation and the origination of new genes and exons during evolution.

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  • Promoters are sometimes repurposed into enhancers, but at a 13-fold lower rate than enhancer-to-promoter repurposing.

    “Promoters are also sometimes repurposed into enhancers, but at a 13-fold lower rate than enhancer-to-promoter [100].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [100]

    The Results section, ‘Enhancers are the main source of regulatory repurposing’ (page not specified), reports promoter-to-enhancer repurposing and an approximately 13-fold enrichment in the opposite direction after accounting for enhancer loss. It does not report a 13-fold difference in the raw repurposing rates: that difference was approximately 26-fold in the primate liver analysis. The comparable enrichment in glires was approximately sixfold and not statistically significant. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • 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 [100]

  • Some enhancers have undergone genetic mutations allowing them to be repurposed into gene promoters in mammals.

    “The “grey area” between enhancers and promoters is supported by evolutionary evidence that some enhancers have undergone genetic mutations allowing them to be repurposed into gene promoters in mammals [100].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [100]

  • Enhancers predisposed to convert into promoters may have a particular GC sequence composition and presence of 5′ splicing regulatory motif patterns.

    “Therefore, enhancers predisposed to convert into promoters may have a particular GC sequence composition and presence of 5′ splicing regulatory motif patterns [100].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [100]

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Research works printed but not linked: 52

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Cited by

Sorted by citations

Authors
Carelli, F. N., Liechti, A., Halbert, J., Warnefors, M., & Kaessmann, H.
Affiliations
  • University of Cambridge (GB)
  • University of Lausanne (CH)
  • Heidelberg University (DE)
Corresponding author
  • Carelli, Francesco N.
  • Kaessmann, Henrik
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-10-04
Volume
9
Issue
1
Pages
4066-4066
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-018-06544-z
PMC
PMC6172195
OpenAlex
W2892647771
Cited by
66
References
9
Citations by year
2026: 4 · 2025: 3 · 2024: 4 · 2023: 12 · 2022: 6 · 2021: 14 · 2020: 8 · 2019: 10 · 2018: 4
FWCI
3.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (publishedVersion, other-oa)
  • IRIS (submittedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
EC | European Research Council (615253)
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 › RNA Research and Splicing
Keywords
promoter evolution, enhancer evolution, mammalian evolution, polyadenylation signal, GC content, regulatory innovation
MeSH terms
Animals, Enhancer Elements, Genetic, Primates, Promoter Regions, Genetic, Rodentia, Evolution, Molecular

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