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Cited by 27Genomics and Chromatin DynamicsChromosomal and Genetic VariationsDevelopmental Biology and Gene Regulation

Functionally conserved enhancers with divergent sequences in distant vertebrates

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Yang, Song, Oksenberg, Nir, Takayama, Sachiko, Heo, Seok-Jin, Poliakov, Alexander, Ahituv, Nadav, Dubchak, Inna, Boffelli, Dario·2015·BMC Genomics
DOI 10.1186/s12864-015-2070-7PMC PMC4628251
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Abstract

BACKGROUND: To examine the contributions of sequence and function conservation in the evolution of enhancers, we systematically identified enhancers whose sequences are not conserved among distant groups of vertebrate species, but have homologous function and are likely to be derived from a common ancestral sequence. Our approach combined comparative genomics and epigenomics to identify potential enhancer sequences in the genomes of three groups of distantly related vertebrate species. RESULTS: We searched for sequences that were conserved within groups of closely related species but not between groups of more distant species, and were associated with an epigenetic mark of enhancer activity. To facilitate inferring orthology between non-conserved sequences, we limited our search to introns whose orthology could be unambiguously established by mapping the bracketing exons. We show that a subset of these non-conserved but syntenic sequences from the mouse and zebrafish genomes have homologous functions in a zebrafish transgenic enhancer assay. The conserved expression patterns driven by these enhancers are probably associated with short transcription factor-binding motifs present in the divergent sequences. CONCLUSIONS: We have identified numerous potential enhancers with divergent sequences but a conserved function. These results indicate that selection on function, rather than sequence, may be a common mode of enhancer evolution; evidence for selection at the sequence level is not a necessary criterion to define a gene regulatory element.

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  • Homologous enhancers in a pair of distantly related species can retain their function in the non-host organism despite differences in DNA sequence.

    “Consistent with this, homologous enhancers in a pair of distantly related species can retain their function in the non-host organism despite differences in DNA sequence [101, 110, 111].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [110]

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Cites

  • Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes

    Siepel, A., Bejerano, G., Pedersen, J. S., Hinrichs, A. S., Hou, M., Rosenbloom, K., Clawson, H., Spieth, J., Hillier, L. W., Richards, S., et al. (2005) · Genome Research · doi:10.1101/gr.3715005 · Cited by 4,408 · cited 4× · see citing works

    “Evolutionarily conserved sequences Evolutionarily conserved elements in the reference genomes were derived from the intra-group multiple alignments using PhastCons [40], that is based on phyloHMM, a statistical model of sequence evolution.”
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Authors
Yang, S., Oksenberg, N., Takayama, S., Heo, S.-J., Poliakov, A., Ahituv, N., Dubchak, I., & Boffelli, D.
Affiliations
  • Lawrence Berkeley National Laboratory (US)
  • University of California, San Francisco (US)
  • Joint Genome Institute (US)
Corresponding author
  • Dubchak, Inna
  • Boffelli, Dario
ORCID
Venue
BMC Genomics
Publisher
Springer Science and Business Media LLC
Published
2015-10-30
Volume
16
Issue
1
Pages
882-882
ISSN
1471-2164 (ISSN-L)
DOI
10.1186/s12864-015-2070-7
PMC
PMC4628251
OpenAlex
W1934801000
Cited by
27
References
1
Citations by year
2026: 4 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 3
FWCI
1.30
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Genomics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • National Heart, Lung, and Blood Institute (HL091495)
  • Office of Science (DE-AC02-05CH11231)
  • National Human Genome Research Institute (R01HG005058, 1R01HG006768)
  • National Institute of Child Health and Human Development (R01HD059862)
  • National Institute of General Medical Sciences (GM61390)
  • National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK090382)
  • National Institute of Neurological Disorders and Stroke (1R01NS079231)
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 › Developmental Biology and Gene Regulation
Keywords
enhancer evolution, sequence conservation, orthology, transcription factor binding motifs, gene regulatory elements, mice, zebrafish, comparative genomics, epigenomics
MeSH terms
Animals, Binding Sites, Enhancer Elements, Genetic, Protein Binding, Transcription Factors, Genetic Variation, Vertebrates, Reproducibility of Results, Conserved Sequence, Evolution, Molecular, Computational Biology, Gene Expression Profiling, Animals, Genetically Modified, Genome-Wide Association Study, Position-Specific Scoring Matrices, Nucleotide Motifs

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