Functionally conserved enhancers with divergent sequences in distant vertebrates.

BMC Genomics 2015 Oct 30;16:882. Epub 2015 Oct 30.

Children's Hospital Oakland Research Institute, Oakland, CA, 94609, USA.

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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http://dx.doi.org/10.1186/s12864-015-2070-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628251PMC
October 2015
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References

(Supplied by CrossRef)

N Harmston et al.
Nucleic Acids Res 2013

D Boffelli et al.
Nat Rev Genet 2004

K Lindblad-Toh et al.
Nature 2011

A Woolfe et al.
Genome Biol 2007

D Boffelli et al.
Science 2003

N Ahituv et al.
PLoS Biol 2007

M Friedli et al.
PLoS One 2010

JM Rosin et al.
Hum Mol Genet 2013

L Taher et al.
Genome Res 2011

DM McGaughey et al.
Genome Res 2008

MZ Ludwig et al.
Nature 2000

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