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Functionally conserved enhancers with divergent sequences in distant vertebrates.

Song Yang1, Nir Oksenberg2,3, Sachiko Takayama4

  • 1Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA. syang@enders.tch.harvard.edu.

BMC Genomics
|November 1, 2015
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Summary
This summary is machine-generated.

Evolutionary enhancers can retain function despite sequence divergence. This study found non-conserved sequences with homologous enhancer functions, suggesting functional selection drives evolution.

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Area of Science:

  • Genomics
  • Evolutionary Biology
  • Molecular Biology

Background:

  • Investigating the evolution of gene regulatory elements, specifically enhancers.
  • Examining the interplay between sequence conservation and functional conservation in enhancer evolution.
  • Focusing on enhancers with non-conserved sequences but homologous functions across distant vertebrate species.

Purpose of the Study:

  • To systematically identify and characterize enhancers that have diverged in sequence but maintained conserved function.
  • To understand the evolutionary mechanisms driving enhancer innovation and conservation.
  • To determine if functional selection, rather than sequence conservation, is a primary driver of enhancer evolution.

Main Methods:

  • Combined comparative genomics and epigenomics to identify potential enhancer sequences in vertebrate genomes.
  • Searched for sequences conserved within closely related species but not between distant species, linked to enhancer activity marks.
  • Utilized introns with unambiguously established orthology via flanking exons for analysis.
  • Employed a zebrafish transgenic enhancer assay to test the function of identified non-conserved sequences.

Main Results:

  • Identified numerous potential enhancers with divergent sequences but conserved functions across species.
  • Demonstrated that a subset of non-conserved, syntenic sequences from mouse and zebrafish exhibit homologous functions in vivo.
  • Found that conserved expression patterns are likely driven by conserved short transcription factor-binding motifs within divergent sequences.

Conclusions:

  • Highlighted that enhancers can evolve through sequence divergence while maintaining functional conservation.
  • Indicated that selection on function, not necessarily sequence, is a significant mode of enhancer evolution.
  • Established that sequence-level conservation is not a prerequisite for defining a gene regulatory element.