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Enhancer evolution across 20 mammalian species.

Diego Villar1, Camille Berthelot2, Sarah Aldridge1

  • 1University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.

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|January 31, 2015
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Summary

Regulatory evolution in mammals shows rapid enhancer changes, often from ancestral DNA exaptation, while liver promoters remain conserved. This reveals key insights into mammalian genome functional genetics.

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Area of Science:

  • Genomics
  • Evolutionary Biology
  • Molecular Biology

Background:

  • Mammalian radiation coincided with rapid genomic changes, particularly in noncoding regions.
  • A comprehensive understanding of mammalian regulatory evolution is lacking.

Purpose of the Study:

  • To investigate the evolutionary dynamics of promoters and enhancers in the mammalian liver.
  • To identify mechanisms driving regulatory evolution across diverse mammalian species.

Main Methods:

  • Profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation.
  • Comparative analysis across 20 mammalian species from six diverse orders.

Main Results:

  • Rapid evolution of enhancers is a universal characteristic of mammalian genomes.
  • Most new enhancers originate from ancestral DNA exaptation, not repeat element expansion.
  • Liver promoters are largely conserved across the studied mammalian species.
  • Recently evolved enhancers can be linked to genes under positive selection.

Conclusions:

  • Enhancer evolution, primarily through DNA exaptation, is a major driver of mammalian regulatory adaptation.
  • Promoter conservation suggests a stable regulatory framework for essential liver functions.
  • This study provides a framework for annotating regulatory adaptations and understanding functional genetics in mammalian evolution.