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Updated: May 6, 2026

A Rapid In Vivo Bioassay for Developmentally Active Enhancers
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Many human accelerated regions are developmental enhancers.

John A Capra1, Genevieve D Erwin, Gabriel McKinsey

  • 1Gladstone Institutes, University of California, , San Francisco, CA 94158, USA.

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
|November 13, 2013
PubMed
Summary

Researchers identified human-specific gene regulatory elements called non-coding human accelerated regions (ncHARs). These ncHARs may explain unique human developmental traits by altering gene expression patterns during embryonic development.

Keywords:
developmentenhancersgene regulationhuman accelerated regionsprimate evolution

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Area of Science:

  • Genomics
  • Evolutionary Biology
  • Developmental Biology

Background:

  • Human evolution is characterized by significant differences in form and function compared to other primates.
  • Gene regulatory changes are believed to play a crucial role in these evolutionary divergences.
  • Comparative genomics has identified conserved non-coding regions with accelerated sequence changes in humans, termed non-coding human accelerated regions (ncHARs).

Purpose of the Study:

  • To identify and characterize regulatory sequences with potentially human-specific functions.
  • To investigate the role of ncHARs in human development and evolution.
  • To predict and validate developmental enhancers within ncHARs.

Main Methods:

  • Analysis of DNA sequence, evolutionary history, histone modifications, chromatin state, and transcription factor binding sites for 2649 ncHARs.
  • Prediction of developmental enhancer activity based on TF binding site gain/loss and gene expression patterns.
  • Functional testing of 29 ncHARs in transgenic mice to assess enhancer activity in embryonic tissues.

Main Results:

  • At least 30% of analyzed ncHARs were predicted to function as developmental enhancers.
  • 24 novel developmental enhancers were identified and active in both human and chimpanzee sequences in mouse embryos.
  • 17 enhancers showed consistent activity in specific embryonic tissues, with five exhibiting differential activity between human and chimpanzee sequences at embryonic day 11.5.

Conclusions:

  • ncHARs represent promising candidates for regulatory sequences with human-specific functions.
  • Changes in human non-coding DNA within these enhancers may underlie human-specific developmental patterns.
  • These findings contribute to understanding the genetic basis of unique human biology and evolution.