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Accelerated evolution of conserved noncoding sequences in humans.

Shyam Prabhakar1, James P Noonan, Svante Pääbo

  • 1U.S. Department of Energy (DOE) Joint Genome Institute, Walnut Creek, CA 94598, USA.

Science (New York, N.Y.)
|November 4, 2006
PubMed
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Human evolution involved significant changes in gene regulation, particularly in noncoding DNA sequences. These regulatory changes may explain unique human brain development and function.

Area of Science:

  • Evolutionary biology
  • Genomics
  • Neuroscience

Background:

  • Phenotypic divergence between humans and other mammals is linked to gene regulation changes.
  • The role of adaptive substitution in human regulatory sequences is not well understood.

Purpose of the Study:

  • To investigate the extent of adaptive substitution in human regulatory sequences.
  • To identify conserved noncoding sequences (CNSs) with human-specific substitutions.
  • To compare human noncoding evolution with that of chimpanzee and mouse.

Main Methods:

  • Identification of 992 conserved noncoding sequences (CNSs) with significant human-specific substitutions.
  • Analysis of accelerated CNSs near genes involved in neuronal cell adhesion.
  • Comparative analysis of accelerated CNSs in chimpanzee and mouse.

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Main Results:

  • A significant excess of human-specific substitutions was found in 992 CNSs.
  • These accelerated elements were disproportionately located near genes related to neuronal cell adhesion.
  • Chimpanzee accelerated CNSs showed enrichment near neuronal adhesion genes but little overlap with human CNSs, indicating independent evolution.
  • Mouse accelerated CNSs did not show a bias toward neuronal cell adhesion genes.

Conclusions:

  • Widespread cis-regulatory changes in human evolution likely contributed to unique human brain development and function.
  • Human and chimpanzee noncoding evolution shows independent trajectories toward distinct neuronal phenotypes.