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AAV Deployment of Enhancer-Based Expression Constructs In Vivo in Mouse Brain
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Comment on "Human-specific gain of function in a developmental enhancer".

Laurent Duret1, Nicolas Galtier

  • 1Université de Lyon, Université Lyon 1, CNRS, UMR5558, Laboratoire de Biométrie et Biologie Evolutive, F-69622, Villeurbanne, France. duret@biomserv.univ-lyon1.fr

Science (New York, N.Y.)
|February 7, 2009
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Summary

The human-specific sequence HACNS1 shows neutral evolution, not positive selection. Its functional changes likely result from biased gene conversion, not adaptation.

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Area of Science:

  • Evolutionary biology
  • Human genetics
  • Molecular evolution

Background:

  • The conserved noncoding sequence HACNS1 was previously proposed to be under positive selection, driving human adaptation.
  • This hypothesis was based on observed substitution patterns in HACNS1.

Discussion:

  • This study re-evaluates the evolutionary patterns of HACNS1.
  • Substitution patterns in HACNS1 are more indicative of biased gene conversion (BGC), a neutral evolutionary process.
  • Deleterious mutations accumulating due to BGC may explain observed functional changes.

Key Insights:

  • HACNS1 evolution is better explained by neutral processes like BGC than positive selection.
  • The functional changes in HACNS1 are unlikely to be adaptations.
  • Biased gene conversion can lead to apparent functional shifts without adaptive pressure.

Outlook:

  • Further research is needed to fully understand the role of BGC in shaping conserved noncoding elements.
  • Re-evaluation of other putatively selected regions using BGC models is warranted.
  • This challenges previous interpretations of human adaptation based on specific genetic elements.