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DNA sequence insertion and evolutionary variation in gene regulation

R J Britten1

  • 1Division of Biology, California Institute of Technology, Corona del Mar 92625, USA.

Proceedings of the National Academy of Sciences of the United States of America
|September 3, 1996
PubMed
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Genomic insertions of DNA sequences, like mobile elements, can evolve to regulate gene expression. These ancient insertions, particularly Alu sequences in humans, significantly contribute to evolutionary regulatory variation.

Area of Science:

  • Genomics
  • Evolutionary Biology
  • Molecular Biology

Background:

  • Repetitive DNA and mobile elements are common in eukaryotic genomes.
  • The long-term evolutionary impact of these insertions on gene regulation is an area of active research.

Purpose of the Study:

  • To review current evidence on how past insertions of sequence elements into gene regions influence the regulation of gene expression.
  • To highlight examples where these inserted sequences have been preserved and modified by selection to control transcription.

Main Methods:

  • Review of published eukaryotic examples focusing on functional regulatory roles of ancient insertions.
  • Exclusion of cases where transcription initiation occurred within the insert but not regulatory control modification.
  • Categorization of examples including mammalian endogenous retroviruses, sea urchin repetitive sequences, and human Alu sequences.

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Main Results:

  • Ten eukaryotic examples demonstrate preserved and selected insertions (repetitive DNA, mobile elements) that now regulate adjacent gene transcription.
  • Two examples involve long terminal repeats of mammalian endogenous retroviruses.
  • Two examples show transcriptional control by sea urchin genome repetitive sequences.
  • Six examples illustrate ancient Alu sequence insertions in human genes that are now central to transcription control/enhancement.
  • The number of identified Alu-mediated gene control examples has tripled recently, indicating a growing trend.

Conclusions:

  • Insertion of sequence elements into genomes has historically been a significant driver of regulatory variation.
  • Ancient DNA insertions, once integrated, can be evolutionarily conserved and modified to play crucial roles in gene expression control.
  • The ongoing discovery of such examples, particularly with Alu sequences, underscores their importance in genome evolution.