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Evidence for stabilizing selection in a eukaryotic enhancer element

Author

Listed:
  • Michael Z. Ludwig

    (University of Chicago)

  • Casey Bergman

    (University of Chicago)

  • Nipam H. Patel

    (MC1028, N-101)

  • Martin Kreitman

    (University of Chicago)

Abstract

Eukaryotic gene expression is mediated by compact cis-regulatory modules, or enhancers, which are bound by specific sets of transcription factors1. The combinatorial interaction of these bound transcription factors determines time- and tissue-specific gene activation or repression. The even-skipped stripe 2 element controls the expression of the second transverse stripe of even-skipped messenger RNA in Drosophila melanogaster embryos, and is one of the best characterized eukaryotic enhancers2,3,4. Although even-skipped stripe 2 expression is strongly conserved in Drosophila, the stripe 2 element itself has undergone considerable evolutionary change in its binding-site sequences and the spacing between them. We have investigated this apparent contradiction, and here we show that two chimaeric enhancers, constructed by swapping the 5′ and 3′ halves of the native stripe 2 elements of two species, no longer drive expression of a reporter gene in the wild-type pattern. Sequence differences between species have functional consequences, therefore, but they are masked by other co-evolved differences. On the basis of these results, we present a model for the evolution of eukaryotic regulatory sequences.

Suggested Citation

  • Michael Z. Ludwig & Casey Bergman & Nipam H. Patel & Martin Kreitman, 2000. "Evidence for stabilizing selection in a eukaryotic enhancer element," Nature, Nature, vol. 403(6769), pages 564-567, February.
  • Handle: RePEc:nat:nature:v:403:y:2000:i:6769:d:10.1038_35000615
    DOI: 10.1038/35000615
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    Cited by:

    1. Pradipta Ray & Suyash Shringarpure & Mladen Kolar & Eric P Xing, 2008. "CSMET: Comparative Genomic Motif Detection via Multi-Resolution Phylogenetic Shadowing," PLOS Computational Biology, Public Library of Science, vol. 4(6), pages 1-20, June.
    2. Lauren A. Choate & Gilad Barshad & Pierce W. McMahon & Iskander Said & Edward J. Rice & Paul R. Munn & James J. Lewis & Charles G. Danko, 2021. "Multiple stages of evolutionary change in anthrax toxin receptor expression in humans," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    3. Armita Nourmohammad & Michael Lässig, 2011. "Formation of Regulatory Modules by Local Sequence Duplication," PLOS Computational Biology, Public Library of Science, vol. 7(10), pages 1-12, October.
    4. Iksoo Huh & Isabel Mendizabal & Taesung Park & Soojin V Yi, 2018. "Functional conservation of sequence determinants at rapidly evolving regulatory regions across mammals," PLOS Computational Biology, Public Library of Science, vol. 14(10), pages 1-21, October.
    5. Mathilde Paris & Tommy Kaplan & Xiao Yong Li & Jacqueline E Villalta & Susan E Lott & Michael B Eisen, 2013. "Extensive Divergence of Transcription Factor Binding in Drosophila Embryos with Highly Conserved Gene Expression," PLOS Genetics, Public Library of Science, vol. 9(9), pages 1-18, September.

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