Functional evolution of a cis-regulatory module

PLoS Biol. 2005 Apr;3(4):e93. doi: 10.1371/journal.pbio.0030093. Epub 2005 Mar 15.


Lack of knowledge about how regulatory regions evolve in relation to their structure-function may limit the utility of comparative sequence analysis in deciphering cis-regulatory sequences. To address this we applied reverse genetics to carry out a functional genetic complementation analysis of a eukaryotic cis-regulatory module-the even-skipped stripe 2 enhancer-from four Drosophila species. The evolution of this enhancer is non-clock-like, with important functional differences between closely related species and functional convergence between distantly related species. Functional divergence is attributable to differences in activation levels rather than spatiotemporal control of gene expression. Our findings have implications for understanding enhancer structure-function, mechanisms of speciation and computational identification of regulatory modules.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Drosophila / classification
  • Drosophila / genetics*
  • Drosophila Proteins / genetics
  • Drosophila melanogaster / genetics*
  • Enhancer Elements, Genetic
  • Evolution, Molecular*
  • Gene Deletion
  • Gene Expression Regulation
  • Genetic Complementation Test
  • Homeodomain Proteins / genetics
  • Molecular Sequence Data
  • Peptide Fragments / genetics
  • Transcription Factors / genetics


  • Drosophila Proteins
  • Homeodomain Proteins
  • Peptide Fragments
  • Transcription Factors
  • eve protein, Drosophila

Associated data

  • GENBANK/AE003831
  • GENBANK/AF042709
  • GENBANK/AF042710
  • GENBANK/AF042711
  • GENBANK/AF042712
  • GENBANK/AY190939
  • GENBANK/AY190942