Sepsid even-skipped enhancers are functionally conserved in Drosophila despite lack of sequence conservation

PLoS Genet. 2008 Jun 27;4(6):e1000106. doi: 10.1371/journal.pgen.1000106.

Abstract

The gene expression pattern specified by an animal regulatory sequence is generally viewed as arising from the particular arrangement of transcription factor binding sites it contains. However, we demonstrate here that regulatory sequences whose binding sites have been almost completely rearranged can still produce identical outputs. We sequenced the even-skipped locus from six species of scavenger flies (Sepsidae) that are highly diverged from the model species Drosophila melanogaster, but share its basic patterns of developmental gene expression. Although there is little sequence similarity between the sepsid eve enhancers and their well-characterized D. melanogaster counterparts, the sepsid and Drosophila enhancers drive nearly identical expression patterns in transgenic D. melanogaster embryos. We conclude that the molecular machinery that connects regulatory sequences to the transcription apparatus is more flexible than previously appreciated. In exploring this diverse collection of sequences to identify the shared features that account for their similar functions, we found a small number of short (20-30 bp) sequences nearly perfectly conserved among the species. These highly conserved sequences are strongly enriched for pairs of overlapping or adjacent binding sites. Together, these observations suggest that the local arrangement of binding sites relative to each other is more important than their overall arrangement into larger units of cis-regulatory function.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified / classification
  • Animals, Genetically Modified / embryology
  • Animals, Genetically Modified / genetics
  • Animals, Genetically Modified / metabolism
  • Base Sequence
  • Binding Sites
  • Conserved Sequence
  • Diptera / classification
  • Diptera / genetics*
  • Diptera / metabolism
  • Drosophila / classification
  • Drosophila / embryology
  • Drosophila / genetics*
  • Drosophila / metabolism
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Embryo, Nonmammalian / metabolism
  • Enhancer Elements, Genetic*
  • Evolution, Molecular*
  • Gene Expression Regulation, Developmental
  • Genome, Insect
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Insect Proteins / genetics*
  • Insect Proteins / metabolism
  • Sequence Alignment
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Drosophila Proteins
  • Homeodomain Proteins
  • Insect Proteins
  • Transcription Factors
  • eve protein, Drosophila