Regulatory changes underlying expression differences within and between Drosophila species

Nat Genet. 2008 Mar;40(3):346-50. doi: 10.1038/ng.77. Epub 2008 Feb 17.


Differences in gene expression are an important source of phenotypic variation, and can be caused by changes in cis and/or trans regulation. cis-regulatory variants alter allele-specific expression, whereas trans-regulatory variants influence expression of both alleles in a diploid cell. Because of this difference, we hypothesize that natural selection may favor one type of change over the other. Here, we investigate contributions of cis- and trans-regulatory changes to variable intra- and interspecific gene expression using four strains of Drosophila melanogaster, three strains of D. simulans and a total of 78 genes. We show that cis-regulatory changes account for a greater proportion of the expression differences observed between rather than within species. These data are inconsistent with a neutral model assuming equal probabilities of fixation for cis- and trans-regulatory polymorphisms, suggesting that natural selection influences the molecular mechanisms underlying divergent gene expression. Specifically, cis-regulatory changes seem to accumulate preferentially over time.

Publication types

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

MeSH terms

  • Animals
  • Crosses, Genetic
  • Drosophila / genetics*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Genes, Insect
  • Male
  • Regulatory Sequences, Nucleic Acid / physiology
  • Transcription Factors / physiology


  • Transcription Factors