cis versus trans effects

Wittkopp PJ, Haerum BK & Clark AG 2004 Evolutionary changes in cis and trans gene regulation. Nature 430:85-88.

  • the distribution of cis- and trans-regulatory changes provides insight into the evolution of regulatory networks
  • these networks are composed of two classes of gene:
  • regulatory (for example those encoding transcription factors or signalling molecules)
  • structural (for example those encoding enzymes or cellular components)
  • regulatory genes (Fig. 4, filled circles) comprise internal connections in the network
  • changes in their expression often have trans-acting effects on the expression of many other genes
  • structural genes (Fig. 4, open circles) typically lie at terminal nodes of the network
  • changes in their expression have more limited effects on expression of other genes
  • our data set contains primarily structural genes
  • analysis of structural genes provides a complete view of the regulatory network
  • gene-specific changes at terminal nodes in the network detected as cis-regulatory changes
  • genetic changes located in upstream regulatory genes identifiable as trans-regulatory differences
  • a few cis-regulatory changes affecting regulatory genes could have widespread trans-acting effects on the expression of many downstream genes (Fig. 4a)
  • each structural gene's expression could be altered by its own cis-acting genetic changes (Fig. 4b)
  • interspecific expression differences were almost always caused, at least in part, by cis-regulatory changes in structural genes
  • differences in trans-regulation also affected half of the genes (Fig. 4c)
  • the prevalence of cis-regulatory changes suggests that differences in gene expression between D. melanogaster and D. simulans could have evolved by changing the expression of structural genes one gene at a time
  • regulatory differences observed in extant flies might not have been the original source of expression divergence
  • the genetic basis of variable gene expression is beginning to be elucidated
  • distinguishing between cis- and trans-regulatory changes is the first step in this process
  • it provides a crucial foothold for identifying the specific nucleotide changes underlying gene expression differences