cis versus trans effects

Graze RM, McIntyre LM, Main BJ, Wayne ML & Nuzhdin SV 2009 Regulatory divergence in Drosophila melanogaster and D. simulans, a genome-wide analysis of allele-specific expression. Genetics, in press.
doi:10.1534/genetics.109.105957

  • variation in cis and trans regulation may be shaped by different evolutionary forces
  • regulatory differences between species are a result of multiple cis and trans differences
  • and their interactions
  • the relative number of cis and trans effects have been studied in Drosophila at different levels of divergence and using different experimental designs
  • counts of cis and trans reported in eQTL and chromosome substitution experiments are not necessarily directly comparable to cis and trans as inferred from F1 hybrid based experiments
  • in a F1 hybrid design which infers cis and trans from comparisons of allele-specific expression, the inference of trans refers to the cumulative trans influences on expression of a single gene
  • the main effect is not separately estimable from the interactions
  • trans effects of potentially multiple genes are estimated as a whole, rather than individually
  • if trans acting regulatory divergence occurs in multiple genes, and the effects are compensatory such that the total level of expression remains relatively constant, then these trans effects will not be detected in the hybrid design
  • Cis effect estimates may also differ between approaches because the cis component in a hybrid experimental design can consist of both main effects and interactions, whereas eQTL designs can separate these terms to some degree
  • the contribution of genetic interactions to expression variation is expected to increase with divergence
  • however, a similar study of second chromosome substitutions, also in males found no increase in trans with increasing divergence (Lemos et al. 2008)
  • the relative contribution of divergence time within and between species remains unclear
  • deleterious regulatory interactions in otherwise functionally conserved genes may contribute to reproductive isolation between these species