cis versus trans effects

Fraser HB, Babak T, Tsang J, Zhou Y, Zhang B, Mehrabian M & Schadt EE 2011 Systematic detection of polygenic cis-regulatory evolution. PLoS Genet 7:e1002023.

  • the independence of eQTLs for different genes is critical for this test, since a single eQTL that affected many genes could lead to a strong bias in the directionality of effect even in the absence of lineage-specific selection
  • to ensure that each eQTL is independent, we considered only local eQTLs
  • that is, eQTLs located at genetic markers that are close in the genome to the gene whose expression they control
  • these local eQTLs have been shown to be primarily cis-acting
  • so we refer to these as cis-eQTL for brevity
  • we note that our test of selection is equally valid for local trans-acting eQTLs
  • since a single cis-eQTL could conceivably control multiple nearby genes, and thus violate the requirement for independence, we also discard genes that are located close to others in the same gene set
  • our microarrays cannot provide direct evidence of cis-regulation
  • since local eQTLs can occasionally be trans-acting
  • we cannot be confident that our results truly reflect selection solely on cis-acting elements
  • this study did not distinguish between adaptive versus non-adaptive change, or cis versus trans regulation, or tissue-specific versus non-specific expression changes, so the relevance to theories of tissue-specific adaptive cis-regulatory evolution is not clear
  • although most of the genes in our most significant gene sets are broadly expressed (not shown), their expression in all three tissues was affected by the recent selection on cis-regulation we detected