cis versus trans effects
Jovelin R 2009 Rapid sequence evolution of transcription factors controlling neuron differentiation in Caenorhabditis. Mol Evol Biol 26:2373-2386.
- the role of transcription factor (TF) divergence in developmental evolution may be underestimated
- TFs are not as highly constrained as commonly thought
- the role of divergence in developmental regulatory genes during the evolution of gene regulatory networks requires further attention
- whether phenotypic evolution proceeds predominantly through changes in regulatory sequences or changes in protein sequences has ignited an intense debate
- with the argument in favor of the cis-regulatory hypothesis
- focusing on the prediction of strong conservation of TF function
- nonetheless, recent findings from cross-species gene-swapping experiments indicate that functional equivalence between distant TF orthologs is only partial or nonexistent
- a major assumption underlying arguments against a substantial role for TF sequence evolution is that mutations in the coding sequence of highly pleiotropic genes are likely to be deleterious and thus selected against
- this notion is supported by a negative correlation between nonsynonymous substitution rate and gene expression breadth
- Wagner and Lynch report that contrary to common belief, about a third of human TFs are tissue specific
- they also argue that the negative pleiotropic effect of mutations can be reduced by structural protein motifs and alternative splicing that make TFs highly modular
- the combinatorial mode of action of TFs can result in tissue-specific novel functions by establishing new interactions with cofactors or other TFs restricted to tissues in which all partners are expressed
