||Evolutionary Potential of Cis-Regulatory Mutations to Cause Rapid Changes in Transcription Factor Binding.
||Kurafeiski JD, Pinto P, Bornberg-Bauer E.
||Genome Biol Evol. (2019) 11(2): 406-414
Transcriptional regulation is crucial for all biological processes and well investigated at the molecular level for a wide range of
organisms. However, it is quite unclear how innovations, such as the activity of a novel regulatory element, evolve. In the case of
transcription factor (TF) binding, both a novel TF and a novel-binding site would need to evolve concertedly. Since promiscuous
functions have recently been identified as important intermediate steps in creating novel specific functions in many areas such as
enzyme evolution and protein–protein interactions,we ask here howpromiscuous binding of TFs to TF-binding sites (TFBSs) affects
the robustness and evolvability of this tightly regulated system. Specifically, we investigate the binding behavior of several hundred
TFs fromdifferent species at unprecedented breadth. Our results illustrate multiple aspects of TF-binding interactions, ranging from
correlations between the strength of the interaction bond and specificity, to preferences regarding TFBS nucleotide composition in
relation to both domains and binding specificity.We identified a subset of high A/T binding motifs.Motifs in this subset had many
functionally neutral one-error mutants, andwere bound by multiple different binding domains. Our results indicate that, especially
for some TF–TFBS associations, low binding specificity confers high degrees of evolvability, that is that fewmutations facilitate rapid
changes in transcriptional regulation, in particular for large and old TF families. In this study we identify binding motifs exhibiting
behavior indicating high evolutionary potential for innovations in transcriptional regulation.
Key words: transcriptional regulation, evolution of regulatory networks, binding specificity, neutral networks,
/Presenter : Jooseong Oh
/PMID : 30597011
/Date : 2019.04.18