Dynamics of transcription factor binding site evolution Journal Article

Author(s): Tuğrul, Murat; Paixão, Tiago; Barton, Nicholas H; Tkačik, Gašper
Article Title: Dynamics of transcription factor binding site evolution
Affiliation IST Austria
Abstract: Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key regulatory mechanism that determines gene expression and hence heritable phenotypic variation. We use a biophysical model for directional selection on gene expression to estimate the rates of gain and loss of transcription factor binding sites (TFBS) in finite populations under both point and insertion/deletion mutations. Our results show that these rates are typically slow for a single TFBS in an isolated DNA region, unless the selection is extremely strong. These rates decrease drastically with increasing TFBS length or increasingly specific protein-DNA interactions, making the evolution of sites longer than ∼ 10 bp unlikely on typical eukaryotic speciation timescales. Similarly, evolution converges to the stationary distribution of binding sequences very slowly, making the equilibrium assumption questionable. The availability of longer regulatory sequences in which multiple binding sites can evolve simultaneously, the presence of “pre-sites” or partially decayed old sites in the initial sequence, and biophysical cooperativity between transcription factors, can all facilitate gain of TFBS and reconcile theoretical calculations with timescales inferred from comparative genomics.
Journal Title: PLoS Genetics
Volume: 11
Issue 11
ISSN: 1553-7404
Publisher: Public Library of Science  
Date Published: 2015-11-06
Start Page: Article number: e1005639
Copyright Statement: CC BY
Sponsor: This work was supported by the ERC Advanced Grant “Selection and Information”, ref 250152.
DOI: 10.1371/journal.pgen.1005639
Notes: We thank Magdalena Steinrück, Georg Rieckh, Ferran Palero and Ziya Kalay for helpful comments.
Open access: yes (OA journal)