Abstract
BackgroundChanges in gene regulatory networks drive the evolution of phenotypic diversity both within and between species. Rewiring of transcriptional networks is achieved either by changes to transcription factor binding sites or by changes to the physical interactions among transcription factor proteins. It has been suggested that the evolution of cooperative binding among factors can facilitate the adaptive rewiring of a regulatory network.ResultsWe use a population-genetic model to explore when cooperative binding of transcription factors is favored by evolution, and what effects cooperativity then has on the adaptive re-writing of regulatory networks. We consider a pair of transcription factors that regulate multiple targets and overlap in the sets of target genes they regulate. We show that, under stabilising selection, cooperative binding between the transcription factors is favoured provided the amount of overlap between their target genes exceeds a threshold. The value of this threshold depends on several population-genetic factors: strength of selection on binding sites, cost of pleiotropy associated with protein-protein interactions, rates of mutation and population size. Once it is established, we find that cooperative binding of transcription factors significantly accelerates the adaptive rewiring of transcriptional networks under positive selection. We compare our qualitative predictions to systematic data on Saccharomyces cerevisiae transcription factors, their binding sites, and their protein-protein interactions.ConclusionsOur study reveals a rich set of evolutionary dynamics driven by a tradeoff between the beneficial effects of cooperative binding at targets shared by a pair of factors, and the detrimental effects of cooperative binding for non-shared targets. We find that cooperative regulation will evolve when transcription factors share a sufficient proportion of their target genes. These findings help to explain empirical pattens in datasets of transcription factors in Saccharomyces cerevisiae and, they suggest that changes to physical interactions between transcription factors can play a critical role in the evolution of gene regulatory networks.
Highlights
Changes in gene regulatory networks drive the evolution of phenotypic diversity both within and between species
Given the potential adaptive benefit of cooperative regulation, it makes sense to ask, when will cooperative binding between a pair of transcription factors be able to invade a population that lacks such cooperativity? To answer this we must understand the following tradeoff: cooperative binding between a pair of factors may result in improved regulation at the target genes shared by both factors, any mutation that results in a physical interaction between the transcription factors will effect all of their targets (Figure 1)
We have shown that cooperative binding between a pair of transcription factors is favoured under stabilising selection, provided the overlap between their targets is sufficiently large
Summary
Changes in gene regulatory networks drive the evolution of phenotypic diversity both within and between species. If selection favours a change in the way a group of genes are regulated, each of the target genes must independently gain novel binding sites and/or lose existing ones [8,9,11,12]. This has led to the proposal that adaptive rewiring of a regulatory network can be accelerated if pairs of transcription factors bind their targets cooperatively, through a physical interaction between the transcription factor proteins themselves [8,9,11]. The advantageous fitness effects of improved binding at some, shared targets must outweigh any deleterious effects of misregulation at other, non-shared targets in order for cooperative binding to be favored by evolution.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
