Dataset Information

An incoherent feedforward loop facilitates adaptive tuning of gene expression.

ABSTRACT: We studied adaptive evolution of gene expression using long-term experimental evolution of Saccharomyces cerevisiae in ammonium-limited chemostats. We found repeated selection for non-synonymous variation in the DNA binding domain of the transcriptional activator, GAT1, which functions with the repressor, DAL80 in an incoherent type-1 feedforward loop (I1-FFL) to control expression of the high affinity ammonium transporter gene, MEP2. Missense mutations in the DNA binding domain of GAT1 reduce its binding to the GATAA consensus sequence. However, we show experimentally, and using mathematical modeling, that decreases in GAT1 binding result in increased expression of MEP2 as a consequence of properties of I1-FFLs. Our results show that I1-FFLs, one of the most commonly occurring network motifs in transcriptional networks, can facilitate adaptive tuning of gene expression through modulation of transcription factor binding affinities. Our findings highlight the importance of gene regulatory architectures in the evolution of gene expression.

SUBMITTER: Hong J

PROVIDER: S-EPMC5903863 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An incoherent feedforward loop facilitates adaptive tuning of gene expression.

Hong Jungeui J Brandt Nathan N Abdul-Rahman Farah F Yang Ally A Hughes Tim T Gresham David D

eLife 20180405

We studied adaptive evolution of gene expression using long-term experimental evolution of <i>Saccharomyces cerevisiae</i> in ammonium-limited chemostats. We found repeated selection for non-synonymous variation in the DNA binding domain of the transcriptional activator, GAT1, which functions with the repressor, DAL80 in an incoherent type-1 feedforward loop (I1-FFL) to control expression of the high affinity ammonium transporter gene, MEP2. Missense mutations in the DNA binding domain of GAT1 r ...[more]

PMID: 29620523

Similar Datasets

Project description:BackgroundRegulation of gene expression is of paramount importance in all living systems. In the past two decades, it has been discovered that certain motifs, such as the feedforward motif, are overrepresented in gene regulatory circuits. Feedforward loops are also ubiquitous in process control engineering, and are nearly always structured so that one branch has the opposite effect of the other, which is a structure known as an "incoherent" feedforward loop in biology. In engineered systems, feedforward control loops are subject to several engineering constraints, including that (1) they are finely-tuned so that the system returns to the original steady state after a disturbance occurs (perfect adaptation), (2) they are typically only implemented in the combination with negative feedback, and (3) they can greatly improve the stability and dynamical characteristics of the conjoined negative feedback loop. On the other hand, in biology, incoherent feedforward loops can serve many purposes, one of which may be perfect adaptation. It is an open question as to whether those that achieve perfect adaptation are subject to the above engineering principles.ResultsWe analyzed an incoherent feedforward gene regulatory motif from the standpoint of the above engineering principles. In particular, we showed that an incoherent feedforward loop Type 1 (I1-FFL), from within a gene regulatory circuit, can be finely-tuned for perfect adaptation after a stimulus, and that the robustness of this behavior is increased by the presence of moderate negative feedback. In addition, we analyzed the advantages of adding a feedforward loop to a system that already operated under negative feedback, and found that the dynamical properties of the combined feedforward/feedback system were superior.ConclusionsOur analysis shows that many of the engineering principles used in engineering design of feedforward control are also applicable to feedforward loops in biological systems. We speculate that principles found in other domains of engineering may also be applicable to analogous structures in biology.

Dataset Information

An incoherent feedforward loop facilitates adaptive tuning of gene expression.

Publications

An incoherent feedforward loop facilitates adaptive tuning of gene expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets