An incoherent feedforward loop facilitates adaptive tuning of gene expression

Jungeui Hong, Nathan Brandt, Farah Abdul-Rahman, Ally Yang, Tim Hughes, David Gresham

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere32323
JournaleLife
Volume7
DOIs
StatePublished - Apr 5 2018

Fingerprint

Gene expression
Tuning
Ammonium Compounds
Gene Expression
Genes
Chemostats
Gene Regulatory Networks
DNA
Consensus Sequence
Missense Mutation
Regulator Genes
Yeast
Saccharomyces cerevisiae
Transcription Factors
Modulation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

An incoherent feedforward loop facilitates adaptive tuning of gene expression. / Hong, Jungeui; Brandt, Nathan; Abdul-Rahman, Farah; Yang, Ally; Hughes, Tim; Gresham, David.

In: eLife, Vol. 7, e32323, 05.04.2018.

Research output: Contribution to journalArticle

Hong, Jungeui ; Brandt, Nathan ; Abdul-Rahman, Farah ; Yang, Ally ; Hughes, Tim ; Gresham, David. / An incoherent feedforward loop facilitates adaptive tuning of gene expression. In: eLife. 2018 ; Vol. 7.
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