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- Title
Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution.
- Authors
Schaerli, Yolanda; Mihajlovic, Ljiljana; Duarte, José M.; Wagner, Andreas; Jiménez, Alba; Sharpe, James; Renggli, Julien; Isalan, Mark
- Abstract
Abstract: Phenotypic variation is the raw material of adaptive Darwinian evolution. The phenotypic variation found in organismal development is biased towards certain phenotypes, but the molecular mechanisms behind such biases are still poorly understood. Gene regulatory networks have been proposed as one cause of constrained phenotypic variation. However, most pertinent evidence is theoretical rather than experimental. Here, we study evolutionary biases in two synthetic gene regulatory circuits expressed in Escherichia coli that produce a gene expression stripe—a pivotal pattern in embryonic development. The two parental circuits produce the same phenotype, but create it through different regulatory mechanisms. We show that mutations cause distinct novel phenotypes in the two networks and use a combination of experimental measurements, mathematical modelling and DNA sequencing to understand why mutations bring forth only some but not other novel gene expression phenotypes. Our results reveal that the regulatory mechanisms of networks restrict the possible phenotypic variation upon mutation. Consequently, seemingly equivalent networks can indeed be distinct in how they constrain the outcome of further evolution.
- Subjects
CONSTRAINED optimization; EPISTASIS (Genetics); GENETIC regulation; GENE regulatory networks; REGULATOR genes; BIOLOGICAL circuits
- Publication
Molecular Systems Biology, 2018, Vol 14, Issue 9, p1
- ISSN
1744-4292
- Publication type
Article
- DOI
10.15252/msb.20178102