Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution.

Détails

Ressource 1Télécharger: Schaerli_MolSystBiol2018.pdf (755.77 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_E4CEE618A944
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution.
Périodique
Molecular systems biology
Auteur⸱e⸱s
Schaerli Y., Jiménez A., Duarte J.M., Mihajlovic L., Renggli J., Isalan M., Sharpe J., Wagner A.
ISSN
1744-4292 (Electronic)
ISSN-L
1744-4292
Statut éditorial
Publié
Date de publication
10/09/2018
Peer-reviewed
Oui
Volume
14
Numéro
9
Pages
e8102
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
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.
Mots-clé
Arabinose/metabolism, Arabinose/pharmacology, Biological Evolution, Cloning, Molecular, Culture Media/chemistry, Culture Media/pharmacology, Escherichia coli/drug effects, Escherichia coli/genetics, Escherichia coli/metabolism, Gene Expression Regulation, Gene Regulatory Networks, Genetic Variation, Genotype, Models, Genetic, Mutation, Phenotype, Selection, Genetic, Synthetic Biology/methods, constrained evolution, epistasis, gene regulatory networks, regulatory mechanisms, synthetic circuits
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/09/2018 13:01
Dernière modification de la notice
09/01/2020 7:10
Données d'usage