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Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution

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Title: Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution
Authors: Schaerli, Y
Jiménez, A
Duarte, JM
Mihajlovic, L
Renggli, J
Isalan, M
Sharpe, J
Wagner, A
Item Type: Journal Article
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.
Issue Date: 1-Sep-2018
Date of Acceptance: 15-Aug-2018
URI: http://hdl.handle.net/10044/1/63525
DOI: https://dx.doi.org/10.15252/msb.20178102
ISSN: 1744-4292
Publisher: European Molecular Biology Organization
Journal / Book Title: Molecular Systems Biology
Volume: 14
Copyright Statement: © 2018 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Wellcome Trust
Wellcome Trust
VolkwagenStiftung
Funder's Grant Number: 102944/Z/13/Z
102944/Z/13/Z
63062
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
constrained evolution
epistasis
gene regulatory networks
regulatory mechanisms
synthetic circuits
GREEN FLUORESCENT PROTEIN
ONE HUNDRED YEARS
DEVELOPMENTAL CONSTRAINTS
ESCHERICHIA-COLI
MORPHOLOGICAL EVOLUTION
TRANSCRIPTION CIRCUITS
LAC REPRESSOR
DEMAND THEORY
EVO-DEVO
EVOLVABILITY
constrained evolution
epistasis
gene regulatory networks
regulatory mechanisms
synthetic circuits
0699 Other Biological Sciences
Bioinformatics
Publication Status: Published
Article Number: e8102
Online Publication Date: 2018-09-10
Appears in Collections:Faculty of Natural Sciences



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