Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution
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 a...
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| Format: | Article |
| Language: | English |
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Springer Nature
2018-09-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20178102 |
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| author | Yolanda Schaerli Alba Jiménez José M Duarte Ljiljana Mihajlovic Julien Renggli Mark Isalan James Sharpe Andreas Wagner |
| author_facet | Yolanda Schaerli Alba Jiménez José M Duarte Ljiljana Mihajlovic Julien Renggli Mark Isalan James Sharpe Andreas Wagner |
| author_sort | Yolanda Schaerli |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c164d92a7ca6416bbea3fd62ef8230e6 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2018-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-c164d92a7ca6416bbea3fd62ef8230e62025-08-20T03:43:31ZengSpringer NatureMolecular Systems Biology1744-42922018-09-0114911810.15252/msb.20178102Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolutionYolanda Schaerli0Alba Jiménez1José M Duarte2Ljiljana Mihajlovic3Julien Renggli4Mark Isalan5James Sharpe6Andreas Wagner7Department of Fundamental Microbiology, University of LausanneSystems Biology Program, Centre for Genomic Regulation (CRG), Universitat Pompeu FabraDepartment of Evolutionary Biology and Environmental Studies, University of ZurichDepartment of Fundamental Microbiology, University of LausanneIndependent ResearcherDepartment of Life Sciences, Imperial College LondonSystems Biology Program, Centre for Genomic Regulation (CRG), Universitat Pompeu FabraDepartment of Evolutionary Biology and Environmental Studies, University of ZurichAbstract 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.https://doi.org/10.15252/msb.20178102constrained evolutionepistasisgene regulatory networksregulatory mechanismssynthetic circuits |
| spellingShingle | Yolanda Schaerli Alba Jiménez José M Duarte Ljiljana Mihajlovic Julien Renggli Mark Isalan James Sharpe Andreas Wagner Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution Molecular Systems Biology constrained evolution epistasis gene regulatory networks regulatory mechanisms synthetic circuits |
| title | Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution |
| title_full | Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution |
| title_fullStr | Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution |
| title_full_unstemmed | Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution |
| title_short | Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution |
| title_sort | synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution |
| topic | constrained evolution epistasis gene regulatory networks regulatory mechanisms synthetic circuits |
| url | https://doi.org/10.15252/msb.20178102 |
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