Experimental evolution of diverse Escherichia coli metabolic mutants identifies genetic loci for convergent adaptation of growth rate.
Cell growth is determined by substrate availability and the cell's metabolic capacity to assimilate substrates into building blocks. Metabolic genes that determine growth rate may interact synergistically or antagonistically, and can accelerate or slow growth, depending on genetic background an...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-03-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC5892946?pdf=render |
| _version_ | 1811336897886158848 |
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| author | Thomas P Wytock Aretha Fiebig Jonathan W Willett Julien Herrou Aleksandra Fergin Adilson E Motter Sean Crosson |
| author_facet | Thomas P Wytock Aretha Fiebig Jonathan W Willett Julien Herrou Aleksandra Fergin Adilson E Motter Sean Crosson |
| author_sort | Thomas P Wytock |
| collection | DOAJ |
| description | Cell growth is determined by substrate availability and the cell's metabolic capacity to assimilate substrates into building blocks. Metabolic genes that determine growth rate may interact synergistically or antagonistically, and can accelerate or slow growth, depending on genetic background and environmental conditions. We evolved a diverse set of Escherichia coli single-gene deletion mutants with a spectrum of growth rates and identified mutations that generally increase growth rate. Despite the metabolic differences between parent strains, mutations that enhanced growth largely mapped to core transcription machinery, including the β and β' subunits of RNA polymerase (RNAP) and the transcription elongation factor, NusA. The structural segments of RNAP that determine enhanced growth have been previously implicated in antibiotic resistance and in the control of transcription elongation and pausing. We further developed a computational framework to characterize how the transcriptional changes that occur upon acquisition of these mutations affect growth rate across strains. Our experimental and computational results provide evidence for cases in which RNAP mutations shift the competitive balance between active transcription and gene silencing. This study demonstrates that mutations in specific regions of RNAP are a convergent adaptive solution that can enhance the growth rate of cells from distinct metabolic states. |
| first_indexed | 2024-04-13T17:46:17Z |
| format | Article |
| id | doaj.art-9a61da60be5249d1a72d05049d1c145b |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-13T17:46:17Z |
| publishDate | 2018-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-9a61da60be5249d1a72d05049d1c145b2022-12-22T02:36:57ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042018-03-01143e100728410.1371/journal.pgen.1007284Experimental evolution of diverse Escherichia coli metabolic mutants identifies genetic loci for convergent adaptation of growth rate.Thomas P WytockAretha FiebigJonathan W WillettJulien HerrouAleksandra FerginAdilson E MotterSean CrossonCell growth is determined by substrate availability and the cell's metabolic capacity to assimilate substrates into building blocks. Metabolic genes that determine growth rate may interact synergistically or antagonistically, and can accelerate or slow growth, depending on genetic background and environmental conditions. We evolved a diverse set of Escherichia coli single-gene deletion mutants with a spectrum of growth rates and identified mutations that generally increase growth rate. Despite the metabolic differences between parent strains, mutations that enhanced growth largely mapped to core transcription machinery, including the β and β' subunits of RNA polymerase (RNAP) and the transcription elongation factor, NusA. The structural segments of RNAP that determine enhanced growth have been previously implicated in antibiotic resistance and in the control of transcription elongation and pausing. We further developed a computational framework to characterize how the transcriptional changes that occur upon acquisition of these mutations affect growth rate across strains. Our experimental and computational results provide evidence for cases in which RNAP mutations shift the competitive balance between active transcription and gene silencing. This study demonstrates that mutations in specific regions of RNAP are a convergent adaptive solution that can enhance the growth rate of cells from distinct metabolic states.http://europepmc.org/articles/PMC5892946?pdf=render |
| spellingShingle | Thomas P Wytock Aretha Fiebig Jonathan W Willett Julien Herrou Aleksandra Fergin Adilson E Motter Sean Crosson Experimental evolution of diverse Escherichia coli metabolic mutants identifies genetic loci for convergent adaptation of growth rate. PLoS Genetics |
| title | Experimental evolution of diverse Escherichia coli metabolic mutants identifies genetic loci for convergent adaptation of growth rate. |
| title_full | Experimental evolution of diverse Escherichia coli metabolic mutants identifies genetic loci for convergent adaptation of growth rate. |
| title_fullStr | Experimental evolution of diverse Escherichia coli metabolic mutants identifies genetic loci for convergent adaptation of growth rate. |
| title_full_unstemmed | Experimental evolution of diverse Escherichia coli metabolic mutants identifies genetic loci for convergent adaptation of growth rate. |
| title_short | Experimental evolution of diverse Escherichia coli metabolic mutants identifies genetic loci for convergent adaptation of growth rate. |
| title_sort | experimental evolution of diverse escherichia coli metabolic mutants identifies genetic loci for convergent adaptation of growth rate |
| url | http://europepmc.org/articles/PMC5892946?pdf=render |
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