Abstract
Background: A central theme in (micro)biology is understanding the molecular basis of fitness i.e. which strategies are successful under which conditions; how do organisms implement such strategies at the molecular level; and which constraints shape the trade-offs between alternative strategies. Highly standardized microbial laboratory evolution experiments are ideally suited to approach these questions. For example, prolonged chemostats provide a constant environment in which the growth rate can be set, and the adaptive process of the organism to such environment can be subsequently characterized. Results: We performed parallel laboratory evolution of Lactococcus lactis in chemostats varying the quantitative value of the selective pressure by imposing two different growth rates. A mutation in one specific amino acid residue of the global transcriptional regulator of carbon metabolism, CcpA, was selected in all of the evolution experiments performed. We subsequently showed that this mutation confers predictable fitness improvements at other glucose-limited growth rates as well. In silico protein structural analysis of wild type and evolved CcpA, as well as biochemical and phenotypic assays, provided the underpinning molecular mechanisms that resulted in the specific reprogramming favored in constant environments. Conclusion: This study provides a comprehensive understanding of a case of microbial evolution and hints at the wide dynamic range that a single fitness-enhancing mutation may display. It demonstrates how the modulation of a pleiotropic regulator can be used by cells to improve one trait while simultaneously work around other limiting constraints, by fine-tuning the expression of a wide range of cellular processes.
| Original language | English |
|---|---|
| Article number | 15 |
| Pages (from-to) | 1-15 |
| Number of pages | 15 |
| Journal | BMC Evolutionary Biology |
| Volume | 19 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 10 Jan 2019 |
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Keywords
- Evolution
- Lactic acid bacteria
- Systems biology
Cite this
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Adaption to glucose limitation is modulated by the pleotropic regulator CcpA, independent of selection pressure strength. / Price, Claire E.; Branco Dos Santos, Filipe; Hesseling, Anne; Uusitalo, Jaakko J.; Bachmann, Herwig; Benavente, Vera; Goel, Anisha; Berkhout, Jan; Bruggeman, Frank J.; Marrink, Siewert Jan; Montalban-Lopez, Manolo; De Jong, Anne; Kok, Jan; Molenaar, Douwe; Poolman, Bert; Teusink, Bas; Kuipers, Oscar P.
In: BMC Evolutionary Biology, Vol. 19, No. 1, 15, 10.01.2019, p. 1-15.Research output: Contribution to Journal › Article › Academic › peer-review
TY - JOUR
T1 - Adaption to glucose limitation is modulated by the pleotropic regulator CcpA, independent of selection pressure strength
AU - Price, Claire E.
AU - Branco Dos Santos, Filipe
AU - Hesseling, Anne
AU - Uusitalo, Jaakko J.
AU - Bachmann, Herwig
AU - Benavente, Vera
AU - Goel, Anisha
AU - Berkhout, Jan
AU - Bruggeman, Frank J.
AU - Marrink, Siewert Jan
AU - Montalban-Lopez, Manolo
AU - De Jong, Anne
AU - Kok, Jan
AU - Molenaar, Douwe
AU - Poolman, Bert
AU - Teusink, Bas
AU - Kuipers, Oscar P.
PY - 2019/1/10
Y1 - 2019/1/10
N2 - Background: A central theme in (micro)biology is understanding the molecular basis of fitness i.e. which strategies are successful under which conditions; how do organisms implement such strategies at the molecular level; and which constraints shape the trade-offs between alternative strategies. Highly standardized microbial laboratory evolution experiments are ideally suited to approach these questions. For example, prolonged chemostats provide a constant environment in which the growth rate can be set, and the adaptive process of the organism to such environment can be subsequently characterized. Results: We performed parallel laboratory evolution of Lactococcus lactis in chemostats varying the quantitative value of the selective pressure by imposing two different growth rates. A mutation in one specific amino acid residue of the global transcriptional regulator of carbon metabolism, CcpA, was selected in all of the evolution experiments performed. We subsequently showed that this mutation confers predictable fitness improvements at other glucose-limited growth rates as well. In silico protein structural analysis of wild type and evolved CcpA, as well as biochemical and phenotypic assays, provided the underpinning molecular mechanisms that resulted in the specific reprogramming favored in constant environments. Conclusion: This study provides a comprehensive understanding of a case of microbial evolution and hints at the wide dynamic range that a single fitness-enhancing mutation may display. It demonstrates how the modulation of a pleiotropic regulator can be used by cells to improve one trait while simultaneously work around other limiting constraints, by fine-tuning the expression of a wide range of cellular processes.
AB - Background: A central theme in (micro)biology is understanding the molecular basis of fitness i.e. which strategies are successful under which conditions; how do organisms implement such strategies at the molecular level; and which constraints shape the trade-offs between alternative strategies. Highly standardized microbial laboratory evolution experiments are ideally suited to approach these questions. For example, prolonged chemostats provide a constant environment in which the growth rate can be set, and the adaptive process of the organism to such environment can be subsequently characterized. Results: We performed parallel laboratory evolution of Lactococcus lactis in chemostats varying the quantitative value of the selective pressure by imposing two different growth rates. A mutation in one specific amino acid residue of the global transcriptional regulator of carbon metabolism, CcpA, was selected in all of the evolution experiments performed. We subsequently showed that this mutation confers predictable fitness improvements at other glucose-limited growth rates as well. In silico protein structural analysis of wild type and evolved CcpA, as well as biochemical and phenotypic assays, provided the underpinning molecular mechanisms that resulted in the specific reprogramming favored in constant environments. Conclusion: This study provides a comprehensive understanding of a case of microbial evolution and hints at the wide dynamic range that a single fitness-enhancing mutation may display. It demonstrates how the modulation of a pleiotropic regulator can be used by cells to improve one trait while simultaneously work around other limiting constraints, by fine-tuning the expression of a wide range of cellular processes.
KW - Evolution
KW - Lactic acid bacteria
KW - Systems biology
UR - http://www.scopus.com/inward/record.url?scp=85059828875&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059828875&partnerID=8YFLogxK
U2 - 10.1186/s12862-018-1331-x
DO - 10.1186/s12862-018-1331-x
M3 - Article
VL - 19
SP - 1
EP - 15
JO - BMC Evolutionary Biology
JF - BMC Evolutionary Biology
SN - 1471-2148
IS - 1
M1 - 15
ER -