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Transhydrogenase Promotes the Robustness and Evolvability of Deficient in NADPH Production


The structure of biological networks, like traffic systems or the Internet, features few hubs connected by numerous components. Though the conservation and high connectivity of hubs serve as key junctions to promote network expansion, addition or removal of connections surrounding hubs may disturb the whole system through their global linkage. How do biological networks mitigate hub perturbations during evolution? Using metabolism as an example, we studied the physiological and evolutionary consequences of genetically perturbed production of a hub metabolite NADPH in E. coli. We found that the expression of mTH, a phylogenetically conserved enzyme, was immediately upregulated and essential to counteract the hub perturbation. Moreover, long-term evolution of this pathway-modified E. coli in glucose growth media recurrently selected for mTH-upregulating mutations to restore the NADPH balance in all twelve replicate populations, regardless of several alternative solutions suggested in the literature. Corroborated by similar findings from laboratory evolution of a highly diverged species M. extorquens, our study suggests that mechanisms dedicated to mitigating hub perturbations promote both the robustness and evolvability of biological networks.


Vyšlo v časopise: Transhydrogenase Promotes the Robustness and Evolvability of Deficient in NADPH Production. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1005007
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005007

Souhrn

The structure of biological networks, like traffic systems or the Internet, features few hubs connected by numerous components. Though the conservation and high connectivity of hubs serve as key junctions to promote network expansion, addition or removal of connections surrounding hubs may disturb the whole system through their global linkage. How do biological networks mitigate hub perturbations during evolution? Using metabolism as an example, we studied the physiological and evolutionary consequences of genetically perturbed production of a hub metabolite NADPH in E. coli. We found that the expression of mTH, a phylogenetically conserved enzyme, was immediately upregulated and essential to counteract the hub perturbation. Moreover, long-term evolution of this pathway-modified E. coli in glucose growth media recurrently selected for mTH-upregulating mutations to restore the NADPH balance in all twelve replicate populations, regardless of several alternative solutions suggested in the literature. Corroborated by similar findings from laboratory evolution of a highly diverged species M. extorquens, our study suggests that mechanisms dedicated to mitigating hub perturbations promote both the robustness and evolvability of biological networks.


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