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Effect of random and hub gene disruptions on environmental and mutational robustness in Escherichia coli.

Cooper TF, Morby AP, Gunn A, Schneider D - BMC Genomics (2006)

Bottom Line: We found that disruption of random genes had less effect on robustness to environmental stress than did the targeted disruption of hub genes.When we compared the effect of each disruption on environmental and mutational stress, we found a negative relationship, such that strains that were more environmentally robust tended to be less robust to mutational stress.That E. coli can reduce the effect of environmental stress without reducing the phenotypic effect of additional mutations, indicates that robustness and evolvability need not be antagonistic.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Biological Sciences, University of Auckland, Auckland, New Zealand. t.cooper@auckland.ac.nz

ABSTRACT

Background: Genome-wide profiling has allowed the regulatory interaction networks of many organisms to be visualised and the pattern of connections between genes to be studied. These networks are non-random, following a power-law distribution with a small number of well-connected 'hubs' and many genes with only one or a few connections. Theoretical work predicts that power-law networks display several unique properties. One of the most biologically interesting of these is an intrinsic robustness to disturbance such that removal of a random gene will have little effect on network function. Conversely, targeted removal of a hub gene is expected to have a large effect.

Results: We compared the response of Escherichia coli to environmental and mutational stress following disruption of random or hub genes. We found that disruption of random genes had less effect on robustness to environmental stress than did the targeted disruption of hub genes. In contrast, random disruption strains were slightly less robust to the effect of mutational stress than were hub disruption strains. When we compared the effect of each disruption on environmental and mutational stress, we found a negative relationship, such that strains that were more environmentally robust tended to be less robust to mutational stress.

Conclusion: Our results demonstrate that mutant strains of E. coli respond differently to stress, depending on whether random or hub genes are disrupted. This difference indicates that the power-law distribution of regulatory interactions has biological significance, making random disruptions less deleterious to organisms facing environmental stress. That E. coli can reduce the effect of environmental stress without reducing the phenotypic effect of additional mutations, indicates that robustness and evolvability need not be antagonistic.

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Relationship between environmental and mutational robustness. Because different environmental stresses had different mean effects on growth rate we normalized the effect of each stress to have a mean of zero. Therefore values on this axis above zero do not indicate that the effect of stress was positive. Average of median values plotted. Error bars indicate standard errors. Reference strain, hollow triangle; random disruption strains, solid circles; targeted hub disruption strains, hollow circles.
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Figure 4: Relationship between environmental and mutational robustness. Because different environmental stresses had different mean effects on growth rate we normalized the effect of each stress to have a mean of zero. Therefore values on this axis above zero do not indicate that the effect of stress was positive. Average of median values plotted. Error bars indicate standard errors. Reference strain, hollow triangle; random disruption strains, solid circles; targeted hub disruption strains, hollow circles.

Mentions: To assess the similarity in response to environmental and mutational stress, we compared the average effect of each stress type for each disruption strain (figure 4). If similar mechanisms underlie the effect of each stress type, we expected a positive correlation between environmental and mutational robustness. In fact, the correlation between the effect of the perturbations on growth rate was negative, though this relationship was not significant (Pearson, r = -0.413, P = 0.161). Visual inspection of the data indicated that this relationship may have been biased by an outlying point corresponding to the fis-deleted strain, which had much lower environmental robustness than any other disruption strain. When we repeated the analysis using a non-parametric test (Kendall, tau b = -0.359, P = 0.088), or omitting this strain (Pearson, r = -0.644, P = 0.032), the negative relationship between environmental and mutational robustness became much stronger. Together, these results indicate a tendency for more environmentally robust strains to be less mutationally robust.


Effect of random and hub gene disruptions on environmental and mutational robustness in Escherichia coli.

Cooper TF, Morby AP, Gunn A, Schneider D - BMC Genomics (2006)

Relationship between environmental and mutational robustness. Because different environmental stresses had different mean effects on growth rate we normalized the effect of each stress to have a mean of zero. Therefore values on this axis above zero do not indicate that the effect of stress was positive. Average of median values plotted. Error bars indicate standard errors. Reference strain, hollow triangle; random disruption strains, solid circles; targeted hub disruption strains, hollow circles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1590030&req=5

Figure 4: Relationship between environmental and mutational robustness. Because different environmental stresses had different mean effects on growth rate we normalized the effect of each stress to have a mean of zero. Therefore values on this axis above zero do not indicate that the effect of stress was positive. Average of median values plotted. Error bars indicate standard errors. Reference strain, hollow triangle; random disruption strains, solid circles; targeted hub disruption strains, hollow circles.
Mentions: To assess the similarity in response to environmental and mutational stress, we compared the average effect of each stress type for each disruption strain (figure 4). If similar mechanisms underlie the effect of each stress type, we expected a positive correlation between environmental and mutational robustness. In fact, the correlation between the effect of the perturbations on growth rate was negative, though this relationship was not significant (Pearson, r = -0.413, P = 0.161). Visual inspection of the data indicated that this relationship may have been biased by an outlying point corresponding to the fis-deleted strain, which had much lower environmental robustness than any other disruption strain. When we repeated the analysis using a non-parametric test (Kendall, tau b = -0.359, P = 0.088), or omitting this strain (Pearson, r = -0.644, P = 0.032), the negative relationship between environmental and mutational robustness became much stronger. Together, these results indicate a tendency for more environmentally robust strains to be less mutationally robust.

Bottom Line: We found that disruption of random genes had less effect on robustness to environmental stress than did the targeted disruption of hub genes.When we compared the effect of each disruption on environmental and mutational stress, we found a negative relationship, such that strains that were more environmentally robust tended to be less robust to mutational stress.That E. coli can reduce the effect of environmental stress without reducing the phenotypic effect of additional mutations, indicates that robustness and evolvability need not be antagonistic.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Biological Sciences, University of Auckland, Auckland, New Zealand. t.cooper@auckland.ac.nz

ABSTRACT

Background: Genome-wide profiling has allowed the regulatory interaction networks of many organisms to be visualised and the pattern of connections between genes to be studied. These networks are non-random, following a power-law distribution with a small number of well-connected 'hubs' and many genes with only one or a few connections. Theoretical work predicts that power-law networks display several unique properties. One of the most biologically interesting of these is an intrinsic robustness to disturbance such that removal of a random gene will have little effect on network function. Conversely, targeted removal of a hub gene is expected to have a large effect.

Results: We compared the response of Escherichia coli to environmental and mutational stress following disruption of random or hub genes. We found that disruption of random genes had less effect on robustness to environmental stress than did the targeted disruption of hub genes. In contrast, random disruption strains were slightly less robust to the effect of mutational stress than were hub disruption strains. When we compared the effect of each disruption on environmental and mutational stress, we found a negative relationship, such that strains that were more environmentally robust tended to be less robust to mutational stress.

Conclusion: Our results demonstrate that mutant strains of E. coli respond differently to stress, depending on whether random or hub genes are disrupted. This difference indicates that the power-law distribution of regulatory interactions has biological significance, making random disruptions less deleterious to organisms facing environmental stress. That E. coli can reduce the effect of environmental stress without reducing the phenotypic effect of additional mutations, indicates that robustness and evolvability need not be antagonistic.

Show MeSH
Related in: MedlinePlus