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Metabolic erosion primarily through mutation accumulation, and not tradeoffs, drives limited evolution of substrate specificity in Escherichia coli.

Leiby N, Marx CJ - PLoS Biol. (2014)

Bottom Line: These reductions in growth by mutator strains were ameliorated by growth at lower temperature, consistent with the hypothesis that this metabolic erosion is largely caused by destabilizing mutations to the associated enzymes.To our surprise, we found no significant relationship between decreases in growth and dissimilarity to glucose metabolism.Taken as a whole, these data suggest that in a single resource environment, specialization does not mainly result as an inevitable consequence of adaptive tradeoffs, but rather due to the gradual accumulation of disabling mutations in unused portions of the genome.

View Article: PubMed Central - PubMed

Affiliation: Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, United States of America ; Systems Biology Graduate Program, Harvard University, Cambridge, Massachusetts, United States of America.

ABSTRACT
Evolutionary adaptation to a constant environment is often accompanied by specialization and a reduction of fitness in other environments. We assayed the ability of the Lenski Escherichia coli populations to grow on a range of carbon sources after 50,000 generations of adaptation on glucose. Using direct measurements of growth rates, we demonstrated that declines in performance were much less widespread than suggested by previous results from Biolog assays of cellular respiration. Surprisingly, there were many performance increases on a variety of substrates. In addition to the now famous example of citrate, we observed several other novel gains of function for organic acids that the ancestral strain only marginally utilized. Quantitative growth data also showed that strains with a higher mutation rate exhibited significantly more declines, suggesting that most metabolic erosion was driven by mutation accumulation and not by physiological tradeoffs. These reductions in growth by mutator strains were ameliorated by growth at lower temperature, consistent with the hypothesis that this metabolic erosion is largely caused by destabilizing mutations to the associated enzymes. We further hypothesized that reductions in growth rate would be greatest for substrates used most differently from glucose, and we used flux balance analysis to formulate this question quantitatively. To our surprise, we found no significant relationship between decreases in growth and dissimilarity to glucose metabolism. Taken as a whole, these data suggest that in a single resource environment, specialization does not mainly result as an inevitable consequence of adaptive tradeoffs, but rather due to the gradual accumulation of disabling mutations in unused portions of the genome.

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Substrate dissimilarity does not predict metabolic erosion.(A) A simple categorization of substrates as sugars and nonsugars finds that the correlation between relatedness to glucose and evolved metabolic changes is the opposite from what is hypothesized. (B) The FBA-predicted mutational target size does not correlate with decreases in growth rate. (C) Hamming distance between FBA-generated flux vectors for carbon sources partially predicts ancestral growth rate. Black dots indicate the growth rate of the two ancestral strains. A total of 268 reactions were predicted as necessary for optimal metabolism on glucose. (D) Hamming distance between a substrate and glucose does not correlate with increases or decreases in growth rate. The y axis is the log of the ratio of growth rate relative to the ancestor, with all ratios greater or less than e2 binned at the axis limit. For (C–D), purple dots are mutator strains, and orange dots are nonmutators. Larger dots at the axis extrema indicate more overlapping points, and the shading between purple and orange indicates the different proportions of mutators and nonmutators at that limit. For (B–D), substrates with the same x axis values were plotted with a slight offset, and the true value is listed in the axis label.
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pbio-1001789-g003: Substrate dissimilarity does not predict metabolic erosion.(A) A simple categorization of substrates as sugars and nonsugars finds that the correlation between relatedness to glucose and evolved metabolic changes is the opposite from what is hypothesized. (B) The FBA-predicted mutational target size does not correlate with decreases in growth rate. (C) Hamming distance between FBA-generated flux vectors for carbon sources partially predicts ancestral growth rate. Black dots indicate the growth rate of the two ancestral strains. A total of 268 reactions were predicted as necessary for optimal metabolism on glucose. (D) Hamming distance between a substrate and glucose does not correlate with increases or decreases in growth rate. The y axis is the log of the ratio of growth rate relative to the ancestor, with all ratios greater or less than e2 binned at the axis limit. For (C–D), purple dots are mutator strains, and orange dots are nonmutators. Larger dots at the axis extrema indicate more overlapping points, and the shading between purple and orange indicates the different proportions of mutators and nonmutators at that limit. For (B–D), substrates with the same x axis values were plotted with a slight offset, and the true value is listed in the axis label.

Mentions: We first tested whether evolved decreases in growth rate scaled with mutational target size. There is no expected behavior under this hypothesis for increases in growth rate, so we limited our analysis to combinations of strains and substrates for which growth rate had decreased. By identifying the reactions necessary for optimal growth on alternative substrates that are not necessary for growth on glucose, and determining the number of coding nucleotides necessary for those reactions, we were able to approximate the number of available mutations that would decrease growth rate on a substrate. Contrary to our hypothesis, we found no significant relationship between mutational target size and reduction in growth rate [p = 0.15, linear regression F test(1, 146) = 2.1] (Figure 3B).


Metabolic erosion primarily through mutation accumulation, and not tradeoffs, drives limited evolution of substrate specificity in Escherichia coli.

Leiby N, Marx CJ - PLoS Biol. (2014)

Substrate dissimilarity does not predict metabolic erosion.(A) A simple categorization of substrates as sugars and nonsugars finds that the correlation between relatedness to glucose and evolved metabolic changes is the opposite from what is hypothesized. (B) The FBA-predicted mutational target size does not correlate with decreases in growth rate. (C) Hamming distance between FBA-generated flux vectors for carbon sources partially predicts ancestral growth rate. Black dots indicate the growth rate of the two ancestral strains. A total of 268 reactions were predicted as necessary for optimal metabolism on glucose. (D) Hamming distance between a substrate and glucose does not correlate with increases or decreases in growth rate. The y axis is the log of the ratio of growth rate relative to the ancestor, with all ratios greater or less than e2 binned at the axis limit. For (C–D), purple dots are mutator strains, and orange dots are nonmutators. Larger dots at the axis extrema indicate more overlapping points, and the shading between purple and orange indicates the different proportions of mutators and nonmutators at that limit. For (B–D), substrates with the same x axis values were plotted with a slight offset, and the true value is listed in the axis label.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928024&req=5

pbio-1001789-g003: Substrate dissimilarity does not predict metabolic erosion.(A) A simple categorization of substrates as sugars and nonsugars finds that the correlation between relatedness to glucose and evolved metabolic changes is the opposite from what is hypothesized. (B) The FBA-predicted mutational target size does not correlate with decreases in growth rate. (C) Hamming distance between FBA-generated flux vectors for carbon sources partially predicts ancestral growth rate. Black dots indicate the growth rate of the two ancestral strains. A total of 268 reactions were predicted as necessary for optimal metabolism on glucose. (D) Hamming distance between a substrate and glucose does not correlate with increases or decreases in growth rate. The y axis is the log of the ratio of growth rate relative to the ancestor, with all ratios greater or less than e2 binned at the axis limit. For (C–D), purple dots are mutator strains, and orange dots are nonmutators. Larger dots at the axis extrema indicate more overlapping points, and the shading between purple and orange indicates the different proportions of mutators and nonmutators at that limit. For (B–D), substrates with the same x axis values were plotted with a slight offset, and the true value is listed in the axis label.
Mentions: We first tested whether evolved decreases in growth rate scaled with mutational target size. There is no expected behavior under this hypothesis for increases in growth rate, so we limited our analysis to combinations of strains and substrates for which growth rate had decreased. By identifying the reactions necessary for optimal growth on alternative substrates that are not necessary for growth on glucose, and determining the number of coding nucleotides necessary for those reactions, we were able to approximate the number of available mutations that would decrease growth rate on a substrate. Contrary to our hypothesis, we found no significant relationship between mutational target size and reduction in growth rate [p = 0.15, linear regression F test(1, 146) = 2.1] (Figure 3B).

Bottom Line: These reductions in growth by mutator strains were ameliorated by growth at lower temperature, consistent with the hypothesis that this metabolic erosion is largely caused by destabilizing mutations to the associated enzymes.To our surprise, we found no significant relationship between decreases in growth and dissimilarity to glucose metabolism.Taken as a whole, these data suggest that in a single resource environment, specialization does not mainly result as an inevitable consequence of adaptive tradeoffs, but rather due to the gradual accumulation of disabling mutations in unused portions of the genome.

View Article: PubMed Central - PubMed

Affiliation: Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, United States of America ; Systems Biology Graduate Program, Harvard University, Cambridge, Massachusetts, United States of America.

ABSTRACT
Evolutionary adaptation to a constant environment is often accompanied by specialization and a reduction of fitness in other environments. We assayed the ability of the Lenski Escherichia coli populations to grow on a range of carbon sources after 50,000 generations of adaptation on glucose. Using direct measurements of growth rates, we demonstrated that declines in performance were much less widespread than suggested by previous results from Biolog assays of cellular respiration. Surprisingly, there were many performance increases on a variety of substrates. In addition to the now famous example of citrate, we observed several other novel gains of function for organic acids that the ancestral strain only marginally utilized. Quantitative growth data also showed that strains with a higher mutation rate exhibited significantly more declines, suggesting that most metabolic erosion was driven by mutation accumulation and not by physiological tradeoffs. These reductions in growth by mutator strains were ameliorated by growth at lower temperature, consistent with the hypothesis that this metabolic erosion is largely caused by destabilizing mutations to the associated enzymes. We further hypothesized that reductions in growth rate would be greatest for substrates used most differently from glucose, and we used flux balance analysis to formulate this question quantitatively. To our surprise, we found no significant relationship between decreases in growth and dissimilarity to glucose metabolism. Taken as a whole, these data suggest that in a single resource environment, specialization does not mainly result as an inevitable consequence of adaptive tradeoffs, but rather due to the gradual accumulation of disabling mutations in unused portions of the genome.

Show MeSH
Related in: MedlinePlus