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Increased glycolytic flux as an outcome of whole-genome duplication in yeast.

Conant GC, Wolfe KH - Mol. Syst. Biol. (2007)

Bottom Line: We propose that the loss of other redundant genes throughout the genome resulted in incremental dosage increases for the surviving duplicated glycolytic genes.Because changes in gene dosage follow directly from post-WGD deletions, dosage selection can confer an almost instantaneous benefit after WGD, unlike neofunctionalization or subfunctionalization, which require specific mutations.We also show theoretically that increased fermentative capacity is of greatest advantage when glucose resources are both large and dense, an observation potentially related to the appearance of angiosperms around the time of WGD.

View Article: PubMed Central - PubMed

Affiliation: Smurfit Institute of Genetics, Trinity College, University of Dublin, Dublin, Ireland. conantg@tcd.ie

ABSTRACT
After whole-genome duplication (WGD), deletions return most loci to single copy. However, duplicate loci may survive through selection for increased dosage. Here, we show how the WGD increased copy number of some glycolytic genes could have conferred an almost immediate selective advantage to an ancestor of Saccharomyces cerevisiae, providing a rationale for the success of the WGD. We propose that the loss of other redundant genes throughout the genome resulted in incremental dosage increases for the surviving duplicated glycolytic genes. This increase gave post-WGD yeasts a growth advantage through rapid glucose fermentation; one of this lineage's many adaptations to glucose-rich environments. Our hypothesis is supported by data from enzyme kinetics and comparative genomics. Because changes in gene dosage follow directly from post-WGD deletions, dosage selection can confer an almost instantaneous benefit after WGD, unlike neofunctionalization or subfunctionalization, which require specific mutations. We also show theoretically that increased fermentative capacity is of greatest advantage when glucose resources are both large and dense, an observation potentially related to the appearance of angiosperms around the time of WGD.

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(A) Changes in the concentration of key metabolites in response to overall decreases in the Vmax values for the reactions of glycolysis (blue, left axis scale), as well as the change in PYK flux over the same range (red, right axis scale). (B) Ratio of the flux through pyruvate decarboxylase (PDC, fermentative pathways) to the flux through pyruvate dehydrogenase (PDH, respiratory pathway) as a function of pyruvate concentration and the ratio of NAD+ to NADH concentration (because NAD+ and NADH are two oxidation states of the same molecule, their concentrations vary inversely and hence are constrained to sum to 8.01 in B; Theobald et al, 1997). (C) Effect of compartmentalization on the relative fluxes of the first reaction in respiration (PDH) and in fermentation (PDC). On the x-axis is the relative enzyme concentration modeling a change from a rough pre-duplication state of 0.65 to a post-duplicate value of 1.0 (see A). On the y-axis is given the ratio of the fluxes between the two reactions relative to the flux when [E] on the x-axis is equal to 1.0.
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f2: (A) Changes in the concentration of key metabolites in response to overall decreases in the Vmax values for the reactions of glycolysis (blue, left axis scale), as well as the change in PYK flux over the same range (red, right axis scale). (B) Ratio of the flux through pyruvate decarboxylase (PDC, fermentative pathways) to the flux through pyruvate dehydrogenase (PDH, respiratory pathway) as a function of pyruvate concentration and the ratio of NAD+ to NADH concentration (because NAD+ and NADH are two oxidation states of the same molecule, their concentrations vary inversely and hence are constrained to sum to 8.01 in B; Theobald et al, 1997). (C) Effect of compartmentalization on the relative fluxes of the first reaction in respiration (PDH) and in fermentation (PDC). On the x-axis is the relative enzyme concentration modeling a change from a rough pre-duplication state of 0.65 to a post-duplicate value of 1.0 (see A). On the y-axis is given the ratio of the fluxes between the two reactions relative to the flux when [E] on the x-axis is equal to 1.0.

Mentions: To a first approximation, reaction rates for an enzyme catalyzed reaction depend on two enzyme-specific parameters: Km, the substrate concentration that gives a half maximal reaction rate, which is essentially independent of enzyme concentration, and Vmax, the maximal reaction velocity. Vmax depends on factors such as the activation energy of the reaction and the concentration of the catalyzing enzyme. We modeled the effects of WGD on glycolysis by representing the implied ancestral enzyme concentrations for glycolysis and alcohol fermentation as uniform reductions in their Vmax values. As enzyme concentrations increase from 65 to 100% of their current levels (see Supplementary methods), the concentration of several metabolic intermediates increases, with pyruvate showing a 17% increase in concentration (Figure 2A). Perhaps even more significantly, the flux through the final reaction in glycolysis (i.e., pyruvate kinase, CDC19 and PYK2 in Figure 1) increases by a factor of two across the range of enzyme concentrations considered (red line in Figure 2A).


Increased glycolytic flux as an outcome of whole-genome duplication in yeast.

Conant GC, Wolfe KH - Mol. Syst. Biol. (2007)

(A) Changes in the concentration of key metabolites in response to overall decreases in the Vmax values for the reactions of glycolysis (blue, left axis scale), as well as the change in PYK flux over the same range (red, right axis scale). (B) Ratio of the flux through pyruvate decarboxylase (PDC, fermentative pathways) to the flux through pyruvate dehydrogenase (PDH, respiratory pathway) as a function of pyruvate concentration and the ratio of NAD+ to NADH concentration (because NAD+ and NADH are two oxidation states of the same molecule, their concentrations vary inversely and hence are constrained to sum to 8.01 in B; Theobald et al, 1997). (C) Effect of compartmentalization on the relative fluxes of the first reaction in respiration (PDH) and in fermentation (PDC). On the x-axis is the relative enzyme concentration modeling a change from a rough pre-duplication state of 0.65 to a post-duplicate value of 1.0 (see A). On the y-axis is given the ratio of the fluxes between the two reactions relative to the flux when [E] on the x-axis is equal to 1.0.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1943425&req=5

f2: (A) Changes in the concentration of key metabolites in response to overall decreases in the Vmax values for the reactions of glycolysis (blue, left axis scale), as well as the change in PYK flux over the same range (red, right axis scale). (B) Ratio of the flux through pyruvate decarboxylase (PDC, fermentative pathways) to the flux through pyruvate dehydrogenase (PDH, respiratory pathway) as a function of pyruvate concentration and the ratio of NAD+ to NADH concentration (because NAD+ and NADH are two oxidation states of the same molecule, their concentrations vary inversely and hence are constrained to sum to 8.01 in B; Theobald et al, 1997). (C) Effect of compartmentalization on the relative fluxes of the first reaction in respiration (PDH) and in fermentation (PDC). On the x-axis is the relative enzyme concentration modeling a change from a rough pre-duplication state of 0.65 to a post-duplicate value of 1.0 (see A). On the y-axis is given the ratio of the fluxes between the two reactions relative to the flux when [E] on the x-axis is equal to 1.0.
Mentions: To a first approximation, reaction rates for an enzyme catalyzed reaction depend on two enzyme-specific parameters: Km, the substrate concentration that gives a half maximal reaction rate, which is essentially independent of enzyme concentration, and Vmax, the maximal reaction velocity. Vmax depends on factors such as the activation energy of the reaction and the concentration of the catalyzing enzyme. We modeled the effects of WGD on glycolysis by representing the implied ancestral enzyme concentrations for glycolysis and alcohol fermentation as uniform reductions in their Vmax values. As enzyme concentrations increase from 65 to 100% of their current levels (see Supplementary methods), the concentration of several metabolic intermediates increases, with pyruvate showing a 17% increase in concentration (Figure 2A). Perhaps even more significantly, the flux through the final reaction in glycolysis (i.e., pyruvate kinase, CDC19 and PYK2 in Figure 1) increases by a factor of two across the range of enzyme concentrations considered (red line in Figure 2A).

Bottom Line: We propose that the loss of other redundant genes throughout the genome resulted in incremental dosage increases for the surviving duplicated glycolytic genes.Because changes in gene dosage follow directly from post-WGD deletions, dosage selection can confer an almost instantaneous benefit after WGD, unlike neofunctionalization or subfunctionalization, which require specific mutations.We also show theoretically that increased fermentative capacity is of greatest advantage when glucose resources are both large and dense, an observation potentially related to the appearance of angiosperms around the time of WGD.

View Article: PubMed Central - PubMed

Affiliation: Smurfit Institute of Genetics, Trinity College, University of Dublin, Dublin, Ireland. conantg@tcd.ie

ABSTRACT
After whole-genome duplication (WGD), deletions return most loci to single copy. However, duplicate loci may survive through selection for increased dosage. Here, we show how the WGD increased copy number of some glycolytic genes could have conferred an almost immediate selective advantage to an ancestor of Saccharomyces cerevisiae, providing a rationale for the success of the WGD. We propose that the loss of other redundant genes throughout the genome resulted in incremental dosage increases for the surviving duplicated glycolytic genes. This increase gave post-WGD yeasts a growth advantage through rapid glucose fermentation; one of this lineage's many adaptations to glucose-rich environments. Our hypothesis is supported by data from enzyme kinetics and comparative genomics. Because changes in gene dosage follow directly from post-WGD deletions, dosage selection can confer an almost instantaneous benefit after WGD, unlike neofunctionalization or subfunctionalization, which require specific mutations. We also show theoretically that increased fermentative capacity is of greatest advantage when glucose resources are both large and dense, an observation potentially related to the appearance of angiosperms around the time of WGD.

Show MeSH
Related in: MedlinePlus