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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) Effect on flux through glycolysis (PYK flux) when the maximal enzymatic rates (Vmax) for the 10 relevant enzymes are individually reduced. Note that the TPI reaction is assumed to be at equilibrium and is not included in this analysis. On the x-axis are plotted the 10 reactions in question sorted in order of their effect on flux. On the y-axis is plotted the reduction in flux when Vmax is reduced by 10% for the reaction in question. Red bars indicate genes preserved in duplicate since WGD as well as the HXT genes (see text). PFK values are shown in green, as this reaction is catalyzed by a pair of more ancient duplicates. The blue bar indicates a WGD pair of enzymes in S. cerevisiae that is not maintained across all four post-WGD species (GPM). Bars in black are single-copy genes in S. cerevisiae. Flux through PYK for the unaltered model was 136.1 mmol/l/min (dashed line). (B) Effect on flux through glycolysis (PYK flux) when Vmax is first reduced to 75% of the current value for all reactions, and then individually increased to 100% of the current value for a single reaction. Thus the y-axis gives the flux through the pathway when all reactions except the one indicated have had their Vmax reduced to 75% of the current value. Reactions are shown in the same order as in panel A for comparison. The dashed line indicates the flux through PYK of 90.2 mmol/l/min seen when all enzymes have their Vmax values reduced to 75% of the current value.
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f3: (A) Effect on flux through glycolysis (PYK flux) when the maximal enzymatic rates (Vmax) for the 10 relevant enzymes are individually reduced. Note that the TPI reaction is assumed to be at equilibrium and is not included in this analysis. On the x-axis are plotted the 10 reactions in question sorted in order of their effect on flux. On the y-axis is plotted the reduction in flux when Vmax is reduced by 10% for the reaction in question. Red bars indicate genes preserved in duplicate since WGD as well as the HXT genes (see text). PFK values are shown in green, as this reaction is catalyzed by a pair of more ancient duplicates. The blue bar indicates a WGD pair of enzymes in S. cerevisiae that is not maintained across all four post-WGD species (GPM). Bars in black are single-copy genes in S. cerevisiae. Flux through PYK for the unaltered model was 136.1 mmol/l/min (dashed line). (B) Effect on flux through glycolysis (PYK flux) when Vmax is first reduced to 75% of the current value for all reactions, and then individually increased to 100% of the current value for a single reaction. Thus the y-axis gives the flux through the pathway when all reactions except the one indicated have had their Vmax reduced to 75% of the current value. Reactions are shown in the same order as in panel A for comparison. The dashed line indicates the flux through PYK of 90.2 mmol/l/min seen when all enzymes have their Vmax values reduced to 75% of the current value.

Mentions: Under our first two hypotheses, the glycolytic enzymes whose genes were retained in duplicate after WGD were preserved to increase the flux through glycolysis (i.e., for dosage reasons). We would thus expect a strong relationship between whether an enzyme is present in duplicate and that enzyme's impact on flux. To test this hypothesis, we studied the effect on PYK flux of individually reducing the Vmax of all the glycolytic enzymes (and the hexose transporters) to 90% of their current values. As Figure 3A shows, the genes that remain in duplicate in all four post-WGD species (HXT, HXK/GLK, TDH, ENO and PYK) are, with the exception of PYK, also those enzymes that cause the greatest reduction in flux if their Vmax values (a proxy for concentration) are reduced. CDC19/PYK2 is an exception to this rule, probably because these enzymes are strongly induced in a feed-forward mechanism by fructose-1-6-bisphosphate (Hess and Haeckel, 1967), a metabolic intermediate whose steady-state concentration increases when the Vmax of the PYK reaction is reduced (data not shown).


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

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

(A) Effect on flux through glycolysis (PYK flux) when the maximal enzymatic rates (Vmax) for the 10 relevant enzymes are individually reduced. Note that the TPI reaction is assumed to be at equilibrium and is not included in this analysis. On the x-axis are plotted the 10 reactions in question sorted in order of their effect on flux. On the y-axis is plotted the reduction in flux when Vmax is reduced by 10% for the reaction in question. Red bars indicate genes preserved in duplicate since WGD as well as the HXT genes (see text). PFK values are shown in green, as this reaction is catalyzed by a pair of more ancient duplicates. The blue bar indicates a WGD pair of enzymes in S. cerevisiae that is not maintained across all four post-WGD species (GPM). Bars in black are single-copy genes in S. cerevisiae. Flux through PYK for the unaltered model was 136.1 mmol/l/min (dashed line). (B) Effect on flux through glycolysis (PYK flux) when Vmax is first reduced to 75% of the current value for all reactions, and then individually increased to 100% of the current value for a single reaction. Thus the y-axis gives the flux through the pathway when all reactions except the one indicated have had their Vmax reduced to 75% of the current value. Reactions are shown in the same order as in panel A for comparison. The dashed line indicates the flux through PYK of 90.2 mmol/l/min seen when all enzymes have their Vmax values reduced to 75% of the current value.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: (A) Effect on flux through glycolysis (PYK flux) when the maximal enzymatic rates (Vmax) for the 10 relevant enzymes are individually reduced. Note that the TPI reaction is assumed to be at equilibrium and is not included in this analysis. On the x-axis are plotted the 10 reactions in question sorted in order of their effect on flux. On the y-axis is plotted the reduction in flux when Vmax is reduced by 10% for the reaction in question. Red bars indicate genes preserved in duplicate since WGD as well as the HXT genes (see text). PFK values are shown in green, as this reaction is catalyzed by a pair of more ancient duplicates. The blue bar indicates a WGD pair of enzymes in S. cerevisiae that is not maintained across all four post-WGD species (GPM). Bars in black are single-copy genes in S. cerevisiae. Flux through PYK for the unaltered model was 136.1 mmol/l/min (dashed line). (B) Effect on flux through glycolysis (PYK flux) when Vmax is first reduced to 75% of the current value for all reactions, and then individually increased to 100% of the current value for a single reaction. Thus the y-axis gives the flux through the pathway when all reactions except the one indicated have had their Vmax reduced to 75% of the current value. Reactions are shown in the same order as in panel A for comparison. The dashed line indicates the flux through PYK of 90.2 mmol/l/min seen when all enzymes have their Vmax values reduced to 75% of the current value.
Mentions: Under our first two hypotheses, the glycolytic enzymes whose genes were retained in duplicate after WGD were preserved to increase the flux through glycolysis (i.e., for dosage reasons). We would thus expect a strong relationship between whether an enzyme is present in duplicate and that enzyme's impact on flux. To test this hypothesis, we studied the effect on PYK flux of individually reducing the Vmax of all the glycolytic enzymes (and the hexose transporters) to 90% of their current values. As Figure 3A shows, the genes that remain in duplicate in all four post-WGD species (HXT, HXK/GLK, TDH, ENO and PYK) are, with the exception of PYK, also those enzymes that cause the greatest reduction in flux if their Vmax values (a proxy for concentration) are reduced. CDC19/PYK2 is an exception to this rule, probably because these enzymes are strongly induced in a feed-forward mechanism by fructose-1-6-bisphosphate (Hess and Haeckel, 1967), a metabolic intermediate whose steady-state concentration increases when the Vmax of the PYK reaction is reduced (data not shown).

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