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

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. Gene duplication has long been recognized as an important route to evolutionary novelty and increased organismal complexity. It has also been recognized that the different scales of possible duplications have the potential to generate differing kinds of novel adaptations. New proteins may evolve from single‐gene duplications, while larger duplications, including WGDs, can, in addition, allow more global restructuring of regulatory or metabolic networks in the organism. We describe a potential example of such a global change after a WGD in the bakers’ yeast, S. cerevisiae. The pathway in question is one of the most central in eukaryotes: glycolysis. Our analysis was initially prompted by an apparently different pattern of duplicate gene loss in the glycolytic pathway after WGD, as compared to the remainder of the genome. After WGD, many duplicate genes were lost rapidly, such that, today, only 10% of the duplicates created by WGD survive in S. cerevisiae. However, we show that genes coding for enzymes in the glycolytic pathway are significantly more like to be retained in duplicate than genes in the genome at large (with approximately 45% of the genes in the pathway preserved). Moreover, those genes involved in glycolysis that were preserved in duplicate tend to have greater impact on flux than their non‐duplicated counterparts, according to a mathematical model of glycolysis that we adapt. One potential explanation for this pattern of preservation in selection for gene dosage, whereby certain genes are maintained in duplicate because of a requirement for more copies of the proteins they code for. This possibility is of particular interest because it may relate to one of the more intriguing features of the physiology of bakers’ yeast. This yeast is unusual in that it prefers to ferment glucose to ethanol in the presence of oxygen rather than using the apparently more efficient respiratory pathways. Interestingly, several previous studies of fermentation in S. cerevisiae and related species have seemed to indicate a trend toward increased importance of fermentation around the time of the WGD. We argue that the WGD and consequent changes in glycolytic enzyme concentrations may first have increased the overall flux through glycolysis. Because a cell's rate of respiration depends on many complex factors, including the size and location of the mitochondria, the concentration of oxygen and the kinetics of the enzymes involved, we argue that WGD would have had a much less pronounced effect on the rate of respiration than on that of fermentation. Indeed, several mutant strains of yeast seem to support this hypothesis: reducing the concentration of glycolytic enzymes increases the relative importance of respiration, increasing these concentrations decreases its importance. Thus, we believe that the bakers’ yeast's preference for fermentation was enhanced by WGD. This possibility may seem counter‐intuitive, given the greater efficiency (in terms of moles of ATP produced per mole of glucose) of respiration. However, we illustrate an example of the well‐known phenomenon where a less efficient, but faster growing population has a competitive advantage over a more efficient one (the ‘tragedy of the commons’). This selective advantage may have even been the reason the WGD survived and became fixed, as its survival is otherwise difficult to explain. Thus, in addition to suggesting how an important physiological change in an organism can be wrought by a duplication, our example provides a plausible mechanism by which evolution can generate a complex new adaptation.