Molecular population genetics and selection in the glycolytic pathway

In this review, I discuss the evidence for differential natural selection acting across enzymes in the glycolytic pathway in Drosophila. Across the genome, genes evolve at very different rates and possess markedly varying levels of molecular polymorphism, codon bias and expression variation. Discovering the underlying causes of this variation has been a challenge in evolutionary biology. It has been proposed that both the intrinsic properties of enzymes and their pathway position have direct effects on their molecular evolution, and with the genomic era the study of adaptation has been taken to the level of pathways and networks of genes and their products. Of special interest have been the energy-producing pathways. Using both population genetic and experimental approaches, our laboratory has been engaged in a study of molecular variation across the glycolytic pathway in Drosophila melanogaster and its close relatives. We have observed a pervasive pattern in which genes at the top of the pathway, especially around the intersection at glucose 6-phosphate, show evidence for both contemporary selection, in the form of latitudinal allele clines, and inter-specific selection, in the form of elevated levels of amino acid substitutions between species. To further explore this question, future work will require corroboration in other species, expansion into tangential pathways, and experimental work to better characterize metabolic control through the pathway and to examine the pleiotropic effects of these genes on other traits and fitness components.