Comparisons between the genomes of human and yeast reveal that there are numerous cases of genes whose function, and amino acid sequence, have been highly conserved through evolution, yet functional testing has shown that the regulatory elements in the promoters of these genes are completely different. To understand this apparent paradox between the evolution of a coding sequence and that of a promoter, the promoters of the genes encoding the glycolysis-related enzyme glucose-6-phosphate dehydrogenase (G6PD) and the structural molecule beta-actin will be characterized from model organisms which are descended from significant evolutionary points between yeast and humans. Comparative genomics will be combined with in vitro assays of both transcription factor binding and promoter-driven reporter gene expression to develop an understanding of how the promoters of these genes changed functionally through evolution. The results generated will be used to test recent hypotheses about the forces shaping the ion of the upstream regulatory region of a gene, and will allow the development of a general model of the constraints and dynamics of promoter evolution.
