• Circadian rhythm;
  • gene duplications;
  • isozymes;
  • Drosophila;
  • robustness;
  • canalization

Enzyme isoforms are found in many cellular reactions, and can differ in the kind of reaction they catalyze, in their substrate affinity, or in their reaction rates. The evolutionary significance of enzyme isoforms is only partially understood. We used mathematical modeling to investigate the hypothesis that isoforms may be favored by selection because they can increase the phenotypic robustness of the system. We modify a model for circadian clock gene expression in Drosophila to incorporate the presence of isoforms in the phosphorylation pathway of the period gene. We consider the case in which different isoforms catalyze the same reaction but have different affinities for the substrate. Stability is increased if there is dynamic control of the expression of isoforms relative to each other. Thus, we show that controlling isoform proportion can be a powerful mechanism for reducing the effects of variations in the values of system parameters, increasing system robustness.