The population genetics of alleles affecting enzyme activity

Abstract

It is possible to predict the population genetics of allozymes by assuming that fitness is proportional to flux through a biochemical pathway. The model presented here extends previous work by incorporating two additional features of biological realism. Firstly, that more than one biochemical route may exist between any two metabolites. The major routes have been identified as the classical biochemical pathways but in the event of a mutation blocking a major route, minor routes become significant. These minor routes are named "bypass fluxes" and have profound effects on the population genetics of allozymes. Secondly, recent work has suggested that a metabolic cost is associated with enzyme synthesis; this will constitute an additional selective pressure on alleles which affect the amount of enzyme synthesized. The model generates a fitness curve which predicts the fitness associated with any level of enzyme activity. It can utilize data on null or near-null, structural or regulatory, mutations in the presence or absence of bypass fluxes. When data from natural populations of Drosophila are investigated, it is concluded that selection pressures acting on enzyme variants may be much higher than previously thought.