Selective neutrality and enzyme kinetics

This article appeals to a recent theory of enzyme evolution to show that the properties, neutral or adaptive, which characterize the observed allelic variation in natural populations can be inferred from the functional parameters, substrate specificity, and reaction rate. This study delineates the following relations between activity variables, and the forces--adaptive or neutral--determining allelic variation: (1) Enzymes with broad substrate specificity: The observed polymorphism is adaptive; mutations in this class of enzymes can result in increased fitness of the organism and hence be relevant for positive selection. (2) Enzymes with absolute substrate specificity and diffusion-controlled rates: Observed allelic variation will be absolutely neutral; mutations in this class of enzymes will be either deleterious or have no effect on fitness. (3) Enzymes with absolute or group specificity and nondiffusion-controlled rates: Observed variation will be partially neutral; mutants which are selectively neutral may become advantageous under an appropriate environmental condition or different genetic background. We illustrate each of the relations between kinetic properties and evolutionary states with examples drawn from enzymes whose evolutionary dynamics have been intensively studied.