Fig. 2.

The evolution and consequences of metabolic control, see text. (A) When fitness is proportional to flux the mean activity will increase through mutation until the incremental advance in fitness, Δw, is of the order of the reciprocal of the effective population size, 1/N_e. At this point the mutation substitution rate converges on the neutral substitution rate and mean activity stalls. (B) Two different enzymes with different control functions and, as a consequence, different activity ranges over which mutational reductions qualify as neutral. Gene 2E will accommodate more neutral mutation than gene 5E. (C) The effect of changing the metabolic control function for 2E. In this case mutations, formerly with neutral fitness effects, will be purged by natural selection. (D) The effect of decreasing population size. This lowers the neutral fitness threshold and increases the activity range over which mutations are effectively neutral. The rate of neutral mutation substitution will increase, as will polymorphism.