The current status of REH theory.

The recent evaluation by Fitch (1980) of REH theory for macromolecular divergence is a severely erroneous and distorted analysis of our work over the past decade. We reply to those distortions here. At present, there is no factual basis for believing Fitch's assessment that corrections which move evolutionary estimates of total mutations fixed closer to the true distance must do so at the expense of an increased variance sufficient to compromise the value of the improvement. By direct calculation the variance in the estimates of total mutations fixed given by REH theory is comparable to that of other models now in the literature for the case in which genetic events are equiprobable. A general argument is given that suggests that, as we consider more and more carefully the selective, functional, and structural constraints on the evolution of genes and proteins, this variance may be expected to decrease toward a lower bound.