Motoo
Kimura's original arguments in 1968 for the significance
of neutral mutations and random drift were based in part
on the hemoglobin data presented by Zuckerkandl
and Pauling in 1965. In fact in 1971, Tomoko Ohta and
Motoo Kimura asserted that the "remarkable constancy
of the rate of amino acid substitutions in each protein
over a vast period of geologic time constitutes so far the
strongest evidence for the theory (Kimura 1968, King and
Jukes 1969) that the major cause of molecular evolution
is random fixation of selectively neutral or nearly neutral
mutations" (Ohta and Kimura 1971, p. 18). The reason
the constancy provided such strong support is that the neutral
theory provided a mechanism for that constancy--the prediction
of rate constancy followed easily from basic theoretical
commitments of Kimura and the neutralists. According to
the neutralists, the rate per generation of mutant substitutions
in a population (k) is equal to the mutation rate per gamete
(v): k = v.

This
result is derived as follows. In a population of actual
size N, there are 2Nv new mutations produced in the entire
population per generation. Only a certain fraction of these
new mutations will become established in the population--that
is only a certain fraction will reach fixation. Let "u"
represent he probability that a new mutation will reach
fixation. Then, in Kimura's words, "in a steady state
in which the process of substitution goes on for a very
long time, the rate k of mutant substitution per unit time
is given by the equation k = 2Nvu " (Kimura 1979, p.
108). For selectively neutral mutations, however, the probability
of fixation (u) is equal to 1/(2N), because "any one
of the 2N genes in the population is as likely as any other
to be fixed, and so the probability that the new mutant
will be the lucky one is 1/(2N)" (Kimura 1979, p. 108).
Substituting 1/(2N) for u in equation 2 yields equation
1, k = v. It is important to note here that the rate of
mutant substitution is independent of population size.

The
rate of evolution for selectively advantageous mutants,
in contrast to neutral mutants, is dependent on both population
size and selection pressure. Kimura uses a lengthy derivation
to show that for selectively advantageous mutants the equation
for the rate of evolution is k = 4Nsv (Kimura 1979, p. 110).
Thus, in order for a selectionist model to account for the
constancy of the rates of evolution it must show how constancy
is possible when the rates are strongly dependent on the
environment, as represented by the selection coefficient
s and the measure of population size N, which can be quite
variable. Under the selectionist model, the rates of molecular
evolution should show nearly the same variability as the
rates of phenotypic evolution. Unfortunately for the neutralists,
the rates of molecular evolution were found to be far from
uniform.