Remember, this was in 1968 and we didn't know as much then as we do now. Kimura took note of the fact that evolutionary trees based on comparing amino acid sequences gave rates of amino acid substitutions that seemed far too high. His conclusion is in the abstract.
Calculating the rate of evolution in terms of nucleotide substitutions seems to give a value so high that many of the mutations involved must be neutral ones.This is the beginning of Neutral Theory and we now know that his conclusion is correct.
Kimura wanted to know if there was any independent, supporting, evidence for the estimated mutation rates from amino acid substitutions so he looked to the error rate of DNA replication.
In the first edition of The Molecular Biology of the Gene Jim Watson had estimated the overall error rate for DNA replication at 10-8 to 10-9 per nucleotide. This was based partly on Seymour Benzer's saturation mapping of the rII locus in bacteriophage T4 [see Wikipedia: T4 rII system]. Kimura figured that there were about 50 cell divisions in the lineage from gamete to fertilized egg so he estimated that if the human genome was 4 × 109 bp then there would be somewhere between 200 and 2000 mutations per generation in humans.
Watson's error rate was too high. We know know that it's closer to 10-10. Kimura's guesstimate of 50 cell divisions is too low because we now know that there are about 400 cell divisions during production of sperm and 30 cell division in the production of egg cells for an average of 215 [Estimating the Human Mutation Rate: Biochemical Method]. Kimura also over-estimated the size of the human genome—in this case he should have known the correct value (3.2 × 109).
Nevertheless, he ended up with a value of 200 for the lower bound based on the lowest error rate and this isn't too far off the current estimate (130 mutations per generation). Not bad for the 60s!
Now back to our regularly scheduled programming ....
Kimura knew what his calculation meant.
Finally, if my chief conclusion is correct, and if the neutral or nearly neutral mutation is being produced in each generation at a much higher rate than has been considered before, then we must recognize the great importance of random genetic drift due to finite population number in forming the genetic structure of biological populations, The significance of random genetic drift has been deprecated during the past decade. This attitude has been influenced by the opinion that almost no mutations are neutral, and also that the large number of individuals forming a species is usually so large that random sampling of gametes should be negligible in determining the course of evolution, except possibly through the "founder principle." [reference to Ernst Mayr].Now, Kimura obviously doesn't think much of those people who deny neutral mutations and the importance of random genetic drift so he makes an analogy.
To emphasize the founder principle but deny the importance of random genetic drift due to finite population number is, in my opinion, rather similar to assuming a great flood to explain the formation of deep valleys but rejecting a gradual but long lasting process of erosion by water as insufficient to produce such a result.There are still a lot of scientists acting like flood geologists.
Here's a photo for all you evolution fans. It shows James ("Jim") Crow, R.A. Fisher, and Motoo Kimura in Crow's lab at the University of Wisconsin in 1961.1
Image Credit: the cartoon is from: Robins depot
1. I was going to post a good song from 1961 but there weren't any ... except maybe 'Hats off to Larry' #68 by Del Shannon.
Kimura, M. (1968) Evolutionary rate at the molecular level. Nature, 217:624-626. [PDF]