The problem, the facts, and the neutralist solution

What is the mechanism by which genetic variability at the molecular level, such as manifested in the form of protein polymorphism, is maintained? This is the outstanding problem confronting present-day population genetics.

In the previous chapter (chapter 8) I have presented some models of molecular population genetics which were developed through the use of the diffusion equation method. It represents the neutralist program to treat this difficult but important problem. Furthermore, I have shown in quantitative terms, taking a hypothetical mammal as an example, how a realistic level and pattern of genetic variability can be predicted by assuming a set of parameter values derived from independent sources, such as the base substitution rate as estimated from the evolutionary study of globin pseudogenes, the fraction of neutral mutants among all mutations in the average protein as estimated by the frequency of rare electrophoretic variants, the average size of genes that code enzymes, and a reasonable guess about the effective population size in the long term evolution of a typical mammal. The central theme in this endeavor is that protein polymorphism and protein evolution are not two independent phenomena. Rather, protein polymorphism represents a transient phase of molecular evolution (Kimura and Ohta, 1971a).