Polymorphism and protein evolution. The neutral mutation-random drift hypothesis.

In recent years many examples of what are conveniently referred to as enzyme and protein polymorphisms have been discovered in the course of surveys of human populations and of naturally occurring populations of other animal species. The term polymorphism is used in this context for any situation where members of a population can be sharply classified into several distinct phenotypes in terms of particular characteristics of the enzyme or protein, and where at least two of the phenotypes have an appreciable incidence (greater than 2%). Most of these polymorphisms can be attributed to the occurrence of two or more alleles each coding for a structurally distinct form of a polypeptide chain in the particular enzyme or protein. It is thought that the structural difference between the polypeptides usually amounts to no more than a single amino-acid substitution, and that the allelic difference originated in a single mutational event involving the change of only one base for another in the sequence of several hundred or thousand bases in the DNA of the particular gene. But direct evidence for this has so far only been obtained in a limited number of polymorphisms, and there are certainly some exceptions where the polypeptide products of the two common alleles differ by more than one amino acid, eg, the sheep haemoglobins A and B (Boyer et al, 1967). Electrophoretic surveys of arbitrarily chosen enzymes and proteins have been carried out in various naturally occurring animal populations to see how often such polymorphisms occur. A number of very different species have been studied in this way. They include man (Harris, 1966 and 1969), Drosophila pseudoobscura (Hubby and Lewontin, 1966; Lewontin, and Hubby, 1966; Prakash, Lewontin, and Hubby, 1969), mouse (Ruddle et al, 1969; Selander, Hunt, and Yang,