Selective constraint in protein polymorphism: Study of the effectively neutral mutation model by using an improved pseudosampling method

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Abstract
To investigate the pattern of allelic distribution in enzyme polymorphism, with special reference to the relationship between the mean (.hivin.H) and the variance (VH) of heterozygosity, the model of effectively neutral mutations involving multiple alleles in which selective disadvantage of mutant alleles follows a .gamma. distribution was used. A simulation method was developed to study efficiently the process of random drift in a multiallelic genetic system and saves a great deal of computer time. It is an improved version of the pseudosampling-variable (PSV) method previously used to simulate random drift in a diallelic system. This method will be useful for simulating many models of population genetics that involve behavior of multiple alleles in a finite population. By using this method, as compared with the model of strictly neutral mutations, the present model gives the reduction of both .hivin.H and VH and an excess of rare variant alleles. Recent observations on protein polymorphism were discussed with special reference to the functional constraint of proteins involved.