Rare variant alleles in the light of the neutral theory

Based on the neutral theory of molecular evolution and polymorphism, andparticularly assuming "the model of infinite alleles," a method is proposedwhich enables us to estimate the fraction of selectively neutral alleles(denoted by Pneut) among newly arisen mutations. It makes use of data onthe distribution of rare variant alleles in large samples together withinformation on the average heterozygosity. The formula proposed is Pneut =[He/(1-He)] [loge(2nq)/n alpha (x less than q)], where n alpha(x less thanq) is the average number of rare alleles per locus whose frequency, x, isless than q; n is the average sample size used to count rare alleles; He isthe average heterozygosity per locus; and q is a small preassigned numbersuch as q = 0.01. The method was applied to observations on enzyme andother protein loci in plaice, humans (European and Amerindian), Japanesemonkeys, and fruit flies. Estimates obtained for them range from 0.064 to0.21 with the mean and standard error Pneut = 0.14 +/- 0.06. It was pointedout that these estimates are consistent with the corresponding estimatePneut(Hb) = 0.14 obtained independently based on the neutral theory andusing data on the evolutionary rate of nucleotide substitutions in globinpseudogenes together with those in the normal globins.