The indirect estimation of mutation rates in man

Abstract

The need for generating reliable estimates of mutation rate in man has been emphasized by a number of geneticists. The present study estimates the rate of mutation at cistron level using data on electromorphs in a number of human populations. The number and frequency of private electromorphs, both rare and polymorphic, have been enumerated in relatively isolated populations from Australia, Papua New Guinea, India and. sub- Saharan Africa. It. is noticed that the recovery of these electrophoretic variants is directly related to the number of genes sampled, the size of the polypeptide subunit electrophoresed and the molecular constraints arising from the assembly of multimeric proteins. Mutation rates in 38 individual populations have been generated in the present study by five different methods. The average estimates of mutation rate obtained by the methods of Kimura and Ohta (1969) and Rothman and Adams (1978) are 5.99x10 ^ and 6.39x10 ^/locus per generation respectively. The estimates by the rare allele methods of Nei (1977) and Chakraborty (1981) and by a new method, suggested in the present study, utilizing singletons, are comparatively smaller, being 4.62x10 2.55x10 ^ and 2.86x10 locus per generation respectively. The estimates of mutation rate generated here show regional/ethnic differences. The significance of these differences, however, cannot be properly evaluated since large standard errors are known to be associated with the estimates of the number of alleles segregating and the population size, two of the parameters indispensible to the indirect approaches. The suggestion of Nei et al. (1976b) regarding the variability in mutation rates of various protein loci has been tested using the data on rare alleles in 12 different human populations. The results indicate the existence of significant correlation between subunit molecular weights and the number and frequency of rare alleles. The present results have indicated the existence of variability in the estimates of mutation rate more or less at the same level as that generated from indirect estimates of "classical" traits. The need for deciding the order of magnitude of mutation rate in man is alive as ever