Random fluctuation of selection coefficients and the extent of nucleotide variation in human populations

It is well known that the selection coefficient of a mutant allele varies from generation to generation, and the effect of this factor on genetic variation has been studied by many theoreticians. However, no consensus has been reached. One group of investigators believes that fluctuating selection has an effect of enhancing genetic variation, whereas the other group contends that it has a diversity-reducing effect. In recent years, it has become possible to study this problem by using single nucleotide polymorphisms (SNPs) as well as exome sequence data. In this article we present the theoretical distributions of mutant nucleotide frequencies for the two models of fluctuating selection and then compare the distributions with the empirical distributions obtained from SNP and exome sequence data in human populations. Interestingly, both SNP and exome sequence data showed that the neutral mutation model fits the empirical distribution quite well. Furthermore, the mathematical models with diversity-enhancing and diversity-reducing effects also fit the empirical distribution reasonably well. This result implies that there is no need of distinguishing between the diversity-enhancing and diversity-reducing models of fluctuating selection and the nucleotide polymorphism in human populations can be explained largely by neutral mutations when long-term evolution is considered.