Simple method for analyzing the pattern of DNA polymorphism and its application to SNP data of human

Abstract

In order to analyze the pattern of DNA polymorphism in detail, we have developed a simple method using a new statistic θi which estimates 4Nμ from the number of segregating sites whose allelic nucleotide frequency is i/n among n DNA sequences, where N is the effective population size and μ is the mutation rate per generation per nucleotide site. Under the assumption that mutations are selectively neutral and a population size is constant, the expectation of θi is equal to that of θ, which estimates 4Nμ from the number of segregating sites, so that the distribution of θi is flat. Therefore, the departure of the distribution of θi from the horizontal line, which represents the value of θ, reflects change in population size and natural selection. Results of the coalescent simulation show that the distributions of θi in the populations which experienced expansion and reduction are U-shaped and upside-down U-shaped, respectively. And the distributions of θi in some populations that experienced bottleneck are W-shaped. Furthermore, we have applied this method to the SNP data in the International HapMap Project. Results of data analyses show that the distributions of θi in the CEU (European), CHB and JPT (Asian) populations are different from that in the YRI population (African). From these results of data analyses in nuclear DNA and the pattern of polymorphism in human mitochondrial DNA already known, we infer that the CEU, CHB and JPT populations experienced the bottleneck.