Mutational processes of simple-sequence repeat loci in human populations.

TLDR

Mutational processes of simple sequence repeats (SSRs) in complex genomes are poorly understood. The study examined SSR mutational processes by introducing a two‑phase mutation model under assumptions of neutrality and rapid population growth. They modeled SSR evolution with a two‑phase mutation process—predominantly single‑step changes with rare large jumps—using computer simulations to generate expected allele‑size statistics, then compared these to observed data from 10 loci in Sardinian, Egyptian, and sub‑Saharan African samples. The two‑phase model best fit most Sardinian loci, supporting distinct small‑change and rare large‑change mutation classes, and SSR‑based interpopulation distances were comparable to mitochondrial DNA estimates.

Abstract

Mutational processes of simple sequence repeats (SSRs) in complex genomes are poorly understood. We examined these processes by introducing a two-phase mutation model. In this model, most mutations are single-step changes, but infrequent large jumps in repeat number also occur. We used computer simulations to determine expected values of statistics that reflect frequency distributions of allele size for the two-phase model and two alternatives, the one-step and geometric models. The theoretical expectations for each model were tested by comparison with observed values for 10 SSR loci genotyped in the Sardinian population, whose genetic and demographic histories have been previously reconstructed. The two-phase model provided the best fit to the data for most of these loci in this population. In the analysis we assumed that the loci were neutral and that this population had undergone rapid population growth. Recent observations made for unstable trinucleotide repeats support our suggestion that frequent small changes and rare large changes in repeat number represent two distinct classes of mutation at SSR loci. We genotyped the same 10 loci in Egyptian and sub-Saharan African samples to assess the utility of SSRs for studying the divergence of populations and found that estimates of interpopulation distances from SSRs were similar to those derived from analysis of mitochondrial DNA.