Low Base-Substitution Mutation Rate but High Rate of Slippage Mutations in the Sequence Repeat-Rich Genome of <i>Dictyostelium discoideum</i>

Abstract We describe the rate and spectrum of spontaneous mutations for the social amoeba Dictyostelium discoideum, a key model organism in molecular, cellular, evolutionary and developmental biology. Whole-genome sequencing of 37 mutation accumulation lines of D. discoideum after an average of 1,500 cell divisions yields a base-substitution mutation rate of 2.47 × 10−11 per site per generation, substantially lower than that of most eukaryotic and prokaryotic organisms, and of the same order of magnitude as in the ciliates Paramecium tetraurelia and Tetrahymena thermophila. Known for its high genomic AT content and abundance of simple sequence repeats, we observe that base-substitution mutations in D. discoideum are highly A/T biased. This bias likely contributes both to the high genomic AT content and to the formation of simple sequence repeats in the AT-rich genome of Dictyostelium discoideum. In contrast to the situation in other surveyed unicellular eukaryotes, indel rates far exceed the base-substitution mutation rate in this organism with a high proportion of 3n indels, particularly in regions without simple sequence repeats. Like ciliates, D. discoideum has a large effective population size, reducing the power of random genetic drift, magnifying the effect of selection on replication fidelity, in principle allowing D. discoideum to evolve an extremely low base-substitution mutation rate.