Low Base-Substitution Mutation Rate but High Rate of Slippage Mutations in the Sequence Repeat-Rich Genome ofDictyostelium discoideum

We describe the rate and spectrum of spontaneous mutations for the social amoebaDictyostelium discoideum, a key model organism in molecular, cellular, evolutionary and developmental biology. Whole-genome sequencing of 37 mutation accumulation lines ofD. discoideumafter an average of 1,500 cell divisions yields a base-substitution mutation rate of 2.47 x 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 ciliatesParamecium tetraureliaandTetrahymena thermophila. Known for its high genomic AT content and abundance of simple sequence repeats, we observe that base-substitution mutations inD. discoideumare 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 ofDictyostelium 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. discoideumhas a large effective population size, reducing the power of random genetic drift, magnifying the effect of selection on replication fidelity, in principle allowingD. discoideumto evolve an extremely low base-substitution mutation rate.