Evolution of the rate, spectrum, and fitness effects of mutation under minimal selection in Caenorhabditis elegans

Evolution of mutation rate is of longstanding interest. The classical explanation is a Cost of Fidelity, which posits a tradeoff between selection to reduce deleterious mutations and selection to minimize resources devoted to genome surveillance. An alternative is the Drift Barrier, whereby the mutation rate is under directional selection downward; at equilibrium, the increase in fitness from a further increase in replication fidelity is too small to overcome genetic drift. We propagated C. elegans mutation accumulation (MA) lines under minimal selection for ~150 generations, divided each line into two sublines and propagated them for another ~150 generations. The base-substitution rate did not change, but variation among lines increased, as predicted by the CoF. Conversely, the insertion/deletion rate increased, as predicted by the DB. The base-substitution spectrum did not change, whereas the spectra of insertions and deletions did. Also of interest is the nature of selection on deleterious mutations. If epistasis is synergistic, several evolutionary quandaries could be resolved. To quantify mutational effects on fitness, and to characterize the pattern of epistasis, we assayed competitive fitness at 150 and 300 generations. Mutations had a mean effect of -0.1%, and a model of constant mutational effects (no epistasis) satisfactorily explains the results.