Kick-starting the ratchet: the fate of mutators in an asexual population.

Muller's ratchet operates in asexual populations without intergenomic recombination. In this case, deleterious mutations will accumulate and population fitness will decline over time, possibly endangering the survival of the species. Mutator mutations, i.e., mutations that lead to an increased mutation rate, will play a special role for the behavior of the ratchet. First, they are part of the ratchet and can come to dominance through accumulation in the ratchet. Second, the fitness-loss rate of the ratchet is very sensitive to changes in the mutation rate and even a modest increase can easily set the ratchet in motion. In this article we simulate the interplay between fitness loss from Muller's ratchet and the evolution of the mutation rate from the fixation of mutator mutations. As long as the mutation rate is increased in sufficiently small steps, an accelerating ratchet and eventual extinction are inevitable. If this can be countered by antimutators, i.e., mutations that reduce the mutation rate, an equilibrium can be established for the mutation rate at some level that may allow survival. However, the presence of the ratchet amplifies fluctuations in the mutation rate and, even at equilibrium, these fluctuations can lead to dangerous bursts in the ratchet. We investigate the timescales of these processes and discuss the results with reference to the genome degradation of the aphid endosymbiont Buchnera aphidicola.

Mutational interference and the progression of Muller's ratchet when mutations have a broad range of deleterious effects.

Deleterious mutations can accumulate in asexual haploid genomes through the process known as Muller's ratchet. This process has been described in the literature mostly for the case where all mutations are assumed to have the same effect on fitness. In the more realistic situation, deleterious mutations will affect fitness with a wide range of effects, from almost neutral to lethal. To elucidate the behavior of the ratchet in this more realistic case, simulations were carried out in a number of models, one where all mutations have the same effect on selection [one-dimensional (1D) model], one where the deleterious mutations can be divided into two groups with different selective effects [two-dimensional (2D) model], and finally one where the deleterious effects are distributed. The behavior of these models suggests that deleterious mutations can be classified into three different categories, such that the behavior of each can be described in a straightforward way. This makes it possible to predict the ratchet rate for an arbitrary distribution of fitness effects using the results for the well-studied 1D model with a single selection coefficient. The description was tested and shown to work well in simulations where selection coefficients are derived from an exponential distribution.