MULLERS RATCHET, EPISTASIS AND MUTATION EFFECTS

In this study, computer simulation is used to show that despite synerg istic epistasis for fitness, Muller's ratchet can lead to lethal fitne ss loss in a population of asexuals through the accumulation of delete rious mutations. This result contradicts previous work that indicated that epistasis will halt the ratchet. The present results show that ep istasis will not hale the ratchet provided that rather than a single d eleterious mutation effect, there is a distribution of deleterious mut ation effects with sufficient density near zero. In addition to epista sis and mutation distribution, the ability of Muller's ratchet to lead to the extinction of an asexual population under epistasis for fitnes s depends strongly on the expected number of offspring that survive to reproductive age. This strong dependence is not present in the nonepi static model and suggests that interpreting the population growth para meter as fecundity is inadequate. Because a continuous distribution of mutation effects is used in this model, an emphasis is placed on the dynamics of the mutation effect distribution rather than on the dynami cs of the number of least mutation loaded individuals. This perspectiv e suggests that current models of gene interaction are too simple to a pply directly to long-term prediction for populations undergoing the r atchet.