Surviving the ratchet : Modelling deleterious mutations in asexual populations

Abstract: One of the most unforgiving processes in nature is that of Muller's ratchet, a seemingly irreversible accumulation of deleterious mutations that all organisms have to deal with or face extinction. The most obvious way to avoid fitness collapse is recombination, though asexual populations usually do not have the luxury of recombining freely.  With the aid of computational and mathematical models, we have studied other situations where this threat is averted and the organism can survive the ratchet. The results show that a ratchet where all mutations have the same deleterious fitness effect is very effectively stalled for large effects. However, if mutations are allowed to have a broad range of effects, the fitness-loss rate can be substantial even with the same mean effect as the one-type ratchet, but we have  identified parameter regions where even the broad-range effects are effectively stopped. The fitness-loss from a ratchet is very sensitive to the mutation rate and a mutation that increases the mutation rate (mutator) can easily start an otherwise stalled ratchet. Large effect mutators are heavily counter-selected, but smaller mutators can spread in the population. They can be stopped by reversals (antimutators), but even if the mutation rate is equilibrated in this way, there will be large fluctuations in mutation rate and even larger in the fitness-loss rate due to the feedback amplification in their coupling.    Another way of preventing the ratchet is by reversal of the deleterious mutations themselves through back-mutations or compensatory mutations. The rate required to stop the ratchet using only back-mutations before the fitness collapses is very large. A detailed comparison between the deleterious mutations in the ratchet and in a sexual population was made and the difference was found to be greatest for large populations with large genomes. There are obviously many ways to survive the ratchet, but even more ways to drive a species to extinction by enhancing and speeding up the ratchet. By modelling and testing the ratchet for numerous different situations, we show the effects of some of these threats and benefits.