Muller's Ratchet & Mutation Accumulation

Muller's Ratchet

Muller's ratchet describes the irreversible accumulation of deleterious mutations in asexual populations. Without recombination, the class of individuals with the fewest mutations can be lost by genetic drift, clicking the "ratchet" forward one notch. Each click is irreversible: the least-loaded class cannot be recreated without beneficial back-mutations.

The Model

• Asexual reproduction: No recombination means mutation classes are independent lineages
• Deleterious mutations: Fitness declines as w(k) = (1-s)^k for k mutations
• Mutation-selection balance: Mutation rate U creates new mutations, selection removes them
• Stochastic loss: The zero-mutation class has finite size and can be lost by drift

Critical Threshold

The key parameter is the product NU, where N is population size and U is the genomic deleterious mutation rate. When NU ≪ 1, the zero-mutation class is small and vulnerable to loss. When NU ≫ 1, the class is large enough to resist stochastic loss. The ratchet clicks faster for:

• Smaller populations (lower N)
• Higher mutation rates (higher U)
• Weaker selection (lower s)

Biological Significance

Muller's ratchet explains the evolutionary advantage of sexual reproduction and recombination. Asexual lineages face an irreversible fitness decline, eventually leading to extinction. This process is particularly important for:

• Small asexual populations: Mitochondria, Y chromosomes, obligate asexuals
• RNA viruses: High mutation rates and small effective population sizes
• Endangered species: Low genetic diversity accelerates ratchet operation

Historical Context

Hermann Joseph Muller proposed this mechanism in 1964 to explain why sexual reproduction is ubiquitous despite its two-fold cost. The irreversibility of the ratchet demonstrates that sex provides an evolutionary advantage by allowing recombination to recreate low-mutation genotypes.