Date of Graduation

Fall 2009

Degree

Master of Science in Biology

Department

Biology

Committee Chair

John Heywood

Keywords

mutation rate, mutational meltdown, extinction, mutator, repair load

Subject Categories

Biology

Abstract

I analyzed the dynamics of the mutation rate in both finite and infinite randomly-mating populations. Germ-line mutator alleles, alleles that increase the genomic mutation rate, frequently occur when mutations alter the structure or regulation of genes involved in DNA repair, a fraction of the genome called the "repair genome”. The repair genome is a subset of the effective genome, the portion of the genome that affects any aspect of an organism's phenotype. The fraction of the effective genome that is the repair genome is equal to the probability that a mutation creates a mutator allele, given that the mutation is not neutral. In an infinite population with multiplicative fitness, the segregating load of mutator alleles increases indefinitely when the relative size of the repair genome exceeds the mean selective coefficient against mutations to the remainder of the effective genome. This occurs because the probability of creating new mutator alleles exceeds the probability of selective elimination of those alleles. This process, which I call "deterministic mutational meltdown,” places an upper limit on the relative size of the repair genome. The tendency of mutator alleles to recruit new mutator alleles, which I call "positive-feedback mutation pressure,” affects the mutation dynamics of any organism. If an undamaged repair genome allows a non-zero mutation rate, then a stable segregating mutator load increases the mutation rate by an amount that depends on the relative size of the repair genome and the mean selection coefficient. The effect of drift on the mutation rate increases with the mutation rate and is inversely proportional to population size. Positive-feedback mutation pressure increases the probability of stochastic mutational meltdown in small populations and decreases the mean time to extinction.

Copyright

© Matthew Steven Ackerman

Campus Only

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