Properties of spontaneous and induced mutations in Caenorhabditis elegans.

摘要

As the ultimate supplier of the genetic variation upon which natural selection acts, mutation holds a central role in evolutionary theory. Yet, despite its theoretical importance, there is still a conspicuous gap in our knowledge from an empirical perspective of the fundamental properties of mutation and its role in population-level processes. Using the nematode, Caenorhabditis elegans, as a model, I investigated properties of mutations that accumulated both as a result of natural mutagenic processes as well as mutations accrued in a DNA repair-deficient strain, msh-2. First, I performed an experiment to reveal the degree to which the cumulative effects of detrimental mutation can be expunged when a mutationally degraded population is maintained under a regime of large population size exposed to natural selection. Results demonstrated that, on average, mutation lines experienced essentially full recovery to the original fitness state in fewer than 80 generations of large population-size treatment and that this recovery was largely due to the accumulation of compensatory mutations.; Next, I explored the influence of population size on fitness-related characters with the goal of inferring properties of the distribution of mutational effects. Divergence experiments were conducted with lines of the mutator strain, msh-2, maintained in an array of population sizes. Findings suggested that the majority of mutations with detectable effects on laboratory fitness were highly deleterious and that most could be easily purged. A comparison of the mutation rate inferred from phenotypic analyses to that estimated from direct sequencing of DNA from experimental lines revealed the existence of a large class of mutations that must have been essentially neutral with respect to laboratory fitness.; Finally, I investigated the degree of pleiotropic integration of spontaneous mutations influencing an array of life-history, morphological and behavioral characters. Estimates of mutational correlations—a measurement of the direction and magnitude of pleiotropic gene action—as well as phenotypic and environmental correlations, were generated for each pair of characters expressed in long-term mutation lines. Results indicated that pleiotropy is extensive, with positive mutational correlations being common, but perhaps only within related suites of characters.; This dissertation includes my co-authored materials.