| Microsatellites, small direct nucleic acid repeats, are a ubiquitous feature of eukaryotic genomes. The high mutation rate of microsatellite loci has made them useful in genetic mapping and evolutionary studies. In addition, microsatellite loci are used as indicators of diseases associated with DNA repair defects and have been implicated as the causal agent of several human genetic diseases. Despite their widespread uses, little is known about the evolution of microsatellites and the factors that affect their frequency, distribution, and mutation. The recent completion of the Caenorhabditis elegans genome allows direct testing of many of the hypotheses concerning microsatellite evolution. In this dissertation all of the microsatellites within the Caenorhabditis elegans genome have been mapped in order to test hypotheses regarding the origin of microsatellite loci. Differences in microsatellite distribution within and among chromosomes do not appear to be related to recombination frequency, base composition or the density of coding regions. While no evidence exists for the seeding of microsatellite loci by retrotransposons, some Microsatellite loci appear to be related to the repeat sequences of Caenorhabditis elegans telomeres. Understanding the rates and patterns of Microsatellite mutation is critical for their use in studies of evolution, genetic mapping and mutational mechanisms. In order to understand the rates and patterns of mutation, 29 microsatellite loci were assayed in a set of 80 Caenorhabditis elegans mutation accumulation lines propagated for 140 generations. The pattern of Microsatellite variation in Caenorhabditis elegans is similar to that observed in yeast, suggesting that these patterns may be common features of Microsatellite evolution. The mismatch repair system is responsible for preventing mutations in Microsatellite loci. This dissertation identifies all of the genes in Caenorhabditis elegans homologous to the mismatch repair genes and discusses the evolution of this important family of proteins. The research reported in this dissertation rigorously examines all aspects of Microsatellite evolution in a model organism and lays the groundwork for future studies into understanding the mechanisms responsible for controlling Microsatellite mutation in other eukaryotes. |
