Evolutionary impacts of DNA methylation on vertebrate genomes
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DNA methylation is an epigenetic modification in which a methyl group is covalently added to the DNA. In vertebrate genomes methylation occurs almost exclusively at cytosines immediately followed by a guanine (CpG dinucleotides). Two important aspects of DNA methylation have inspired several recent scientific investigations including those in this dissertation. First, methylated cytosines are hotspots of point mutation due to a methylation-dependent mutation mechanism, which has caused a deficiency of CpGs in vertebrate genomes. Second, DNA methylation in promoters is linked with transcriptional silencing of the associated genes. This dissertation presents the results of four studies in which I investigated the impacts of DNA methylation on the neutral and functional evolution of vertebrate genomes. The results of the first two studies demonstrate that DNA methylation has profound impacts on both inter- and intra-genomic neutral substitution rate variation. The third and fourth studies demonstrate that DNA methylation has played critical roles in shaping the evolution of vertebrate promoters and gene regulation.