The mechanisms that regulate gene expression are complex, however many features have been well-conserved through evolution. This dissertation discusses three main topics: (1) the genomic structure of the RGM family of genes, (2) the mechanisms of transcriptional and post-transcriptional regulation focusing on RGMc, and (3) the molecular evolution of the RGM family. The long-range and overarching goal of this dissertation is to enhance understanding of the molecular mechanisms by which evolution has shaped the regulation of gene expression in a family of genes, like the RGM family.