Evolution and Regulation of Imprinted Genes

Randy Jirtle
Department of Radiation Oncology; Duke University Medical Center

Genomic imprinting is an epigenetic form of gene regulation that results in parent-of-origin dependent expression. Imprinting at both the M6P/IGF2R and IGF2 loci evolved approximately 150 million years ago in an ancestor common to marsupials and eutherian mammals, demonstrating that invasive placentation and gestational fetal growth are not required for the evolution of imprinting (Killian et al. Mol. Cell 5: 707-716, 2000). Furthermore, the opossum lacks the intronic structures thought to be necessary for M6P/IGF2R imprinting in mice. Marsupials therefore either developed an alternative imprinting system or they share an imprinting mechanism with eutherians whose fundamental features are yet to be discovered. We have also recently identify two reciprocally imprinted genes, DLK1 and GTL2, which together define a novel imprinted domain on human chromosome 14q32 with structural and putative regulatory features highly analogous to those implicated in IGF2/H19 imprint regulation (Wylie et al. Genome Res. 10: 1711-1718, 2000). These results provide the first evidence that a common mechanism and domain organization may be used for juxtapositioned reciprocally imprinted genes. (Supported by the NIH grants CA25951 and ES08823, DOD grant DAMD17-98-1-8305, Sumitomo Chemical Company and AstraZeneca Pharmaceuticals)