Divergent evolution in M6P/IGF2R imprinting from the Jurassic to the Quaternary

M6P/IGF2R imprinting first appeared approximately 150 million years ago fol lowing the divergence of prototherian from therian mammals. Although M6P/IG F2R is clearly imprinted in opossums and rodents, its imprint status in hum ans remains ambiguous. It is also still unknown if M6P/IGF2R imprinting was an ancestral mammalian epigenotype or if it evolved convergently. We repor t herein that M6P/IGF2R is imprinted in Artiodactyla, as it is in Rodentia and Marsupialia, but that it is not imprinted in Scandentia, Dermoptera and Primates, including ringtail lemurs and humans. These results are most par simonious with a single ancestral origin of M6P/IGF2R imprinting followed b y a lineage-specific disappearance of M6P/IGF2R imprinting in Euarchonta. T he absence of M6P/IGF2R imprinting in extant primates, due to its disappear ance from the primate lineage over 75 million years ago, demonstrates that imprinting at this locus does not predispose to human disease. Moreover, th e divergent evolution of M6P/IGF2R imprinting predicts that the success of in vitro embryo procedures such as cloning may be species dependent.