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Human Molecular Genetics, 2001, Vol. 10, No. 17 1721-1728
© 2001 Oxford University Press

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

J. Keith Killian, Catherine M. Nolan1, Andrew A. Wylie, Tao Li2, Thanh H. Vu2, Andrew R. Hoffman2 and Randy L. Jirtle+

Departments of Radiation Oncology and Pathology, Duke University Medical Center, Durham, NC 27710, USA, 1Department of Zoology, University College Dublin, Ireland and 2Medical Service and GRECC, VA Palo Alto Health Care System and Department of Medicine, Stanford University School of Medicine, Palo Alto, CA 94304, USA

M6P/IGF2R imprinting first appeared approximately 150 million years ago following the divergence of prototherian from therian mammals. Although M6P/IGF2R is clearly imprinted in opossums and rodents, its imprint status in humans remains ambiguous. It is also still unknown if M6P/IGF2R imprinting was an ancestral mammalian epigenotype or if it evolved convergently. We report 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 parsimonious with a single ancestral origin of M6P/IGF2R imprinting followed by a lineage-specific disappearance of M6P/IGF2R imprinting in Euarchonta. The absence of M6P/IGF2R imprinting in extant primates, due to its disappearance from the primate lineage over 75 million years ago, demonstrates that imprinting at this locus does not predispose to human disease. Moreover, the divergent evolution of M6P/IGF2R imprinting predicts that the success of in vitro embryo procedures such as cloning may be species dependent.

+ To whom correspondence should be addressed at: Duke University Medical Center, Box 3433, Durham, NC 27710, USA. Tel: +1 919 684 2770; Fax: +1 919 684 5584; Email: jirtle@radonc.duke.edu


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