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

Abstract

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.

Biparental expression of ESX1L gene in placentas from normal and intrauterine growth-restricted pregnancies

“…Nevertheless, gene sequencing and protein analysis are necessary to draw the conclusion that the ESX1L gene is not involved in IUGR. Discrepancy of the imprinting status of loci between humans and mice has already been reported for Igf2R/IGF2R; in an extensive study of seven placentas, 46 conceptuses and seven Wilm's tumors, Killian et al 35 found no evidence of imprinting of IGF2R in humans.…”

Putative imprinted gene expression in uniparental bovine embryo models

“…Second, it may be that bovine genes are not imprinted, not completely imprinted ('leaky' expression) or show tissuespecific temporal imprinting in adult tissues. IGF2R has been found previously to be imprinted in the mouse and cow (Killian et al 2001), but not in the human Yang et al 2003). There are also numerous genes that show imprinting in only a select number of tissues, such as PPP1R9A, which is maternally expressed in fetal muscle, eye and placenta but is biallelically expressed in other tissues (Nakabayashi et al 2004), OBPH1, which shows predominant maternal expression in the placenta but biallelic expression in fetal and newborn organs in the human and mouse (Higashimoto et al 2002), and KCNQ1, whose expression is imprinted in several tissues but not in the heart (Lee et al 1997).…”

Long-range DNase I hypersensitivity mapping reveals the imprinted Igf2r and Air promoters share cis-regulatory elements

“…The discordance in the Igf2r/Air region may reflect the lack of conservation of genomic imprinting between the mouse and human Igf2r genes. The human IGF2R gene shows a polymorphic type of imprinted expression that is limited to embryonic stages, whereas adult tissues have been reported to show only biparental expression (Xu et al 1993;Killian et al 2001). This contrasts to the maintenance of imprinted Igf2r expression in most tissues of the mouse embryo and adult (Braidotti et al 2004).…”

“…Because of the lack of conservation of imprinted expression between the mouse and human Igf2r genes (Xu et al 1993;Killian et al 2001), we used an unbiased approach to map candidate transcriptional regulators in the mouse Igf2r/Air region using DHS assays. DHS assays identify short regions of approximately 200-400 bp that are sensitive to the action of nucleases because of nucleosome displacement or altered chromatin structure.…”