IGF2 (insulin-like growth factor 2) and M6P/IGF2R (mannose 6-phosphate/insu
lin-like growth factor 2 receptor) are imprinted in marsupials and eutheria
ns but not in birds. These results along with the absence of M6P/IGF2R impr
inting in the egg-laying monotremes indicate that the parental imprinting o
f fetal growth-regulatory genes may be unique to viviparous mammals. In thi
s investigation, we have cloned IGF2 from two monotreme mammals, the platyp
us and echidna, to further investigate the origin of imprinting. We report
herein that like M6P/IGF2R, IGF2 is not imprinted in monotremes. Thus, alth
ough IGF2 encodes for a highly conserved growth factor in chordates, it is
only imprinted in therian mammals. These findings support a concurrent orig
in of IGF2 and M6P/IGF2R imprinting in the late Jurassic/early Cretaceous p
eriod. The absence of imprinting in monotremes, despite apparent interparen
tal conflicts over maternal-offspring exchange, argues that a fortuitous co
ngruency of genetic and epigenetic events may have limited the phylogenetic
breadth of genomic imprinting to therian mammals. (C) 2001 Wiley-Liss, Inc
.