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Placental development and genomic imprinting coevolved with parental conflict over resource distribution to mammalian offspring. The imprinted genes IGF2 and IGF2R code for the growth promoter insulin-like growth factor 2 (IGF2) and its inhibitor, mannose 6-phosphate (M6P)/IGF2 receptor (IGF2R), respectively. M6P/IGF2R of birds and fish do not recognize IGF2. In monotremes, which lack imprinting, IGF2 specifically bound M6P/IGF2R via a hydrophobic CD loop. We show that the DNA coding the CD loop in monotremes functions as an exon splice enhancer (ESE) and that structural evolution of binding site loops (AB, HI, FG) improved therian IGF2 affinity. We propose that ESE evolution led to the fortuitous acquisition of IGF2 binding by M6P/IGF2R that drew IGF2R into parental conflict; subsequent imprinting may then have accelerated affinity maturation.

Original publication

DOI

10.1126/science.1228633

Type

Journal article

Journal

Science

Publication Date

30/11/2012

Volume

338

Pages

1209 - 1213

Keywords

Alternative Splicing, Amino Acid Sequence, Animals, Binding Sites, Conserved Sequence, Enhancer Elements, Genetic, Evolution, Molecular, Exons, Genomic Imprinting, Humans, Insulin-Like Growth Factor II, Molecular Sequence Data, Phylogeny, Protein Structure, Tertiary, Receptor, IGF Type 2, Species Specificity