Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/75236
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Type: Journal article
Title: An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution
Author: Williams, C.
Hoppe, H.
Rezgui, D.
Strickland, M.
Forbes, B.
Grutzner, F.
Frago, S.
Ellis, R.
Wattana-Amorn, P.
Prince, S.
Zaccheo, O.
Nolan, C.
Mungall, A.
Jones, E.
Crump, M.
Hassan, A.
Citation: Science, 2012; 338(6111):1209-1213
Publisher: Amer Assoc Advancement Science
Issue Date: 2012
ISSN: 0036-8075
1095-9203
Statement of
Responsibility: 
Christopher Williams, Hans-Jürgen Hoppe, Dellel Rezgui, Madeleine Strickland, Briony E. Forbes, Frank Grutzner, Susana Frago, Rosamund Z. Ellis, Pakorn Wattana-Amorn, Stuart N. Prince, Oliver J. Zaccheo, Catherine M. Nolan, Andrew J. Mungall, E. Yvonne Jones, Matthew P. Crump, A. Bassim Hassan
Abstract: 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.
Keywords: Animals; Humans; Insulin-Like Growth Factor II; Receptor, IGF Type 2; Evolution, Molecular; Phylogeny; Species Specificity; Genomic Imprinting; Alternative Splicing; Binding Sites; Amino Acid Sequence; Conserved Sequence; Protein Structure, Tertiary; Exons; Molecular Sequence Data; Enhancer Elements, Genetic
Rights: Copyright 2012 by the American Association for the Advancement of Science; all rights reserved.
RMID: 0020123305
DOI: 10.1126/science.1228633
Appears in Collections:Molecular and Biomedical Science publications
Environment Institute Leaders publications

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