TY - JOUR
T1 - An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution
AU - Williams, Christopher
AU - Hoppe, Hans-Jürgen
AU - Rezgui, Dellel
AU - Strickland, Madeleine
AU - Forbes, Briony
AU - Grutzner, Frank
AU - Fargo, Susana
AU - Ellis, Rosamund
AU - Wattana-Amorn, Pakorn
AU - Prince, Stuart
AU - Zaccheo, Oliver
AU - Nolan, Catherine
AU - Mungall, Andrew
AU - Jones, E
AU - Crump, Matthew
AU - Bassim Hassan, A
PY - 2012/11/30
Y1 - 2012/11/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84870181772&partnerID=8YFLogxK
U2 - 10.1126/science.1228633
DO - 10.1126/science.1228633
M3 - Article
VL - 338
SP - 1209
EP - 1213
JO - Science
JF - Science
SN - 1095-9203
IS - 6111
ER -