An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution

Christopher Williams; Hans-Jürgen Hoppe; Dellel Rezgui; Madeleine Strickland; Briony Forbes; Frank Grutzner; Susana Fargo; Rosamund Ellis; Pakorn Wattana-Amorn; Stuart Prince; Oliver Zaccheo; Catherine Nolan; Andrew Mungall; E Jones; Matthew Crump; A Bassim Hassan

doi:10.1126/science.1228633

An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution

Christopher Williams, Hans-Jürgen Hoppe, Dellel Rezgui, Madeleine Strickland, Briony Forbes, Frank Grutzner, Susana Fargo, Rosamund Ellis, Pakorn Wattana-Amorn, Stuart Prince, Oliver Zaccheo, Catherine Nolan, Andrew Mungall, E Jones, Matthew Crump, A Bassim Hassan

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1209-1213
Number of pages	5
Journal	Science
Volume	338
Issue number	6111
DOIs	https://doi.org/10.1126/science.1228633
Publication status	Published - 30 Nov 2012

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Williams, C., Hoppe, H-J., Rezgui, D., Strickland, M., Forbes, B., Grutzner, F., Fargo, S., Ellis, R., Wattana-Amorn, P., Prince, S., Zaccheo, O., Nolan, C., Mungall, A., Jones, E., Crump, M., & Bassim Hassan, A. (2012). An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution. Science, 338(6111), 1209-1213. https://doi.org/10.1126/science.1228633

Williams, Christopher ; Hoppe, Hans-Jürgen ; Rezgui, Dellel ; Strickland, Madeleine ; Forbes, Briony ; Grutzner, Frank ; Fargo, Susana ; Ellis, Rosamund ; Wattana-Amorn, Pakorn ; Prince, Stuart ; Zaccheo, Oliver ; Nolan, Catherine ; Mungall, Andrew ; Jones, E ; Crump, Matthew ; Bassim Hassan, A. / An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution. In: Science. 2012 ; Vol. 338, No. 6111. pp. 1209-1213.

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title = "An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution",

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.",

author = "Christopher Williams and Hans-J{\"u}rgen Hoppe and Dellel Rezgui and Madeleine Strickland and Briony Forbes and Frank Grutzner and Susana Fargo and Rosamund Ellis and Pakorn Wattana-Amorn and Stuart Prince and Oliver Zaccheo and Catherine Nolan and Andrew Mungall and E Jones and Matthew Crump and {Bassim Hassan}, A",

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month = nov,

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doi = "10.1126/science.1228633",

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Williams, C, Hoppe, H-J, Rezgui, D, Strickland, M, Forbes, B, Grutzner, F, Fargo, S, Ellis, R, Wattana-Amorn, P, Prince, S, Zaccheo, O, Nolan, C, Mungall, A, Jones, E, Crump, M & Bassim Hassan, A 2012, 'An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution', Science, vol. 338, no. 6111, pp. 1209-1213. https://doi.org/10.1126/science.1228633

An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution. / Williams, Christopher; Hoppe, Hans-Jürgen; Rezgui, Dellel; Strickland, Madeleine; Forbes, Briony; Grutzner, Frank; Fargo, Susana; Ellis, Rosamund; Wattana-Amorn, Pakorn; Prince, Stuart; Zaccheo, Oliver; Nolan, Catherine; Mungall, Andrew; Jones, E; Crump, Matthew; Bassim Hassan, A.

In: Science, Vol. 338, No. 6111, 30.11.2012, p. 1209-1213.

Research output: Contribution to journal › Article › peer-review

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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.

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JF - Science

SN - 1095-9203

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An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution

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