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An unusual mode of concerted evolution of the EGF‐TM7 receptor chimera EMR2
Author(s) -
Kwakkenbos Mark J.,
Matmati Mourad,
Madsen Ole,
Pouwels Walter,
Wang YongYi,
Bontrop Ronald E.,
Heidt Peter J.,
Hoek Robert M.,
Hamann Jörg
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-6500fje
Subject(s) - receptor , epidermal growth factor , biology , alternative splicing , extracellular , transmembrane protein , transmembrane domain , chimera (genetics) , microbiology and biotechnology , gene , rna splicing , genetics , messenger rna , rna
The epidermal growth factor (EGF)‐ TM7 receptors CD97, EMR1, EMR2, EMR3, and EMR4 form a group of adhesion class heptahelical molecules predominantly expressed by cells of the immune system. These receptors bind cellular ligands through EGF‐like domains, localized N‐terminal to a large extracellular region. Remarkably, EMR2 possesses a chimeric structure with a seven‐span transmembrane (TM7) region most related to EMR3 and an EGF domain region nearly identical to CD97. By comparing EGF‐TM7 receptors in primates and dogs, we identified an intriguing pattern of concerted evolution, apparently mediated by gene conversion, among EMR2 and the oppositely orientated and physically adjacent genes CD97 and EMR3. This concerted evolution has continuously maintained the chimeric structure of EMR2 since early mammal radiation. Most highly conserved between EMR2 and CD97 is the fourth EGF domain, which mediates binding to chondroitin sulfate, a ligand specificity shared by both receptors. Another ligand, CD55, is bound effectively only by CD97. We show that different molecular mechanisms (mutations vs. alternative splicing) prevent CD55 binding by EMR2 in hominoids. Our findings illustrate how various and partially opposing evolutionary events have shaped the structure and ligand specificity of a modern mammalian gene family.—Kwakkenbos, M. J., Matmati, M., Madsen, O., Pouwels, W., Wang, Y. Y., Bontrop, R. E., Heidt, P. J., Hoek, R. M., Hamann, J. An unusual mode of concerted evolution of the EGF‐TM7 receptor chimera EMR2. FASEB J. 20, E2026–E2035 (2006)