An unusual mode of concerted evolution of the EGF-TM7 receptor chimera EMR2.
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
Mark J
MJ
Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
Matmati
Mourad
M
Madsen
Ole
O
Pouwels
Walter
W
Wang
YongYi
Y
Bontrop
Ronald E
RE
Heidt
Peter J
PJ
Hoek
Robert M
RM
Hamann
Jörg
J
D000595:Amino Acid Sequence; D000818:Animals; D002144:Callithrix; D004285:Dogs; D019143:Evolution, Molecular; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D048529:Papio hamadryas; D011148:Pongo pygmaeus; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics*; D012452:Saguinus
D043562:Receptors, G-Protein-Coupled