MOLECULAR EVOLUTION OF THE N-FORMYL PEPTIDE AND C5A RECEPTORS IN NONHUMAN-PRIMATES

N-formyl peptides (FMLP) and complement fragment C5a are neutrophil ch emoattractants. In humans, a single-copy gene was identified for the C 5a receptor, and the receptor for FMLP (FPR1) is encoded by a single g ene that shows 53% amino acid similarity to the C5aR. Two other human FPR1 homologues, FPR-like 1 (FPR2/FPRL1) and FPR-like 2 (FPRL2) have b een cloned. The human C5aR, FPR1, FPRL1, and FPRL2 are physically link ed. By direct sequencing or by sequencing plasmid clones we studied th e C5aR and FPR genes from four non-human primates (chimpanzee, gorilla , orangutan, and macaque). The sequences showed 95%-99% similarity to the human homologues, with the major divergences observed in macaque. In these genes, the transmembrane and the cytoplasmic domains are high ly conserved, while the highest divergence corresponded to the extrace llular loops involved in ligand binding. Additionally, we constructed a physical map of these genes in non-human primates. In all species th e four genes were physically linked and we defined the relative orient ation of the four genes in primates: C5aR > FPR1 > FPR2 (FPRL1) > FPRL 2.