Molecular evolution of the human interleukin–8 receptor gene cluster

lnterleukin–8 (IL–8) is the prototype for a family of at least eight neutrophil chemoattractants whose genes map to human chromosome 4q13–q21. Two human IL–8 receptors, IL8RA and IL8RB, are known from cDNA cloning; IL8RA is a promiscuous receptor for at least two other related ligands, GROα and NAP–2. We now report cloning of the genes for IL8RA, IL8RB and a recently inactivated pseudogene of receptor A (IL8RAP). These form a cluster of only three genes in the superfamily of G protein–coupled receptors (GPCRs) and map to 2q34–q35. The revolutionary diversity displayed by the IL–8 ligand–receptor complex — ligand promiscuity for IL–8, receptor promiscuity for IL8RA, gene duplication for both ligands and receptors and gene extinction in the case of IL8RAP — is unprecedented for the GPCR superfamily.