Coevolution of the mammalian chemokines and their receptors

A phylogeny of mammalian chemokines revealed two major clusters, correspond ing to the CC and CXC chemokines; the C chemokines appeared to be more clos ely related to the former. In a phylogeny of chemokine receptors, there wer e also two major clusters: one containing CC chemokine receptors plus other receptors of unknown function and another containing CXC receptors and oth er receptors of unknown function. However, within the CC receptors, there w as not a close correspondence between the phylogenies of chemokines and the ir receptors. The CC chemokines contained two major subfamilies: (1) the MI P subfamily (including MIP-l alpha, MIP-1 beta, and RANTES); and (2) the MC P subfamily (including MCP-1,-2,-3, and -4 and eotaxin). Receptors having p referred ligands in the MCP subfamily did not constitute a monophyletic gro up but rather evolved twice independently. Reconstruction of ancestral amin o acid sequences suggested that these two groups of MCP receptors did not c onvergently evolve any amino acid residues; rather, they convergently lost sequence features found in the third and fourth extracellular domains of kn own receptors for MIP-subfamily chemokines.