It has been proposed that proteins which are involved in host defence and susceptibility undergo accelerated evolution. Chemokine receptors have roles as pro-inflammatory agents acting in response to infection, and in addition are receptors for entry of viruses and other pathogens into cells. Consistent with this, their rate of evolution is higher than that for other members of the seven-transmembrane domain receptor family. The pattern of evolution of the chemokine receptors was examined in detail. Both chromosomal clusters of chemokine receptors (CC and CXC) showed evidence of a number of gene conversions. These are likely to have resulted in protein sequence changes, which could possibly alter function. 45% of a control group of clustered genes also showed evidence of conversion. Thus, the fixation of a gene conversion is not in itself sufficiently unusual in tandemly repeated genes and cannot be taken as strong evidence of a selection for a novel function. However, the degree of amino acid difference between the chemokine receptors CCR1 and CCR3 was greater than that for any of the control genes. Such changes could have functional implications for inter-species differences in chemokine receptor interactions with pathogens.
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