Isolation of novel GRO genes and a phylogenetic analysis of the CXC chemokine subfamily in mammals

Approximately 15 different alpha, or CXC, chemokines have thus far been iso lated from 11 species of mammals. Among the best studied chemokines are the 12 human proteins that are encoded by 11 paralogous genes. In order to bet ter understand the evolution and function of this group of genes, we isolat ed and characterized six novel GRO and GRO-related cDNA sequences from the cow (Bos taurus), the sheep (Ovis aries), the rabbit (Oryctolagus cuniculus ), and the guinea pig (Cavia porcellus). The amino acid sequence of the div erged guinea pig GRO or KC gene is only 50%-60% similar to presumed ortholo gs from other species, while the sheep and cow GRO proteins are 90%-99% sim ilar to each other. The presence of multiple GRO genes in the cow, the rabb it, and the sheep is consistent with what has been observed for humans. Phy logenetic analyses of amino acid sequences from 44 proteins indicate that g enes orthologous to many of the 11 known from humans exist in other species . One such gene, interleukin 8, or IL8, has been isolated from nine species , including the rodent guinea pie; however, this gene is absent in the rat and the mouser indicating a unique gene loss event in the rat/mouse (muroid rodent) lineage. The KC (or MIP2) gene of rodents appears to be orthologou s to the GRO gene found in other taxonomic orders. Combined evidence from d ifferent sources suggests that IP10 and MIG share sister taxon relationship s on the evolutionary tree, while the remaining paralogous genes represent independent lineages, with limited evidence for kinship between them. This observation indicates that these genes originated nearly contemporaneously via a series of gene duplication events. Relative-rate tests for synonymous and nonsynonymous nucleotide substitutions in the KC and IL8 genes did not detect rate heterogeneity; however, there are several notable features reg arding the ILS genes. For example, the IL8 proteins from two Old World monk eys are as similar to one another as they are to the IL8 protein from human s, and all observed nucleotide differences between the IL8 genes of the two monkeys cause amino acid changes, in other words, there are no synonymous differences between them.