Molecular Biology and Evolution, Vol 16, 180-193, Copyright © 1999 by Society for Molecular Biology and Evolution
WS Modi and T Yoshimura
Approximately 15 different alpha, or CXC, chemokines have thus far been
isolated 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
better understand the evolution and function of this group of genes, we
isolated 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 diverged guinea pig GRO or KC gene is only 50%-60% similar to
presumed orthologs from other species, while the sheep and cow GRO proteins
are 90%-99% similar to each other. The presence of multiple GRO genes in
the cow, the rabbit, and the sheep is consistent with what has been
observed for humans. Phylogenetic analyses of amino acid sequences from 44
proteins indicate that genes 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 pig; however,
this gene is absent in the rat and the mouse, indicating a unique gene loss
event in the rat/mouse (muroid rodent) lineage. The KC (or MIP2) gene of
rodents appears to be orthologous to the GRO gene found in other taxonomic
orders. Combined evidence from different sources suggests that IP10 and MIG
share sister taxon relationships 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 regarding the IL8 genes. For
example, the IL8 proteins from two Old World monkeys are as similar to one
another as they are to the IL8 protein from humans, 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.
ORIGINAL ARTICLE
Isolation of novel GRO genes and a phylogenetic analysis of the CXC chemokine subfamily in mammals
Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. modi@ncifcrf.gov
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