Chemokine PARC gene (SCYA18) generated by fusion of two MIP-1alpha/LD78alpha-like genes.
Two loci in the human genome, chromosomes 4q12-q21 and 17q11.2, contain clusters of CXC and CC chemokine subfamily genes, respectively. Since mice appear to contain fewer chemokine genes than humans, numerous gene duplications might have occurred in each locus of the human genome. Here we describe the genomic organization of the human pulmonary and activation-regulated CC chemokine (PARC), also known as DC-CK1 and AMAC-1. Despite high sequence similarity to a CC chemokine macrophage inflammatory protein-1alpha (MIP-1alpha)/LD78alpha, PARC is chemotactic for lymphocytes and not for monocytes and does not share its receptor with MIP-1alpha. Analyses of the BAC clones containing the human PARC gene indicated that the gene is located most closely to MIP-1alpha (HGMW-approved symbol SCYA3) and MIP-1beta (HGMW-approved symbol SCYA4) on chromosome 17q11.2. Dot-plot comparison suggested that the PARC gene had been generated by fusion of two MIP-1alpha-like genes with deletion and selective usage of exons. Base changes accumulated before and after the fusion might have adapted the gene to a new function. Since there are variably duplicated copies of the MIP-1alpha gene called LD78beta (HGMW-approved symbol SCYA3L) in the vicinity of the MIP-1alpha gene, the locus surrounding the MIP-1alpha gene seems to be a "hot spring" that continuously produces new family genes. This evidence provides a new model, duplication and fusion, of the molecular basis for diversity within a gene family.
Department of Biochemistry, Kumamoto University Medical School, Honjo, Japan.
Y
Y
Tasaki
S
S
Fukuda
M
M
Iio
R
R
Miura
T
T
Imai
S
S
Sugano
O
O
Yoshie
A L
AL
Hughes
H
H
Nomiyama
D000818:Animals; D001483:Base Sequence; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000235:genetics*; D019742:Chemokines, CC / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000235:genetics*; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid
C111792:CCL18 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D011993:Recombinant Fusion Proteins