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Open Access Research article

Extensive expansion and diversification of the chemokine gene family in zebrafish: Identification of a novel chemokine subfamily CX

Hisayuki Nomiyama1*, Kunio Hieshima2, Naoki Osada3, Yoko Kato-Unoki4, Kaori Otsuka-Ono1, Sumio Takegawa2, Toshiaki Izawa5, Akio Yoshizawa5, Yutaka Kikuchi57, Sumio Tanase6, Retsu Miura1, Jun Kusuda3, Miki Nakao4 and Osamu Yoshie2

Author Affiliations

1 Department of Molecular Enzymology, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860-8556, Japan

2 Department of Microbiology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan

3 Department of Biomedical Resources, National Institute of Biomedical Innovation, Ibaraki, Osaka 567-0085, Japan

4 Laboratory of Marine Biochemistry, Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Science, Kyushu University, Fukuoka 812-8581, Japan

5 Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan

6 Department of Analytical Biochemistry, Kumamoto University School of Health Sciences, Kumamoto 862-0976, Japan

7 Department of Biological Science, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8526, Japan

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BMC Genomics 2008, 9:222  doi:10.1186/1471-2164-9-222

Published: 15 May 2008

Abstract

Background

The chemokine family plays important roles in cell migration and activation. In humans, at least 44 members are known. Based on the arrangement of the four conserved cysteine residues, chemokines are now classified into four subfamilies, CXC, CC, XC and CX3C. Given that zebrafish is an important experimental model and teleost fishes constitute an evolutionarily diverse group that forms half the vertebrate species, it would be useful to compare the zebrafish chemokine system with those of mammals. Prior to this study, however, only incomplete lists of the zebrafish chemokine genes were reported.

Results

We systematically searched chemokine genes in the zebrafish genome and EST databases, and identified more than 100 chemokine genes. These genes were CXC, CC and XC subfamily members, while no CX3C gene was identified. We also searched chemokine genes in pufferfish fugu and Tetraodon, and found only 18 chemokine genes in each species. The majority of the identified chemokine genes are unique to zebrafish or teleost fishes. However, several groups of chemokines are moderately similar to human chemokines, and some chemokines are orthologous to human homeostatic chemokines CXCL12 and CXCL14. Zebrafish also possesses a novel species-specific subfamily consisting of five members, which we term the CX subfamily. The CX chemokines lack one of the two N-terminus conserved cysteine residues but retain the third and the fourth ones. (Note that the XC subfamily only retains the second and fourth of the signature cysteines residues.) Phylogenetic analysis and genome organization of the chemokine genes showed that successive tandem duplication events generated the CX genes from the CC subfamily. Recombinant CXL-chr24a, one of the CX subfamily members on chromosome 24, showed marked chemotactic activity for carp leukocytes. The mRNA was expressed mainly during a certain period of the embryogenesis, suggesting its role in the zebrafish development.

Conclusion

The phylogenic and genomic organization analyses suggest that a substantial number of chemokine genes in zebrafish were generated by zebrafish-specific tandem duplication events. During such duplications, a novel chemokine subfamily termed CX was generated in zebrafish. Only two human chemokines CXCL12 and CXCL14 have the orthologous chemokines in zebrafish. The diversification observed in the numbers and sequences of chemokines in the fish may reflect the adaptation of the individual species to their respective biological environment.