Extensive expansion and diversification of the chemokine gene family in zebrafish: identification of a novel chemokine subfamily CX.
Extensive expansion and diversification of the chemokine gene family in zebrafish: identification of a novel chemokine subfamily CX.
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DOI：
10.1186/1471-2164-9-222
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发表时间：
2008-05-15
期刊：
影响因子：
4.4
通讯作者：
Yoshie O
中科院分区：
文献类型：
--
作者：
Nomiyama H;Hieshima K;Osada N;Kato-Unoki Y;Otsuka-Ono K;Takegawa S;Izawa T;Yoshizawa A;Kikuchi Y;Tanase S;Miura R;Kusuda J;Nakao M;Yoshie O
趋化因子家族在细胞迁移和活化中起重要作用。在人类中，至少有44个已知成员。基于四个保守的半胱氨酸残基的排列，趋化因子现在被分为四个亚家族，CXC，CC，XC和CX3C。考虑到斑马鱼是一个重要的实验模型，硬骨鱼构成了一个进化上多样化的群体，形成了一半的脊椎动物物种，这将是有用的比较斑马鱼的趋化因子系统与哺乳动物。然而，在这项研究之前，只有斑马鱼趋化因子基因的不完整列表被报道。我们在斑马鱼基因组和EST数据库中系统地搜索了趋化因子基因，并鉴定了100多个趋化因子基因。这些基因是CXC、CC和XC亚家族成员，而未鉴定到CX3C基因。我们还在河豚和河豚中搜索了趋化因子基因，发现每个物种中只有18个趋化因子基因。大多数已鉴定的趋化因子基因是斑马鱼或硬骨鱼所特有的。然而，几组趋化因子与人趋化因子适度相似，并且一些趋化因子与人稳态趋化因子CXCL 12和CXCL 14是正交的。斑马鱼还拥有一个新的物种特异性亚家族，由五个成员组成，我们称之为CX亚家族。CX趋化因子缺乏两个N-末端保守的半胱氨酸残基之一，但保留第三和第四个。(Note XC亚家族仅保留第二个和第四个标志性半胱氨酸残基。系统发育分析和基因组组织的趋化因子基因表明，连续的串联重复事件产生的CX基因从CC亚家族。重组CXL-chr24a基因是位于24号染色体上的CX亚家族成员之一，对鲤鱼白细胞具有明显的趋化活性。该基因主要在胚胎发育的某个时期表达，提示其在斑马鱼发育中的作用。基因组学和基因组结构分析表明，斑马鱼中大量的趋化因子基因是由斑马鱼特异性串联重复事件产生的。在这种复制过程中，在斑马鱼中产生了一种新的称为CX的趋化因子亚家族。只有两种人类趋化因子CXCL12和CXCL14具有斑马鱼中的正向趋化因子。鱼类趋化因子的数量和序列的多样性可能反映了个体物种对各自生物环境的适应。
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. 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. 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.
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