Jin Hong-Jian, Shao Jian-Zhong, Xiang Li-Xin, Wang Hao, Sun Li-Li
College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
Mol Immunol. 2008 Mar;45(5):1258-68. doi: 10.1016/j.molimm.2007.09.015. Epub 2007 Oct 29.
The suppressors of cytokine signaling (SOCS) family play important roles in regulating a variety of signal transduction pathways that are involved in immunity, growth and development of organisms. However, the family members in early vertebrate species and their evolutionary history and relationships remain largely unknown. In present study, totally 120 SOCS genes from various species were globally investigated, among of which 66 new SOCS genes were identified, including 55 SOCS genes from five fish species, Tetraodon nigroviridis, Danio rerio, Takifugu rubripes, Gasterosteus aculeatus and Oryzias latipes, 11 from amphibian, avian and insects. The results showed that fish possess at least 12 SOCS family members, including eight known mammalian SOCS members (CISH, SOCS-1-7) and four novel members (SOCS-3b, -5b, -8 and -9). Fish SOCS proteins share strikingly high levels of sequence similarity in SH2 domain and SOCS box region with higher vertebrate counterparts, and the organization of SOCS genes are conserved during vertebrate SOCS evolution. The expression levels of the most fish SOCS genes, such as CISH, SOCS-1-5 and SOCS-9, were increased after LPS challenge, indicating that they are involved in inflammatory response. Phylogenetic analyses clearly showed that the SOCS gene family could be divided into two subfamilies (named as types I and II subfamily). Type I subfamily consists of vertebrate SOCS-4-7, SOCS-5b, SOCS-9 and all invertebrate SOCS genes. Type II subfamily contains vertebrate CISH, SOCS-1-3, SOCS-3b and SOCS-8. Only SOCS-5, -6 and -7 like genes existed in invertebrate, which may be generated by twice-ancient duplication events. Type II subfamily members were likely derived from a certain type I member by gene duplication in the vertebrate lineages after the divergence of vertebrate from invertebrate. In type II subfamily, SOCS genes formed two separate monophyletic groups, respectively, which suggests that another duplication event occurred in the early stage of evolution. The fact that SOCS-9, SOCS-5b, SOCS-3b and SOCS-8 present only in teleostei suggests that even more duplication events occurred before teleostei and higher vertebrates diverged. Results suggest that the SOCS multi-gene family derived from the expansion of an ancestral SOCS gene through at least cubical duplication events during evolution process.
细胞因子信号转导抑制因子（SOCS）家族在调节多种信号转导途径中发挥重要作用，这些信号转导途径涉及生物体的免疫、生长和发育。然而，早期脊椎动物物种中的家族成员及其进化历史和关系在很大程度上仍然未知。在本研究中，对来自不同物种的总共120个SOCS基因进行了全面研究，其中鉴定出66个新的SOCS基因，包括来自5种鱼类（黑青斑河豚、斑马鱼、红鳍东方鲀、三刺鱼和青鳉）的55个SOCS基因，以及来自两栖动物、鸟类和昆虫的11个。结果表明，鱼类至少拥有12个SOCS家族成员，包括8个已知的哺乳动物SOCS成员（CISH、SOCS-1-7）和4个新成员（SOCS-3b、-5b、-8和-9）。鱼类SOCS蛋白在SH2结构域和SOCS框区域与高等脊椎动物对应物具有惊人的高度序列相似性，并且SOCS基因的组织在脊椎动物SOCS进化过程中是保守的。大多数鱼类SOCS基因，如CISH、SOCS-1-5和SOCS-9，在LPS刺激后表达水平升高，表明它们参与炎症反应。系统发育分析清楚地表明，SOCS基因家族可分为两个亚家族（命名为I型和II型亚家族）。I型亚家族由脊椎动物的SOCS-4-7、SOCS-5b、SOCS-9和所有无脊椎动物SOCS基因组成。II型亚家族包含脊椎动物的CISH、SOCS-1-3、SOCS-3b和SOCS-8。无脊椎动物中仅存在SOCS-5、-6和-7样基因，这可能是由两次古老的复制事件产生的。II型亚家族成员可能是在脊椎动物与无脊椎动物分化后，通过脊椎动物谱系中的基因复制从某个I型成员衍生而来。在II型亚家族中，SOCS基因分别形成两个独立的单系类群，这表明在进化早期发生了另一次复制事件。SOCS-9、SOCS-5b、SOCS-3b和SOCS-8仅存在于硬骨鱼中的事实表明，在硬骨鱼和高等脊椎动物分化之前发生了更多的复制事件。结果表明，SOCS多基因家族是在进化过程中通过至少三次复制事件从一个祖先SOCS基因扩展而来的。
