Identification of an interferon gamma homologue in Fugu, Takifugu rubripes.
Identification of an interferon gamma homologue in Fugu, Takifugu rubripes.
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DOI：
10.1016/j.fsi.2004.04.015
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发表时间：
2004-10
影响因子：
4.7
通讯作者：
J. Zou;Y. Yoshiura;J. M. Dijkstra;M. Sakai;M. Ototake;C. Secombes
中科院分区：
文献类型：
--
作者：
J. Zou;Y. Yoshiura;J. M. Dijkstra;M. Sakai;M. Ototake;C. Secombes
干扰素-g是调节细胞免疫反应的关键因子。它最初被认为是一种抗病毒因子，但也在激活巨噬细胞、通过I类和II类主要组织相容性复合体(MHC)分子刺激抗原呈递以及调节T细胞分化方面发挥关键作用[1]。干扰素-g已在许多哺乳动物物种中被鉴定出来，但迄今为止，鸟类是唯一一种使用表达克隆方法对干扰素-g基因进行测序的非哺乳动物物种[2，3]。最近完成了河豚全基因组的测序，为鉴定该物种中的细胞因子基因提供了强有力的工具。在过去的几年里，通过比较生物信息学方法分析其基因组数据库，在河豚中发现了许多细胞因子同源物，如IL-10[4]、IL-12[5]、IL-18[6]和I型干扰素[7]。许多研究表明，包括细胞因子基因在内的许多基因的染色体位置在河豚和人类之间是保守的(Synteny)，这有助于识别某些与哺乳动物同源性有限的细胞因子。例如，与IL-12相邻的基因的染色体排列与人类基因组相应区域的染色体排列相似[5]。已知的IL-20位于人类基因组中的IL-10位点，也与河豚或四齿河豚[7，8]在物理上连接在同一支架上。利用这种所谓的共性比较分析方法，我们在这里描述了在河豚基因组数据库中发现了一个类似干扰素-g的分子，这是鱼类中第一个这样的基因。干扰素-g是一个单拷贝基因，定位于人类染色体12q14和小鼠染色体10[9]。基因同源性的比较分析表明，干扰素-g周围的基因，如小鼠核蛋白双分钟1(MDM1)的同源基因和双特异性酪氨酸磷酸化调控基因
Interferon gamma (IFN-g) is a key player regulating cell mediated immune responses. It was originally identified as an antiviral factor but also has crucial roles in activation of macrophages, stimulation of antigen presentation through class I and class II major histocompatibility complex (MHC) molecules, and regulation of T cell differentiation [1]. IFN-g has been identified in many mammalian species but to date birds are the only non-mammal species whose IFN-g gene has been sequenced, using an expression cloning method [2, 3].The drafted sequence of the whole Fugu genome has recently been completed and provides a powerful tool to identify cytokine genes in this species. In the last couple of years, many cytokine homologues such as IL-10 [4], IL-12 [5], IL-18 [6], and type I interferon [7], have been found in Fugu by analysing its genome database using comparative bioinformatics approaches. It has been demonstrated in a number of studies that chromosomal location of many genes, including cytokine genes, is conserved between Fugu and humans (synteny), which is useful for identifying certain cytokines with limited homology to their mammalian counterparts. For example, the chromosomal arrangements of the genes adjacent to IL-12 are comparable to those in the corresponding region in the human genome [5]. IL-20 known to be located in the IL-10 locus in the human genome, is also physically linked in the same scaffold with Fugu or tetraodon IL-10 [7, 8]. Using this so-called synteny comparative analysis approach, we describe here the discovery of an IFN-g like molecule in the Fugu genome database, the first such gene in a fish species. IFN-g is a single copy gene mapped to chromosome 12q14 in human and chromosome 10 in mouse [9]. Comparative analysis of the gene synteny reveals that genes surrounding IFN-g such as a homologue to mouse nuclear protein double minute 1 (MDM1) and dual-specificity tyrosine phosphorylation-regulated