Comprehensive clarification of two paralogous interleukin 4/13 loci in teleost fish
Comprehensive clarification of two paralogous interleukin 4/13 loci in teleost fish
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DOI：
10.1007/s00251-008-0299-x
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发表时间：
2008-07-01
期刊：
影响因子：
3.2
通讯作者：
Dijkstra, Johannes Martinus
中科院分区：
文献类型：
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作者：
Ohtani, Maki;Hayashi, Nobuhiro;Dijkstra, Johannes Martinus
白细胞介素4和13 （IL-4和IL-13）是人类5号染色体上邻近基因编码的与Th2免疫应答相关的细胞因子。此前，人们曾努力在鱼类中检测这些基因，但由于缺乏序列保护，研究受到了阻碍。Li等人（Mol Immunol, 44:2078-2086, 2007）将一种绿斑河豚（Tetraodon nigrovirides）基因注释为IL-4，但该注释没有得到很好的证实。然而，目前的研究得出结论，报道的河豚基因确实属于IL-4/13谱系，同时也描述了在同源基因组区域中额外的IL-4/13拷贝。我们对鱼类中IL-4/13位点的分析描述了(1)基因组区域历史，(2)特有的内含子-外显子组织，(3)推断出几种硬骨鱼物种的IL-4/13分子，(4)IL-4/13谱系特异性蛋白基元，包括半胱氨酸对（1对），(5)计算机软件预测I型细胞因子折叠。硬骨鱼的IL-4/13分子有额外的半胱氨酸对（2对）或残余物，这在哺乳动物的IL-4和IL-13中是不存在的。我们无法确定硬骨鱼的IL-4/13基因是否与IL-4或IL-13同源，或者这些哺乳动物基因是否在进化后期分离。
Interleukins 4 and 13 (IL-4 and IL-13) are related cytokines important for Th2 immune responses and encoded by adjacent genes on human chromosome 5. Efforts were made previously to detect these genes in fish, but research was hampered by a lack of sequence conservation. A Tetraodon nigrovirides (green spotted pufferfish) gene was annotated as IL-4 by Li et al. (Mol Immunol, 44:2078-2086, 2007), but this annotation was not well substantiated. However, the present study concludes that the reported pufferfish gene belongs to the IL-4/13 lineage indeed, while also describing an additional IL-4/13 copy in a paralogous genomic region. Our analyses of IL-4/13 loci in fish describe (1) genomic region history, (2) characteristic intron-exon organization, (3) deduced IL-4/13 molecules for several teleost fish species, (4) IL-4/13 lineage-specific protein motifs including a cysteine pair (pair 1), and (5) computer software predictions of a type I cytokine fold. Teleost IL-4/13 molecules have an additional cysteine pair (pair 2) or remnants thereof, which is absent in mammalian IL-4 and IL-13. We were unable to determine if the teleost IL-4/13 genes are orthologous to either IL-4 or IL-13, or if these mammalian genes separated later in evolution.