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The origin and evolution the complement system, a multi-component body defense mechanism

补体系统的起源和进化，一种多成分的机体防御机制

基本信息

批准号：
15207019
负责人：
NONAKA Masaru
金额：
$ 28.37万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15207019/
关键词：
complement evolution cnidaria C3 urochordate 膜傷害起源海綿動物棘胞動物

项目摘要

The evolutionary origin of the complement system was searched by RT-PCR using primers compatible with all known thioester protein genes encoding for the central component of the complement system, C3, and a serum protease inhibitor, alpha-2 macrogrobulin(A2M). From sea anemone (cnidaria), both the C3 and A2M genes were identified, whereas only the A2M gene was identified from hydra (cnidaria), snail (mollusca) and peanut worm (sipuncula). These results indicate that the emergence of the thioester genes and the gene duplication between C3 and A2M predated the divergence between cnidaria and bilateralia. Although A2M seems to be conserved by most bilateralia, C3 has been lost many times in the protostome lineage. Through the analysis of the complement system of sea squirt, the alpha and beta subunit genes of integrin-type complement receptor were cloned, and this receptor was shown to enhance phagocytosis through binding with activated C3. In addition, a possible linkage between the sea squirt C3 and Bf genes was tested by a chromosome-FISH analysis. They were detected on different chromosomes, excluding an ancient origin of the vertebrate MHC class III region. Through molecular cloning analysis of several shark species, the C3, C4 and C5 genes were identified, establishing that the C3/C4/C5 gene duplication predated the divergence of the cartilaginous fish. All these results suggested that the central part of the complement system was established more than 1000 million years ago, then most gene families merged in the common ancestor of deuterostomes, and finally the gene duplications which characterized the complement system of higher vertebrates occurred in the common ancestor of the jawed vertebrates.

使用与编码补体系统核心成分 C3 和血清蛋白酶抑制剂 α-2 巨球蛋白 (A2M) 的所有已知硫酯蛋白基因兼容的引物，通过 RT-PCR 搜索补体系统的进化起源。从海葵 (刺胞动物) 中，C3 和 A2M 基因均被鉴定出来，而从水螅 (刺胞动物)、蜗牛 (软体动物) 和花生虫 (sipuncula) 中仅鉴定出 A2M 基因。这些结果表明，硫酯基因的出现以及C3和A2M之间的基因复制早于刺胞动物和双侧动物之间的分化。尽管 A2M 似乎在大多数双侧动物中都是保守的，但 C3 在原口动物谱系中已经多次丢失。通过对海鞘补体系统的分析，克隆了整合素型补体受体的α和β亚基基因，该受体通过与活化的C3结合而增强吞噬作用。此外，还通过染色体 FISH 分析测试了海鞘 C3 和 Bf 基因之间可能存在的联系。它们在不同的染色体上被检测到，不包括脊椎动物 MHC III 类区域的古老起源。通过对几种鲨鱼的分子克隆分析，鉴定出 C3、C4 和 C5 基因，确定 C3/C4/C5 基因复制早于软骨鱼的分化。所有这些结果表明，补体系统的核心部分在10亿多年前就已经建立，然后大多数基因家族在后口动物的共同祖先中融合，最后，代表高等脊椎动物补体系统特征的基因复制发生在有颌脊椎动物的共同祖先中。