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Evolutionary origin of the complement system central to animal innate immunity

补体系统的进化起源对动物先天免疫至关重要

基本信息

批准号：
18370096
负责人：
NONAKA Masaru
金额：
$ 11.21万
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 (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18370096/
关键词：
Complement Evolution Cnidaria Gene duplication Lamprey 免疫学遣伝子遺伝子ネマトステラ

项目摘要

The complement system of mammals is a highly sophisticated and powerful body defense system composed of more than 30 serum and cell surface proteins. Its main function is to opsonize pathogens through covalent binding of the central component C3 using its unique intramolecular thioester bond. Most complement components show unique domain structures indicating that domain shuffling played an important role in establishing these components. In addition, there are many pairs of gene duplication products in the mammalian complement genes. To elucidate the evolutionary origin of the complement system, complement genes were searched from the recently analyzed cnidarian Nematostella vectensis genome. Two C3 (third complement component), two Bf (complement factor B) and one MASP (mannan-binding protein-associated serine protease) genes were identified. The entire protein-coding sequences of these cDNAs determined by RT-PCR and 5' and 3'RACE predicted a high degree of conservation of the primar … More y structure at the functionally important sites, suggesting that these complement components have been established and played a similar role as those of mammals, before the emergence of Bilateria. However, no complement genes have been identified in the D. melanogaster or C. elegans genomes, and the only complement gene reported thus far from protostome are the C3 and Bf genes of horseshoe crab. Moreover, our attempt to identify the C3 gene from Platyhelminthes, Sipuncula, Annelida and Mollusca failed, suggesting that the once established complement genes have been lost in most Protostome lineages. In contrast, complement genes have been identified from all deuterostomes analyzed thus far. However, liver EST analysis of lamprey showed that there were jawed vertebrate lineage- specific gene duplications of key component genes of the complement system. These gene duplications are believed to have played an important role in establishing the modern complement system of mammals, especially the classical pathway of activation. Less

哺乳动物的补体系统是一个高度复杂和强大的身体防御系统，由30多种血清和细胞表面蛋白质组成。其主要功能是利用其独特的分子内硫酯键，通过与中心成分C3的共价结合，对病原体进行调理。大多数补体成分具有独特的结构域结构，表明结构域洗牌在这些成分的形成中起着重要作用。此外，哺乳动物补体基因中存在许多对基因复制产物。为了阐明补体系统的进化起源，我们从最近分析的刺胞线虫基因组中寻找补体基因。鉴定出两个C3（第三补体成分）、两个Bf（补体因子B）和一个MASP（甘露聚糖结合蛋白相关丝氨酸蛋白酶）基因。通过RT-PCR和5′′和3′′race测定这些cdna的整个蛋白质编码序列，预测了重要功能位点的初级结构高度保守，表明这些补体成分在双侧虫出现之前就已经建立并发挥了与哺乳动物相似的作用。然而，在黑腹线虫和秀丽隐杆线虫的基因组中尚未发现补体基因，迄今为止报道的补体基因只有马蹄蟹的C3和Bf基因。此外，我们试图从圆角类动物、星形动物、环节动物和软体动物中鉴定C3基因的尝试失败了，这表明曾经建立的补体基因在大多数原石动物谱系中已经丢失。相比之下，补体基因已经从所有分析的后口动物鉴定到目前为止。然而，对七鳃鳗肝脏的EST分析表明，补体系统的关键组成基因存在颚脊椎动物谱系特异性基因重复。这些基因复制被认为在哺乳动物现代补体系统的建立，特别是经典的激活途径中发挥了重要作用。少