Genomic analysis of immunity in a Urochordate and the emergence of the vertebrate immune system: "waiting for Godot"

Genomic analysis of immunity in a Urochordate and the emergence of the vertebrate immune system: "waiting for Godot"
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DOI:
10.1007/s00251-003-0606-5
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发表时间:
2003-11-01
期刊:
影响因子:
3.2
通讯作者:
Nonaka, M
Nonaka, M
中科院分区:
医学4区
文献类型:
--
作者:
Azumi, K;De Santis, R;Nonaka, M

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全基因组序列分析在无脊椎动物脊索动物,玻璃海鞘,提供了一个全面的图片免疫相关基因在生物体中,占据了脊椎动物进化的关键系统发育的位置。获得性免疫的关键基因,如主要组织相容性复合体(MHC)I类和II类基因,T细胞受体或二聚免疫球蛋白分子,尚未在玻璃海鞘基因组中确定。许多参与先天免疫的基因已经被鉴定,包括补体成分、Toll样受体和参与免疫应答的细胞内信号转导的基因,并且与脊椎动物相比显示出扩增和意想不到的多样性。此外,一些基因被确定为预测与细胞外C型凝集素或免疫球蛋白结构域和细胞内免疫受体酪氨酸为基础的抑制基序(ITIM)和免疫受体酪氨酸为基础的激活基序(ITAM)(加上其相关的信号转导分子),表明激活和抑制受体具有MHC独立的功能和早期进化起源的膜蛋白。脊椎动物获得性免疫的一个重要组成部分是体细胞多样性,而负责多样性产生的重组激活基因(RAG)和激活诱导的胞苷脱氨酶(AID)基因在玻璃海鞘中不存在。然而,有关键的V区,免疫球蛋白超家族VC1样核心的基本特征,以及分散在整个基因组中等待戈多的可能的原始MHC区域。
Genome-wide sequence analysis in the invertebrate chordate, Ciona intestinalis, has provided a comprehensive picture of immune-related genes in an organism that occupies a key phylogenetic position in vertebrate evolution. The pivotal genes for adaptive immunity, such as the major histocompatibility complex (MHC) class I and II genes, T-cell receptors, or dimeric immunoglobulin molecules, have not been identified in the Ciona genome. Many genes involved in innate immunity have been identified, including complement components, Toll-like receptors, and the genes involved in intracellular signal transduction of immune responses, and show both expansion and unexpected diversity in comparison with the vertebrates. In addition, a number of genes were identified which predicted integral membrane proteins with extracellular C-type lectin or immunoglobulin domains and intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and immunoreceptor tyrosine-based activation motifs (ITAMs) (plus their associated signal transduction molecules), suggesting that activating and inhibitory receptors have an MHC-independent function and an early evolutionary origin. A crucial component of vertebrate adaptive immunity is somatic diversification, and the recombination activating genes (RAG) and activation-induced cytidine deaminase (AID) genes responsible for the Generation of diversity are not present in Ciona. However, there are key V regions, the essential feature of an immunoglobulin superfamily VC1-like core, and possible proto-MHC regions scattered throughout the genome waiting for Godot.