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尾索动物免疫的基因组分析与脊椎动物免疫系统的出现:“等待戈多”

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

作者信息

Azumi Kaoru, De Santis Rosaria, De Tomaso Anthony, Rigoutsos Isidore, Yoshizaki Fumiko, Pinto Maria Rosaria, Marino Rita, Shida Kazuhito, Ikeda Makoto, Ikeda Masami, Arai Masafumi, Inoue Yasuhito, Shimizu Toshio, Satoh Nori, Rokhsar Daniel S, Du Pasquier Louis, Kasahara Masanori, Satake Masanobu, Nonaka Masaru

机构信息

Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.

出版信息

Immunogenetics. 2003 Nov;55(8):570-81. doi: 10.1007/s00251-003-0606-5. Epub 2003 Oct 7.

DOI:10.1007/s00251-003-0606-5
PMID:14530883
Abstract

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.

摘要

对无脊椎动物脊索动物海鞘进行的全基因组序列分析,为一种在脊椎动物进化中占据关键系统发育位置的生物体中的免疫相关基因提供了全面的图景。在海鞘基因组中尚未鉴定出适应性免疫的关键基因,如主要组织相容性复合体(MHC)I类和II类基因、T细胞受体或二聚体免疫球蛋白分子。已经鉴定出许多参与固有免疫的基因,包括补体成分、Toll样受体以及参与免疫反应细胞内信号转导的基因,与脊椎动物相比,这些基因呈现出扩增和意外的多样性。此外,还鉴定出了一些基因,这些基因预测的整合膜蛋白具有细胞外C型凝集素或免疫球蛋白结构域以及细胞内基于免疫受体酪氨酸的抑制基序(ITIMs)和基于免疫受体酪氨酸的激活基序(ITAMs)(以及它们相关的信号转导分子),这表明激活和抑制受体具有不依赖MHC的功能和早期进化起源。脊椎动物适应性免疫的一个关键组成部分是体细胞多样化,而负责产生多样性的重组激活基因(RAG)和激活诱导的胞苷脱氨酶(AID)基因在海鞘中并不存在。然而,在整个基因组中存在关键的V区域,这是免疫球蛋白超家族VC1样核心的基本特征,以及可能的原MHC区域,它们都有待进一步研究。

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