Adapting to a changing world: RAG genomics and evolution.
Adapting to a changing world: RAG genomics and evolution.
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DOI：
10.1186/1479-7364-2-2-132
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发表时间：
2005-06
期刊：
影响因子：
4.5
通讯作者：
Nahum LA
中科院分区：
文献类型：
--
作者：
Camargo MM;Nahum LA
重组激活基因(RAG)的起源被认为是适应性免疫的基础标志，其特征是存在能够识别和响应特定多肽抗原的抗原受体基因。在脊椎动物中，通过RAG-1和RAG-2蛋白复合体进行V(D)J重组，产生了一系列不同的抗原特异性受体、T细胞受体和免疫球蛋白。在许多有颌骨的脊椎动物中发现了RAG同源物。尽管它们至关重要，但在无颌脊椎动物和无脊椎动物中还没有发现同源物。本文重点介绍了人类和其他脊椎动物中基因组已完成测序的RAG同源物，并讨论了RAG同源物在系统发育和脊椎动物进化中的主要贡献。由于这两个基因的突变导致了一系列严重的联合免疫缺陷，包括Omenn综合征(OS)，因此这些话题将被详细讨论。最后，对基因组多样性的相关性和对免疫组学的影响进行了讨论。寻找同源基因可能会启发我们了解塑造适应性免疫系统的进化过程。了解适应性免疫系统的多样性对于设计和开发新的治疗方法以调节人类和/或动物模型的免疫反应至关重要。
The origin of the recombination-activating genes (RAGs) is considered to be a foundation hallmark for adaptive immunity, characterised by the presence of antigen receptor genes that provide the ability to recognise and respond to specific peptide antigens. In vertebrates, a diverse repertoire of antigen-specific receptors, T cell receptors and immunoglobulins is generated by V(D)J recombination performed by the RAG-1 and RAG-2 protein complex. RAG homologues were identified in many jawed vertebrates. Despite their crucial importance, no homologues have been found in jawless vertebrates and invertebrates. This paper focuses on the RAG homologues in humans and other vertebrates for which the genome is completely sequenced, and also discuses the main contribution of the use of RAG homologues in phylogenetics and vertebrate evolution. Since mutations in both genes cause a spectrum of severe combined immunodeficiencies, including the Omenn syndrome (OS), these topics are discussed in detail. Finally, the relevance to genomic diversity and implications to immunomics are addressed. The search for homologues could enlighten us about the evolutionary processes that shaped the adaptive immune system. Understanding the diversity of the adaptive immune system is crucially important for the design and development of new therapies to modulate the immune responses in humans and/or animal models.