New insights into the evolutionary origins of the recombination-activating gene proteins and V(D)J recombination.
New insights into the evolutionary origins of the recombination-activating gene proteins and V(D)J recombination.
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DOI：
10.1111/febs.13990
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Schatz DG
中科院分区：
文献类型：
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作者：
Carmona LM;Schatz DG
颌骨脊椎动物的获得性免疫系统依赖于V(D)J重组作为主要过程之一，以产生识别广泛病原体所需的各种受体阵列。从一系列潜在基因片段中组装抗原受体基因所需的DNA切割反应是由重组激活基因蛋白RAG1和RAG2介导的。RAG蛋白被认为起源于转座元件(TE)，因为它们与几个转座酶家族在机制和结构上有相似之处，并且本身能够介导转座。已经鉴定了一些与RAG1和RAG2序列相似的RAG样蛋白和TES，但直到最近才开始表征它们的功能，揭示了它们与脊椎动物RAG的机制联系。特别重要的是ProtoRAG的发现，这是在文昌鱼基本脊索动物基因组中发现的一个转座子超家族。ProtoRAG具有许多预测的祖先RAG转座子的序列和机制特征，很可能是RAG1和RAG2的进化亲戚。此外，早期的观察表明，在RAG2缺失的情况下，RAG1能够介导V(D)J重组，这意味着这两个RAG基因的进化起源是独立的。本文综述了近年来在鉴定和鉴定RAG样蛋白及其编码的TES方面的最新进展，并提出了V(D)J重组和RAG蛋白进化的改进模型。V(D)J重组是在有颌骨脊椎动物中组装和产生淋巴细胞抗原受体基因多样性的过程，并支持适应性免疫系统。这一过程是由重组激活基因(RAG)蛋白介导的。本文就RAG蛋白的出现和分化以及V(D)J重组的进化等方面的已知特征和最新进展作一综述。
The adaptive immune system of jawed vertebrates relies on V(D)J recombination as one of the main processes to generate the diverse array of receptors necessary for the recognition of a wide range of pathogens. The DNA cleavage reaction necessary for the assembly of the antigen receptor genes from an array of potential gene segments is mediated by the Recombination Activating Gene proteins RAG1 and RAG2. The RAG proteins have been proposed to originate from a transposable element (TE) as they share mechanistic and structural similarities with several families of transposases and are themselves capable of mediating transposition. A number of RAG-like proteins and TEs with sequence similarity to RAG1 and RAG2 have been identified, but only recently has their function begun to be characterized, revealing mechanistic links to the vertebrate RAGs. Of particular significance is the discovery of ProtoRAG, a transposon superfamily found in the genome of the basal chordate amphioxus. ProtoRAG has many of the sequence and mechanistic features predicted for the ancestral RAG transposon and is likely to be an evolutionary relative of RAG1 and RAG2. In addition, early observations suggesting that RAG1 is able to mediate V(D)J recombination in the absence of RAG2 have been confirmed, implying independent evolutionary origins for the two RAG genes. Here, recent progress in identifying and characterizing RAG-like proteins and the TEs that encode them is summarized and a refined model for the evolution of V(D)J recombination and the RAG proteins is presented. V(D)J recombination is the process that assembles and generates diversity in lymphocyte antigen receptor genes and underpins the adaptive immune system in jawed vertebrates. This process is mediated by the Recombination Activating Gene (RAG) proteins. In this review, we highlight the known features and the latest progress on the emergence and divergence of the RAG proteins and the evolution of V(D)J recombination.