PDF(Pubmed)
Abstract：
A series of \"molecular domestication\" events are thought to have converted an invertebrate RAG-like (RAGL) transposase into the RAG1-RAG2 (RAG) recombinase, a critical enzyme for adaptive immunity in jawed vertebrates. The timing and order of these events are not well understood, in part because of a dearth of information regarding the invertebrate RAGL-A transposon family. In contrast to the abundant and divergent RAGL-B transposon family, RAGL-A most closely resembles RAG and is represented by a single orphan RAG1-like (RAG1L) gene in the genome of the hemichordate Ptychodera flava (PflRAG1L-A). Here, we provide evidence for the existence of complete RAGL-A transposons in the genomes of P. flava and several echinoderms. The predicted RAG1L-A and RAG2L-A proteins encoded by these transposons intermingle sequence features of jawed vertebrate RAG and RAGL-B transposases, leading to a prediction of DNA binding, catalytic, and transposition activities that are a hybrid of RAG and RAGL-B. Similarly, the terminal inverted repeats (TIRs) of the RAGL-A transposons combine features of both RAGL-B transposon TIRs and RAG recombination signal sequences. Unlike all previously described RAG2L proteins, RAG2L-A proteins contain an acidic hinge region, which we demonstrate is capable of efficiently inhibiting RAG-mediated transposition. Our findings provide evidence for a critical intermediate in RAG evolution and argue that certain adaptations thought to be specific to jawed vertebrates (e.g. the RAG2 acidic hinge) actually arose in invertebrates, thereby focusing attention on other adaptations as the pivotal steps in the completion of RAG domestication in jawed vertebrates.
摘要：
一系列“分子驯化”事件被认为已将无脊椎动物RAG样（RAGL）转座酶转化为RAG1-RAG2（RAG）重组酶，下颚脊椎动物适应性免疫的关键酶。这些事件的时间和顺序还没有得到很好的理解，部分原因是缺乏有关无脊椎动物RAGL-A转座子家族的信息。与丰富且分散的RAGL-B转座子家族相反，RAGL-A最类似于RAG，并且在半鱼鳞状黄牛（PflRAG1L-A）的基因组中由单个孤儿RAG1样（RAG1L）基因代表。这里,我们提供了在P.flava和几种棘皮动物基因组中存在完整RAGL-A转座子的证据。这些转座子编码的预测的RAG1L-A和RAG2L-A蛋白混合了颌骨脊椎动物RAG和RAGL-B转座酶的序列特征，导致DNA结合的预测，催化,和转座活动是RAG和RAGL-B的杂种。同样，RAGL-A转座子的末端反向重复(TIR)组合了RAGL-B转座子TIR和RAG重组信号序列的特征。与之前描述的所有RAG2L蛋白不同，RAG2L-A蛋白含有酸性铰链区,我们证明能够有效抑制RAG介导的转座。我们的发现为RAG进化中的关键中间体提供了证据，并认为某些适应被认为是颌骨脊椎动物特有的（例如，RAG2酸性铰链）实际上出现在无脊椎动物中，从而将注意力集中在其他适应上，作为完成下颚脊椎动物RAG驯化的关键步骤。
