Antigen-receptor genes of the agnathan lamprey are assembled by a process involving copy choice
Antigen-receptor genes of the agnathan lamprey are assembled by a process involving copy choice
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DOI：
10.1038/ni1419
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发表时间：
2007-02-01
影响因子：
30.5
通讯作者：
Sakano, Hitoshi
中科院分区：
文献类型：
--
作者：
Nagawa, Fumikiyo;Kishishita, Natsuko;Sakano, Hitoshi
无颌脊椎动物具有获得性免疫，但没有免疫球蛋白型抗原受体。可变淋巴细胞受体（VLRs）已被确定在七鳃鳗，由多个富含亮氨酸的重复（LRR）模块。活性VLR基因是由一系列可变基因片段组装而成，其中包括许多编码LRR的基因片段。基因片段的逐步组装似乎是通过替换5'和3'恒定区基因之间的插入DNA而发生的。在这里，我们报告七鳃鳗（日本白鲑）组装其VLR基因的过程中，涉及“拷贝选择”。短同源性区域似乎是将供体LRR编码序列复制到受体基因中的启动子。这些LRR编码种系序列是丰富的，并共享广泛的序列同源性。这样的基因组组织允许在LRR编码模块中的任何地方开始复制以产生各种杂交LRR。因此，不仅可以通过以不同组合复制各种LRR区段，而且可以通过使用LRR基因区段中的多个位点进行引发来产生大量重组VLR基因库。
Jawless vertebrates have acquired immunity but do not have immunoglobulin-type antigen receptors. Variable lymphocyte receptors (VLRs) have been identified in lamprey that consist of multiple leucine-rich repeat (LRR) modules. An active VLR gene is generated by the assembly of a series of variable gene segments, including many that encode LRRs. Stepwise assembly of the gene segments seems to occur by replacement of the intervening DNA between the 5' and 3' constant-region genes. Here we report that lamprey (Lethenteron japonicum) assemble their VLR genes by a process involving 'copy choice'. Regions of short homology seemed to prime copying of donor LRR-encoding sequences into the recipient gene. Those LRR-encoding germline sequences were abundant and shared extensive sequence homologies. Such genomic organization permits initiation of copying anywhere in an LRR-encoding module for the generation of various hybrid LRRs. Thus, a vast repertoire of recombinant VLR genes could be generated not only by copying of various LRR segments in diverse combinations but also by the use of multiple sites in an LRR gene segment for priming.