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Antigen-receptor genes of the agnathan lamprey are assembled by a process involving copy choice

Abstract

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.

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Figure 1: Assembly of the LRR-encoding gene segments.
Figure 2: Asymmetrical detection of recombinants in the LRR assembly.
Figure 3: Variable junctions in the LRR module.
Figure 4: Partially assembled VLR structures.
Figure 5: A representative recombinant VLR gene isolated from a single lamprey lymphocyte-like cell.

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Acknowledgements

We thank T. Fujii (Hiroshima Prefectural University), S. Tochinai (Hokkaido University) and R. Kusakabe (RIKEN) for information about L. japonicum, and H. Sakano, T. Imai, T. Nishihara and A. Tsuboi for comments. Supported by the Ministry of Education Culture and Science of Japan.

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Correspondence to Fumikiyo Nagawa.

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Supplementary information

Supplementary Fig. 1

Structures of germline genes. (PDF 237 kb)

Supplementary Fig. 2

Identification of CP gene segments. (PDF 160 kb)

Supplementary Fig. 3

Compatibility of swapped primer pairs. (PDF 232 kb)

Supplementary Fig. 4

A model for extending the VLR gene sequence. (PDF 167 kb)

Supplementary Fig. 5

Variable junctions in the LRR segments. (PDF 178 kb)

Supplementary Fig. 6

Other examples of variable junctions within the LRR module. (PDF 224 kb)

Supplementary Table 1 (PDF 71 kb)

Supplementary Methods (PDF 101 kb)

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Nagawa, F., Kishishita, N., Shimizu, K. et al. Antigen-receptor genes of the agnathan lamprey are assembled by a process involving copy choice. Nat Immunol 8, 206–213 (2007). https://doi.org/10.1038/ni1419

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