Antigen-receptor genes of the agnathan lamprey are assembled by a process involving copy choice.
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.
Nagawa
Fumikiyo
F
Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan. snagawa@mail.ecc.u-tokyo.ac.jp
Kishishita
Natsuko
N
Shimizu
Kazumichi
K
Hirose
Satoshi
S
Miyoshi
Masato
M
Nezu
Junnya
J
Nishimura
Toshinobu
T
Nishizumi
Hirofumi
H
Takahashi
Yoshimasa
Y
Hashimoto
Shu-ichi
S
Takeuchi
Masaki
M
Miyajima
Atsushi
A
Takemori
Toshitada
T
Otsuka
Anthony J
AJ
Sakano
Hitoshi
H
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D005784:Gene Amplification / Q000235:genetics; D017353:Gene Deletion; D018628:Gene Dosage / Q000235:genetics*; D015321:Gene Rearrangement / Q000235:genetics*; D007798:Lampreys / Q000235:genetics* / Q000276:immunology; D000090263:Leucine-Rich Repeat Proteins; D008214:Lymphocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics; D011946:Receptors, Antigen / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics*; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
D000090263:Leucine-Rich Repeat Proteins; D011506:Proteins; D011946:Receptors, Antigen