title: 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.
authors.affiliation: 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
authors.forename: Fumikiyo
authors.initials: F
authors.lastname: Nagawa
authors.forename: Natsuko
authors.initials: N
authors.lastname: Kishishita
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Shimizu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirose
authors.forename: Masato
authors.initials: M
authors.lastname: Miyoshi
authors.forename: Junnya
authors.initials: J
authors.lastname: Nezu
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Nishimura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nishizumi
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
authors.forename: Toshitada
authors.initials: T
authors.lastname: Takemori
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Otsuka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakano
mesh_terms: 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
chemical_list: D000090263:Leucine-Rich Repeat Proteins; D011506:Proteins; D011946:Receptors, Antigen