title: Organization of lamprey variable lymphocyte receptor C locus and repertoire development.
abstract: Jawless vertebrates are pivotal representatives for studies of the evolution of adaptive immunity due to their unique position in chordate phylogeny. Lamprey and hagfish, the extant jawless vertebrates, have an alternative lymphocyte-based adaptive immune system that is based on somatically diversifying leucine-rich repeat (LRR)-based antigen receptors, termed variable lymphocyte receptors (VLRs). Lamprey T-like and B-like lymphocyte lineages have been shown to express VLRA and VLRB types of anticipatory receptors, respectively. An additional VLR type, termed VLRC, has recently been identified in arctic lamprey (Lethenteron camtschaticum), and our analysis indicates that VLRC sequences are well conserved in sea lamprey (Petromyzon marinus), L. camtschaticum, and European brook lamprey (Lampetra planeri). Genome sequences of P. marinus were analyzed to determine the organization of the VLRC-encoding locus. In addition to the incomplete germ-line VLRC gene, we have identified 182 flanking donor genomic sequences that could be used to complete the assembly of mature VLRC genes. Donor LRR cassettes were classifiable into five basic structural groups, the composition of which determines their order of use during VLRC assembly by virtue of sequence similarities to the incomplete germ-line gene and to one another. Bidirectional VLRC assembly was predicted by comparisons of mature VLRC genes with the sequences of donor LRR cassettes and verified by analysis of partially assembled intermediates. Biased and repetitive use of certain donor LRR cassettes was demonstrable in mature VLRCs. Our analysis provides insight into the unique molecular strategies used for VLRC gene assembly and repertoire diversification.
authors.affiliation: Emory Vaccine Center, and Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Sabyasachi
authors.initials: S
authors.lastname: Das
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hirano
authors.forename: Narges
authors.initials: N
authors.lastname: Aghaallaei
authors.forename: Baubak
authors.initials: B
authors.lastname: Bajoghli
authors.forename: Thomas
authors.initials: T
authors.lastname: Boehm
authors.forename: Max D
authors.initials: MD
authors.lastname: Cooper
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D015321:Gene Rearrangement; D016678:Genome; D023281:Genomics; D008969:Molecular Sequence Data; D048428:Petromyzon / Q000235:genetics*; D010802:Phylogeny; D011946:Receptors, Antigen / Q000235:genetics*; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
chemical_list: D011946:Receptors, Antigen