title: The evolution of multiple isotypic IgM heavy chain genes in the shark.
abstract: The IgM H chain gene organization of cartilaginous fishes consists of 15-200 miniloci, each with a few gene segments (V(H)-D1-D2-J(H)) and one C gene. This is a gene arrangement ancestral to the complex IgH locus that exists in all other vertebrate classes. To understand the molecular evolution of this system, we studied the nurse shark, which has relatively fewer loci, and characterized the IgH isotypes for organization, functionality, and the somatic diversification mechanisms that act upon them. Gene numbers differ slightly between individuals ( approximately 15), but five active IgM subclasses are always present. Each gene undergoes rearrangement that is strictly confined within the minilocus; in B cells there is no interaction between adjacent loci located > or =120 kb apart. Without combinatorial events, the shark IgM H chain repertoire is based on junctional diversity and, subsequently, somatic hypermutation. We suggest that the significant contribution by junctional diversification reflects the selected novelty introduced by RAG in the early vertebrate ancestor, whereas combinatorial diversity coevolved with the complex translocon organization. Moreover, unlike other cartilaginous fishes, there are no germline-joined VDJ at any nurse shark mu locus, and we suggest that such genes, when functional, are species-specific and may have specialized roles. With an entire complement of IgM genes available for the first time, phylogenetic analyses were performed to examine how the multiple Ig loci evolved. We found that all domains changed at comparable rates, but V(H) appears to be under strong positive selection for increased amino acid sequence diversity, and surprisingly, so does Cmicro2.
authors.affiliation: Department of Physiology and Pharmacology, State University of New York Health Science Center, Brooklyn, NY 11203, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Lee
authors.forename: Jing Li
authors.initials: JL
authors.lastname: Huang
authors.forename: Ming Fai
authors.initials: MF
authors.lastname: Lui
authors.forename: Karolina
authors.initials: K
authors.lastname: Malecek
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ohta
authors.forename: Arne
authors.initials: A
authors.lastname: Mooers
authors.forename: Ellen
authors.initials: E
authors.lastname: Hsu
mesh_terms: D000818:Animals; D001483:Base Sequence; D019143:Evolution, Molecular; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005796:Genes; D050438:Genes, Immunoglobulin Heavy Chain; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment; D012754:Sharks / Q000235:genetics* / Q000276:immunology
chemical_list: D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M