title: Proteasome, transporter associated with antigen processing, and class I genes in the nurse shark Ginglymostoma cirratum: evidence for a stable class I region and MHC haplotype lineages.
abstract: Cartilaginous fish (e.g., sharks) are derived from the oldest vertebrate ancestor having an adaptive immune system, and thus are key models for examining MHC evolution. Previously, family studies in two shark species showed that classical class I (UAA) and class II genes are genetically linked. In this study, we show that proteasome genes LMP2 and LMP7, shark-specific LMP7-like, and the TAP1/2 genes are linked to class I/II. Functional LMP7 and LMP7-like genes, as well as multiple LMP2 genes or gene fragments, are found only in some sharks, suggesting that different sets of peptides might be generated depending upon inherited MHC haplotypes. Cosmid clones bearing the MHC-linked classical class I genes were isolated and shown to contain proteasome gene fragments. A non-MHC-linked LMP7 gene also was identified on another cosmid, but only two exons of this gene were detected, closely linked to a class I pseudogene (UAA-NC2); this region probably resulted from a recent duplication and translocation from the functional MHC. Tight linkage of proteasome and class I genes, in comparison with gene organizations of other vertebrates, suggests a primordial MHC organization. Another nonclassical class I gene (UAA-NC1) was detected that is linked neither to MHC nor to UAA-NC2; its high level of sequence similarity to UAA suggests that UAA-NC1 also was recently derived from UAA and translocated from MHC. These data further support the principle of a primordial class I region with few class I genes. Finally, multiple paternities in one family were demonstrated, with potential segregation distortions.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ohta
authors.forename: E Churchill
authors.initials: EC
authors.lastname: McKinney
authors.forename: Michael F
authors.initials: MF
authors.lastname: Criscitiello
authors.forename: Martin F
authors.initials: MF
authors.lastname: Flajnik
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D003360:Cosmids; D003546:Cysteine Endopeptidases / Q000235:genetics*; D005260:Female; D005805:Genes, MHC Class I; D008040:Genetic Linkage / Q000276:immunology; D006239:Haplotypes / Q000276:immunology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics*; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification; D012754:Sharks
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D009097:Multienzyme Complexes; D011506:Proteins; C073119:TAP1 protein, human; C071313:LMP-2 protein; C071692:TAP2 protein, human; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex