title: Elephant shark genome provides unique insights into gnathostome evolution.
abstract: The emergence of jawed vertebrates (gnathostomes) from jawless vertebrates was accompanied by major morphological and physiological innovations, such as hinged jaws, paired fins and immunoglobulin-based adaptive immunity. Gnathostomes subsequently diverged into two groups, the cartilaginous fishes and the bony vertebrates. Here we report the whole-genome analysis of a cartilaginous fish, the elephant shark (Callorhinchus milii). We find that the C. milii genome is the slowest evolving of all known vertebrates, including the 'living fossil' coelacanth, and features extensive synteny conservation with tetrapod genomes, making it a good model for comparative analyses of gnathostome genomes. Our functional studies suggest that the lack of genes encoding secreted calcium-binding phosphoproteins in cartilaginous fishes explains the absence of bone in their endoskeleton. Furthermore, the adaptive immune system of cartilaginous fishes is unusual: it lacks the canonical CD4 co-receptor and most transcription factors, cytokines and cytokine receptors related to the CD4 lineage, despite the presence of polymorphic major histocompatibility complex class II molecules. It thus presents a new model for understanding the origin of adaptive immunity.
authors.affiliation: 1] Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673 [2] Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
authors.forename: Byrappa
authors.initials: B
authors.lastname: Venkatesh
authors.affiliation: Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
authors.forename: Alison P
authors.initials: AP
authors.lastname: Lee
authors.affiliation: Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
authors.forename: Vydianathan
authors.initials: V
authors.lastname: Ravi
authors.affiliation: Developmental and Biomedical Genetics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Maurya
authors.affiliation: Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Lian
authors.affiliation: Department of Developmental Immunology, Max-Planck-Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
authors.forename: Jeremy B
authors.initials: JB
authors.lastname: Swann
authors.affiliation: Department of Microbiology and Immunology, University of Maryland, Baltimore, Maryland 21201, USA.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ohta
authors.affiliation: Department of Microbiology and Immunology, University of Maryland, Baltimore, Maryland 21201, USA.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Flajnik
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sutoh
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kasahara
authors.affiliation: Molecular Engineering Laboratory, Biomedical Sciences Institutes, A*STAR, Biopolis, Singapore 138673.
authors.forename: Shawn
authors.initials: S
authors.lastname: Hoon
authors.affiliation: Molecular Engineering Laboratory, Biomedical Sciences Institutes, A*STAR, Biopolis, Singapore 138673.
authors.forename: Vamshidhar
authors.initials: V
authors.lastname: Gangu
authors.affiliation: Department of Biology, San Francisco State University, San Francisco, California 94132, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Roy
authors.affiliation: Banting and Best Department of Medical Research and Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Manuel
authors.initials: M
authors.lastname: Irimia
authors.affiliation: Fish Developmental Biology Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Korzh
authors.affiliation: Fish Developmental Biology Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
authors.forename: Igor
authors.initials: I
authors.lastname: Kondrychyn
authors.affiliation: Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
authors.forename: Zhi Wei
authors.initials: ZW
authors.lastname: Lim
authors.affiliation: Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
authors.forename: Boon-Hui
authors.initials: BH
authors.lastname: Tay
authors.affiliation: Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
authors.forename: Sumanty
authors.initials: S
authors.lastname: Tohari
authors.affiliation: Molecular Engineering Laboratory, Biomedical Sciences Institutes, A*STAR, Biopolis, Singapore 138673.
authors.forename: Kiat Whye
authors.initials: KW
authors.lastname: Kong
authors.affiliation: Molecular Engineering Laboratory, Biomedical Sciences Institutes, A*STAR, Biopolis, Singapore 138673.
authors.forename: Shufen
authors.initials: S
authors.lastname: Ho
authors.affiliation: 1] Institut de Biologia Evolutiva (UPF-CSIC), PRBB, 08003 Barcelona, Spain [2] Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Catalonia, Spain.
authors.forename: Belen
authors.initials: B
authors.lastname: Lorente-Galdos
authors.affiliation: 1] Institut de Biologia Evolutiva (UPF-CSIC), PRBB, 08003 Barcelona, Spain [2] Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Catalonia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Quilez
authors.affiliation: 1] Institut de Biologia Evolutiva (UPF-CSIC), PRBB, 08003 Barcelona, Spain [2] Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Catalonia, Spain.
authors.forename: Tomas
authors.initials: T
authors.lastname: Marques-Bonet
authors.affiliation: Center for Biomolecular Science and Engineering, School of Engineering, University of California Santa Cruz, Santa Cruz, California 95064, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Raney
authors.affiliation: Developmental and Biomedical Genetics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Ingham
authors.affiliation: Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
authors.forename: Alice
authors.initials: A
authors.lastname: Tay
authors.affiliation: The Genome Institute at Washington University, St Louis, Missouri 63108, USA.
authors.forename: LaDeana W
authors.initials: LW
authors.lastname: Hillier
authors.affiliation: The Genome Institute at Washington University, St Louis, Missouri 63108, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Minx
authors.affiliation: Department of Developmental Immunology, Max-Planck-Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Boehm
authors.affiliation: The Genome Institute at Washington University, St Louis, Missouri 63108, USA.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.affiliation: Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
authors.forename: Sydney
authors.initials: S
authors.lastname: Brenner
authors.affiliation: The Genome Institute at Washington University, St Louis, Missouri 63108, USA.
authors.forename: Wesley C
authors.initials: WC
authors.lastname: Warren
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D019070:Cell Lineage / Q000276:immunology; D019143:Evolution, Molecular; D029941:Fish Proteins / Q000145:classification / Q000235:genetics; D017353:Gene Deletion; D016678:Genome / Q000235:genetics*; D023281:Genomics; D007111:Immunity, Cellular / Q000235:genetics; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D010012:Osteogenesis / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D017434:Protein Structure, Tertiary / Q000235:genetics; D012754:Sharks / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014714:Vertebrates / Q000145:classification / Q000235:genetics; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development
chemical_list: D029941:Fish Proteins; D010750:Phosphoproteins; D002118:Calcium