title: Unraveling the evolution of the Atlantic cod's (Gadus morhua L.) alternative immune strategy.
abstract: Genes encoding the major histocompatibility complex (MHC) have been thought to play a vital role in the adaptive immune system in all vertebrates. The discovery that Atlantic cod (Gadus morhua) has lost important components of the MHC II pathway, accompanied by an unusually high number of MHC I genes, shed new light on the evolution and plasticity of the immune system of teleosts as well as in higher vertebrates. The overall aim of this study was to further investigate the highly expanded repertoire of MHC I genes using a cDNA approach to obtain sequence information of both the binding domains and the sorting signaling potential in the cytoplasmic tail. Here we report a novel combination of two endosomal sorting motifs, one tyrosine-based associated with exogenous peptide presentation by cross-presenting MHCI molecules, and one dileucine-based associated with normal MHC II functionality. The two signal motifs were identified in the cytoplasmic tail in a subset of the genes. This indicates that these genes have evolved MHC II-like functionality, allowing a more versatile use of MHC I through cross-presentation. Such an alternative immune strategy may have arisen through adaptive radiation and acquisition of new gene function as a response to changes in the habitat of its ancestral lineage.
authors.affiliation: CEES (Centre for Ecological and Evolutionary Synthesis), Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Martin
authors.initials: M
authors.lastname: Malmstrøm
authors.forename: Sissel
authors.initials: S
authors.lastname: Jentoft
authors.forename: Tone F
authors.initials: TF
authors.lastname: Gregers
authors.forename: Kjetill S
authors.initials: KS
authors.lastname: Jakobsen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D017931:DNA Primers; D048388:Gadiformes / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II
references.citation: Cytogenet Cell Genet. 1998;80(1-4):123-7
references.pmid: 9678345
references.citation: Immunol Rev. 2002 Dec;190:95-122
references.pmid: 12493009
references.citation: Science. 2010 Dec 24;330(6012):1768-73
references.pmid: 21205662
references.citation: Mol Biol Evol. 1986 Sep;3(5):418-26
references.pmid: 3444411
references.citation: Immunogenetics. 1997;46(2):129-34
references.pmid: 9162099
references.citation: Immunogenetics. 2002 Feb;53(10-11):941-63
references.pmid: 11862395
references.citation: Trends Immunol. 2005 Mar;26(3):141-9
references.pmid: 15745856
references.citation: Immunogenetics. 1999 Oct;50(1-2):49-59
references.pmid: 10541806
references.citation: Bioinformatics. 2007 Nov 1;23(21):2947-8
references.pmid: 17846036
references.citation: Curr Opin Immunol. 2010 Feb;22(1):109-17
references.pmid: 20171863
references.citation: Curr Opin Immunol. 2009 Feb;21(1):98-104
references.pmid: 19217269
references.citation: Nat Rev Immunol. 2012 Jul 13;12(8):557-69
references.pmid: 22790179
references.citation: Mol Immunol. 2007 Jul;44(15):3758-76
references.pmid: 17512596
references.citation: Immunogenetics. 2005 Jan;56(10):683-95
references.pmid: 15605248
references.citation: Immunogenetics. 2002 Feb;53(10-11):930-40
references.pmid: 11862394
references.citation: Gene. 2008 Dec 31;427(1-2):117-23
references.pmid: 18848974
references.citation: Semin Immunol. 1994 Dec;6(6):411-24
references.pmid: 7654997
references.citation: Genetics. 1998 Jul;149(3):1527-37
references.pmid: 9649539
references.citation: Nat Rev Immunol. 2005 Jun;5(6):459-71
references.pmid: 15928678
references.citation: Annu Rev Immunol. 1995;13:587-622
references.pmid: 7612235
references.citation: Nat Rev Immunol. 2011 Nov 11;11(12):823-36
references.pmid: 22076556
references.citation: Trends Microbiol. 1993 Apr;1(1):35-8
references.pmid: 8143114
references.citation: Nature. 2011 Aug 10;477(7363):207-10
references.pmid: 21832995
references.citation: Bioinformatics. 2005 May 1;21(9):2104-5
references.pmid: 15647292
references.citation: Immunogenetics. 2004 Feb;55(11):732-9
references.pmid: 14722687
references.citation: Immunol Rev. 1998 Dec;166:279-93
references.pmid: 9914919
references.citation: Nat Rev Genet. 2010 Jan;11(1):47-59
references.pmid: 19997068
references.citation: Fish Shellfish Immunol. 2009 Aug;27(2):112-9
references.pmid: 19084603
references.citation: Mol Biol Evol. 2011 Oct;28(10):2731-9
references.pmid: 21546353
references.citation: Annu Rev Cell Dev Biol. 1996;12:575-625
references.pmid: 8970738
references.citation: Genome Res. 2004 Jun;14(6):1188-90
references.pmid: 15173120
references.citation: Immunogenetics. 2006 Apr;58(2-3):152-67
references.pmid: 16518622
references.citation: Annu Rev Biochem. 2003;72:395-447
references.pmid: 12651740
references.citation: Immunol Rev. 1999 Dec;172:171-87
references.pmid: 10631946
references.citation: PLoS One. 2008 Sep 19;3(9):e3247
references.pmid: 18802471
references.citation: Nature. 1988 Sep 8;335(6186):167-70
references.pmid: 3412472
references.citation: Immunogenetics. 2000 Feb;51(2):108-16
references.pmid: 10663573
references.citation: Bioinformatics. 2003 Aug 12;19(12):1572-4
references.pmid: 12912839
references.citation: Trends Ecol Evol. 1998 Aug 1;13(8):305-11
references.pmid: 21238318
references.citation: Immunogenetics. 1997;46(1):63-72
references.pmid: 9148790
references.citation: Science. 2001 Dec 14;294(5550):2310-4
references.pmid: 11743192
references.citation: Nature. 1987 Oct 8-14;329(6139):506-12
references.pmid: 3309677
references.citation: Annu Rev Immunol. 1998;16:323-58
references.pmid: 9597133
references.citation: Immunol Rev. 1999 Feb;167:81-100
references.pmid: 10319253
references.citation: J Immunol. 1999 Jul 15;163(2):774-86
references.pmid: 10395670
references.citation: Curr Opin Cell Biol. 1989 Aug;1(4):617-23
references.pmid: 2576381
references.citation: Dev Comp Immunol. 1999 Mar-Apr;23(2):107-11
references.pmid: 10227478
references.citation: Fish Shellfish Immunol. 2011 Jan;30(1):330-9
references.pmid: 21078394
references.citation: Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10326-31
references.pmid: 10468607
references.citation: Bioinformatics. 2005 Feb 15;21(4):456-63
references.pmid: 15608047
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4712-7
references.pmid: 10781076
references.citation: Scand J Immunol. 2009 Sep;70(3):184-93
references.pmid: 19703008
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15801-6
references.pmid: 19717423
references.citation: BMC Genomics. 2010 Mar 05;11:154
references.pmid: 20205726
references.citation: Science. 1995 Jan 13;267(5195):243-6
references.pmid: 7809629
references.citation: Bioessays. 2012 Aug;34(8):648-51
references.pmid: 22499250
references.citation: Immunol Today. 1996 Mar;17(3):131-7
references.pmid: 8820271
references.citation: Nat Rev Immunol. 2010 Aug;10(8):543-53
references.pmid: 20651744
references.citation: APMIS. 1992 May;100(5):383-92
references.pmid: 1586476