title: Salmonid genomes have a remarkably expanded akirin family, coexpressed with genes from conserved pathways governing skeletal muscle growth and catabolism.
abstract: Metazoan akirin genes regulate innate immunity, myogenesis, and carcinogenesis. Invertebrates typically have one family member, while most tetrapod and teleost vertebrates have one to three. We demonstrate an expanded repertoire of eight family members in genomes of four salmonid fishes, owing to paralog preservation after three tetraploidization events. Retention of paralogs secondarily lost in other teleosts may be related to functional diversification and posttranslational regulation. We hypothesized that salmonid akirins would be transcriptionally regulated in fast-twitch skeletal muscle during activation of conserved pathways governing catabolism and growth. The in vivo nutritional state of Arctic charr (Salvelinus alpinus L.) was experimentally manipulated, and transcript levels for akirin family members and 26 other genes were measured by quantitative real-time PCR (qPCR), allowing the establishment of a similarity network of expression profiles. In fasted muscle, a class of akirins was upregulated, with one family member showing high coexpression with catabolic genes coding the NF-kappaB p65 subunit, E2 ubiquitin-conjugating enzymes, E3 ubiquitin ligases, and IGF-I receptors. Another class of akirin was upregulated with subsequent feeding, coexpressed with 14-3-3 protein genes. There was no similarity between expression profiles of akirins with IGF hormones or binding protein genes. The level of phylogenetic relatedness of akirin family members was not a strong predictor of transcriptional responses to nutritional state, or differences in transcript abundance levels, indicating a complex pattern of regulatory evolution. The salmonid akirins epitomize the complexity linking the genome to physiological phenotypes of vertebrates with a history of tetraploidization.
authors.affiliation: Scottish Ocean Institute, School of Biology, University of St Andrews, St Andrews, United Kingdom. djm59@st-andrews.ac.uk
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Macqueen
authors.forename: Bjarni K
authors.initials: BK
authors.lastname: Kristjánsson
authors.forename: Ian A
authors.initials: IA
authors.lastname: Johnston
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016000:Cluster Analysis; D029941:Fish Proteins / Q000145:classification / Q000235:genetics*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D016678:Genome / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism*; D010802:Phylogeny; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012474:Salmon / Q000235:genetics* / Q000254:growth & development; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000235:genetics; D014337:Trout / Q000235:genetics* / Q000254:growth & development
chemical_list: D029941:Fish Proteins
references.citation: Exp Cell Res. 2008 Mar 10;314(5):1013-29
references.pmid: 18255059
references.citation: Oncogene. 2001 Oct 1;20(44):6331-8
references.pmid: 11607836
references.citation: BMC Evol Biol. 2009 Feb 06;9:34
references.pmid: 19200367
references.citation: Trends Biochem Sci. 1999 Jan;24(1):34-6
references.pmid: 10087920
references.citation: J Mol Biol. 1999 Dec 17;294(5):1351-62
references.pmid: 10600390
references.citation: BMC Evol Biol. 2007 Nov 08;7:214
references.pmid: 17996036
references.citation: Proc Natl Acad Sci U S A. 1978 Nov;75(11):5575-9
references.pmid: 281706
references.citation: J Cell Biol. 2009 Jun 15;185(6):1083-95
references.pmid: 19506036
references.citation: J Cell Biol. 2008 Feb 25;180(4):787-802
references.pmid: 18299349
references.citation: Nucleic Acids Res. 2009 Apr;37(6):e45
references.pmid: 19237396
references.citation: Curr Biol. 2001 Feb 6;11(3):171-6
references.pmid: 11231151
references.citation: Mol Biol Evol. 2000 Apr;17(4):540-52
references.pmid: 10742046
references.citation: Cancer Res. 2004 Aug 1;64(15):5245-50
references.pmid: 15289330
references.citation: Clin Chem. 2009 Apr;55(4):611-22
references.pmid: 19246619
references.citation: Am J Physiol Regul Integr Comp Physiol. 2003 May;284(5):R1277-86
references.pmid: 12676749
references.citation: Cell. 2004 Oct 15;119(2):285-98
references.pmid: 15479644
references.citation: Bioinformatics. 2005 Apr 1;21(7):1280-1
references.pmid: 15546938
references.citation: BMC Genomics. 2008 Aug 02;9:372
references.pmid: 18673577
references.citation: Nucleic Acids Res. 2001 Sep 1;29(17):3513-9
references.pmid: 11522820
references.citation: Comp Biochem Physiol B Biochem Mol Biol. 2002 Dec;133(4):609-46
references.pmid: 12470823
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2274-9
references.pmid: 16461893
references.citation: J Endocrinol. 2007 Jan;192(1):149-58
references.pmid: 17210752
references.citation: Nature. 2008 Jun 19;453(7198):1064-71
references.pmid: 18563158
references.citation: Bioinformatics. 2005 May 1;21(9):2104-5
references.pmid: 15647292
references.citation: Am J Physiol Cell Physiol. 2004 Oct;287(4):C834-43
references.pmid: 15355854
references.citation: Front Zool. 2009 Aug 24;6:18
references.pmid: 19703292
references.citation: Curr Biol. 1994 Nov 1;4(11):973-82
references.pmid: 7874496
references.citation: J Biol Chem. 2008 Jul 4;283(27):18753-64
references.pmid: 18460465
references.citation: Int J Biochem Cell Biol. 2005 Oct;37(10):1974-84
references.pmid: 16087388
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9033-8
references.pmid: 15175431
references.citation: Syst Biol. 2003 Oct;52(5):696-704
references.pmid: 14530136
references.citation: Nature. 2004 Oct 21;431(7011):946-57
references.pmid: 15496914
references.citation: J Cell Sci. 2006 Sep 1;119(Pt 17):3695-704
references.pmid: 16931600
references.citation: Bioinformatics. 2003 Aug 12;19(12):1572-4
references.pmid: 12912839
references.citation: Vaccine. 2006 May 8;24(19):4082-95
references.pmid: 16580098
references.citation: Genetics. 2003 Aug;164(4):1261-9
references.pmid: 12930737
references.citation: Mol Biol Evol. 2007 Aug;24(8):1596-9
references.pmid: 17488738
references.citation: Exp Cell Res. 2009 Jul 15;315(12):2012-21
references.pmid: 19406121
references.citation: Gen Comp Endocrinol. 2007 Feb;150(3):462-72
references.pmid: 17196198
references.citation: Science. 2003 Dec 5;302(5651):1727-36
references.pmid: 14605208
references.citation: Gen Comp Endocrinol. 2003 Jun 15;132(2):209-15
references.pmid: 12812767
references.citation: FASEB J. 2003 Jun;17(9):1048-57
references.pmid: 12773487
references.citation: Nat Immunol. 2008 Jan;9(1):97-104
references.pmid: 18066067
references.citation: J Exp Biol. 2008 Dec;211(Pt 24):3859-70
references.pmid: 19043058
references.citation: Nat Rev Immunol. 2002 Oct;2(10):725-34
references.pmid: 12360211
references.citation: PLoS One. 2008 Feb 06;3(2):e1567
references.pmid: 18253507
references.citation: Brief Bioinform. 2008 Jul;9(4):286-98
references.pmid: 18372315
references.citation: Mol Biol Evol. 2006 Oct;23(10):1937-45
references.pmid: 16864604