Polymorphism, selection and tandem duplication of transferrin genes in Atlantic cod (Gadus morhua) - Conserved synteny between fish monolobal and tetrapod bilobal transferrin loci

BMC Genetics

Carl André²  Petra E Petersen¹  Ave Tooming-Klunderud⁵  Davide Pirolli⁴  Maria Cristina De Rosa⁴  Øivind Andersen³ 

[1] Aquaculture Research Station of the Faroes, FO-430 Hvalvík, Faroe Islands;Department of Marine Ecology-Tjärnö, Gothenburg University, S-45296 Strömstad, Sweden;Norwegian University of Life Sciences, P. O. Box 5003, N-1430 Ås, Norway;Institute of Chemistry of Molecular Recognition - CNR and Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, 00168 Rome, Italy;Centre for Ecological and Evolutionary Synthesis (CEES), Department of Biology, University of Oslo, P.O. Box 1066 Blindern, N-0316 Oslo, Norway

关键词: molecular modeling;    positive selection;    adaptation;    tandem duplication;    Atlantic cod;    Monolobal transferrin;   

Others  :  1127006
DOI  :  10.1186/1471-2156-12-51

 received in 2011-01-21, accepted in 2011-05-25,  发布年份 2011

【 摘 要 】

Background

The two homologous iron-binding lobes of transferrins are thought to have evolved by gene duplication of an ancestral monolobal form, but any conserved synteny between bilobal and monolobal transferrin loci remains unexplored. The important role played by transferrin in the resistance to invading pathogens makes this polymorphic gene a highly valuable candidate for studying adaptive divergence among local populations.

Results

The Atlantic cod genome was shown to harbour two tandem duplicated serum transferrin genes (Tf1, Tf2), a melanotransferrin gene (MTf), and a monolobal transferrin gene (Omp). Whereas Tf1 and Tf2 were differentially expressed in liver and brain, the Omp transcript was restricted to the otoliths. Fish, chicken and mammals showed highly conserved syntenic regions in which monolobal and bilobal transferrins reside, but contrasting with tetrapods, the fish transferrin genes are positioned on three different linkage groups. Sequence alignment of cod Tf1 cDNAs from Northeast (NE) and Northwest (NW) Atlantic populations revealed 22 single nucleotide polymorphisms (SNP) causing the replacement of 16 amino acids, including eight surface residues revealed by the modelled 3D-structures, that might influence the binding of pathogens for removal of iron. SNP analysis of a total of 375 individuals from 14 trans-Atlantic populations showed that the Tf1-NE variant was almost fixed in the Baltic cod and predominated in the other NE Atlantic populations, whereas the NW Atlantic populations were more heterozygous and showed high frequencies of the Tf-NW SNP alleles.

Conclusions

The highly conserved synteny between fish and tetrapod transferrin loci infers that the fusion of tandem duplicated Omp-like genes gave rise to the modern transferrins. The multiple nonsynonymous substitutions in cod Tf1 with putative structural effects, together with highly divergent allele frequencies among different cod populations, strongly suggest evidence for positive selection and local adaptation in trans-Atlantic cod populations.

【 授权许可】

   
2011 Andersen et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】

• [1]Ruzzante DE, Taggart CT, Cook D: A nuclear DNA basis for shelf and bank-scale population structure in NW Atlantic cod (Gadus morhua): Labrador to Georges Bank. Mol Ecol 1998, 7:1663-1680. 1998
• [2]Bekkevold D, André C, Dahlgren TG, Clausen LAW, Torstensen E, Mosegaard H, et al.: Environmental correlates of population differentiation in Atlantic herring. Evolution 2005, 59:2656-2668.
• [3]Hauser L, Carvalho GR: Paradigm shifts in marine fisheries genetics: ugly hypotheses slain by beautiful facts. Fish Fisheries 2008, 9:333-362.
• [4]Naish KA, Hard JJ: Bridging the gap between the genotype and the phenotype: linking genetic variation, selection and adaptation in fishes. Fish and Fisheries 2008, 9:369-422.
• [5]Nielsen EE, Hemmer-Hansen J, Larsen PF, Bekkevold D: Population genomics of marine fishes: identifying adaptive variation in space and time. Mol Ecol 2009, 18:3128-3150.
• [6]Barrett RDH, Rogers SM, Schluter D: Natural selection on a major armor gene in threespine stickleback. Science 2008, 322:255-257.
• [7]Hemmer-Hansen J, Nielsen EE, Frydenberg J, Loeschcke V: Adaptive divergence in a high gene flow environment: Hsc70 variantion in the European flounder (Platichthys flesus L.). Heredity 2007, 99:592-600.
• [8]Schulte PM, Glemet HC, Fiebig AA, Powers DA: Adaptive variation in lactate dehydrogenase-B gene expression: role of a stress-responsive regulatory element. Proc Natl Acad Sci USA 2000, 97:6597-6602.
• [9]Pampoulie C, Jakobsdóttir KB, Marteinsdóttir G, Thorsteinsson V: Are vertical behaviour patterns related to the pantophysin locus in the Atlantic cod (Gadus morhua L.)? Behav Genet 2008, 38:76-81.
• [10]Johnston IA, Andersen Ø: Number of muscle fibres in adult Atlantic cod varies with temperature during embryonic development. Aquatic Biol 2008, 4:167-173.
• [11]Andersen O, Wetten OF, De Rosa MC, Andre C, Carelli Alinovi C, Colafranceschi M, Brix O, Colosimo A: Haemoglobin polymorphisms affect the oxygen-binding properties in Atlantic cod populations. Proc Biol Sci B 2009, 276:833-41.
• [12]Moen T, Hayes B, Nilsen F, Delghandi M, Fjalestad KT, Fevolden SE, Berg PR, Lien S: Identification and characterisation of novel SNP markers in Atlantic cod: evidence for directional selection. BMC Genet 2008, 9:18.
• [13]Nielsen EE, Hemmer-Hansen J, Poulsen NA, Loeschcke V, Moen T, Johansen T, Mittelholzer C, Taranger GL, Ogden R, Carvalho G: Genomic signatures of local directional selection in a high gene flow marine organism; the Atlantic cod (Gadus morhua). BMC Evol Biol 2009, 9:276. BioMed Central Full Text
• [14]Bradbury IR, Hubert S, Higgins B, Borza T, Bowman S, Paterson IG, Snelgrove PV, Morris CJ, Gregory RS, Hardie DC, Hutchings JA, Ruzzante DE, Taggart CT, Bentzen P: Parallel adaptive evolution of Atlantic cod on both sides of the Atlantic Ocean in response to temperature. Proc Biol Sci 2010, 277:3725-3734.
• [15]Lash A, Saleem A: Iron metabolism and its regulation. Ann Clin Lab Sci 1995, 25:20-30.
• [16]Anderson GJ, Vulpe CD: Mammalian iron transport. Cell Mol Life Sci 2009, 66:3241-3261.
• [17]Greene FC, Feeney RE: Physical evidence for transferrins as single polypeptide chains. Biochemistry 1968, 7:1366-1371.
• [18]Park I, Schaeffer E, Sidoli A, Baralle FE, Cohen GN, Zakin MM: Organization of the human transferrin gene: direct evidence that it originated by gene duplication. Proc Natl Acad Sci USA 1985, 82:3149-153.
• [19]Nichol H, Law JH, Winzerling JJ: Iron metabolism in insects. Annu Rev Entomol 2002, 47:535-559.
• [20]Aisen P, Leibman A, Sia CL: Molecular weight and subunit structure of hagfish transferrin. Biochemistry 1972, 11:3461-3464.
• [21]Sylvester SR, Roy A: A 3'-truncated transferrin messenger RNA is expressed in rat testicular germ cells. Biol Reprod 2002, 67:895-899.
• [22]Martin AW, Huebers E, Huebers H, Webb J, Finch CA: A mono-sited transferrin from a representative deuterostome: the ascidian Pyura stolonifera (subphylum Urochordata). Blood 1984, 64:1047-1052.
• [23]Abe Y, Nagata R, Hasunuma Y, Yokosawa H: Isolation, characterization and cDNA cloning of a one-lobed transferrin from the ascidian Halocynthia roretzi. Comp Biochem Physiol B 2001, 128:73-79.
• [24]Tinoco AD, Peterson CW, Lucchese B, Doyle RP, Valentine AM: On the evolutionary significance and metal-binding characteristics of a monolobal transferrin from Ciona intestinalis. Proc Natl Acad Sci USA 2008, 105:3268-3273.
• [25]Murayama E, Okuno A, Ohira T, Takagi Y, Nagasawa H: Molecular cloning and expression of an otolith matrix protein cDNA from the rainbow trout, Oncorhynchus mykiss. Comp Biochem Physiol B 2000, 126:511-520.
• [26]Murayama E, Takagi Y, Nagasawa H: Immunohistochemical localization of two otolith matrix proteins in the otolith and inner ear of the rainbow trout, Oncorhynchus mykiss: comparative aspects between the adult inner ear and embryonic otocysts. Histochem Cell Biol 2004, 121:155-166.
• [27]Murayama E, Herbomel P, Kawakami A, Takeda H, Nagasawa H: Otolith matrix proteins OMP-1 and Otolin-1 are necessary for normal otolith growth and their correct anchoring onto the sensory maculae. Mech Dev 2005, 122:791-803.
• [28]Lambert LA, Perri H, Meehan TJ: Evolution of duplications in the transferrin family of proteins. Comp Biochem Physiol B 2005, 140:11-25.
• [29]Ong ST, Ho JZ, Ho B, Ding JL: Iron-withholding strategy in innate immunity. Immunobiology 2006, 211:295-314.
• [30]Ganz T: Iron in innate immunity: starve the invaders. Curr Opin Immunol 2009, 21:63-67.
• [31]Macedo MF, de Sousa M, Ned RM, Mascarenhas C, Andrews NC, Correia-Neves M: Transferrin is required for early T-cell differentiation. Immunology 2004, 112:543-9.
• [32]Neves JV, Wilson JM, Rodrigues PNS: Transferrin and ferritin response to bacterial infection: The role of the liver and brain in fish. Dev Comp Immunol 2009, 33:848-857.
• [33]Ratledge C, Dover LG: Iron metabolism in pathogenic bacteria. Annu Rev Microbiol 2000, 54:881-941.
• [34]Newton JR, Wood JLN, Chanter N: Evidence for transferrin allele as a host-level risk factor in naturally occurring equine respiratory disease: a preliminary study. Equine Vet J 2007, 39:164-171.
• [35]Jurecka P, Wiegertjes GF, Rakus KL, Pilarczyk A, Irnazarow I: Genetic resitance of carp (Cyprinus carpio L.) to Trypanosoma borreli: Influence of transferrin polymorphisms. Vet Immunol Immunopath 2009, 127:19-25.
• [36]Bigg GR, Cunningham CW, Ottersen G, Pogson GH, Wadley MR, Williamson P: Ice-age survival of Atlantic cod: agreement between palaeoecology models and genetics. Proc R Soc B-Biol Sci 2008, 275:163-173.
• [37]Carr SM, Marshall HD: Intraspecific phylogeographic genomics from multiple complete mtDNA genomes in Atlantic cod (Gadus morhua): origins of the 'Codmother' trans-Atlantic vicariance, and mid-glacial population expansion. Genetics 2008, 108:381-389.
• [38]Møller D: Genetic differences between cod groups in the Lofoten area. Nature 1966, 212:824.
• [39]Jamieson A, Jones B: Two races of cod at Faroe. Heredity 1967, 22:610-612.
• [40]Lambert LA, Perri H, Halbrooks PJ, Mason AB: Evolution of the transferrin family: Conservation of residues associated with iron and anion binding. Comp Biochem Physiol B 2005, 142:129-141.
• [41]Zak O, I Aisen P, Crawley RW, Joannou CL, Patel KJ, Rafiq M, Evans RW: Iron release from recombinant N-lobe and mutants of human transferrin. Biochemistry 1995, 34:14428-14434.
• [42]Baker EN, Baker HM, Smith CA, Stebbins MR, Kahn M, Hellstrøm KE, Hellstrøm I: Human melanotransferrin (p97) has only one functional iron-binding site. FEBS 1992, 298:215-218.
• [43]Uppal R, lakshmi KV, Valentine AM: Isolation and characterization of the iron-binding properties of a primitive monolobal transferrin from Ciona intestinalis. J Biol Inorg Chem 2008, 13:873-885.
• [44]Denowan-Wright EM, Ramsey NB, McCormick CJ, Lazier CB, Wright JM: Nucleotide sequence of transferrin cDNAs and tissue-specific expression of the transferrin gene in Atlantic cod (Gadus morhua). Comp Biochem Physiol B 1996, 113:269-272.
• [45]Antunes A, Templeton AR, Guyomard R, Alexandrino P: The role of nuclear genes in intraspecific evolutionary inference: genealogy of the transferrin gene in the brown trout. Mol Biol Evol 2002, 19:1272-1287.
• [46]Gharbi K, Gautier A, Danzmann RG, Gharbi S, Sakamoto T, Høyheim B, Taggart JB, Cairney M, Powell R, Krieg F, Okamoto N, Ferguson MM, Holm LE, Guyomard R: A linkage map for brown trout (Salmo trutta): chromosome homeologies and comparative genome organization with other salmonid fish. Genetics 2006, 172:2405-2419.
• [47]Rozman T, Dovc P, Marić S, Kokalj-Vokac N, Erjavec-Skerget A, Rab P, Snoj A: Evidence for two transferrin loci in the Salmo trutta genome. Anim Genet 2008, 39:577-585.
• [48]Liu H, Takano T, Peatman E, Abernathy J, Wang S, Sha Z, Kucuktas H, Xu DH, Klesius P, Liu Z: Molecular characterization and gene expression of the channel catfish ferritin H subunit after bacterial infection and iron treatment. J Exp Zool A 2010, 313:359-368.
• [49]Yang F, Lum JB, McGill JR, Moore CM, Naylor SL, van Bragt PH, Baldwin WD, Bowman BH: Human transferrin: cDNA characterization and chromosomal localization. Proc Natl Acad Sci USA 1984, 81:2752-2756.
• [50]Baldwin GS: Comparison of transferrin sequences from different species. Comp Biochem Physiol B 1993, 106:203-218.
• [51]Jamroz RC, Gasdaska JR, Bradfield JY, Law JH: Transferrin in a cockroach: Molecular cloning, characterization, and suppresion by juvenile hormone. Proc Natl Acad Sci USA 1993, 90:1320-1324.
• [52]Williams J, Grace SA, Williams JM: Evolutionary significance of the renal excretion of transferrin half-molecule fragments. Biochem J 1982, 201:417-419.
• [53]Gaffney JP, Valentine AM: Contrasting synergistic anion effects in vanadium (V) binding to nicatransferrin versus human serum transferrin. Biochemistry 2009, 48:11609-11611.
• [54]Suryo Rahmanto Y, Dunn LL, Richardson DR: The melanoma tumor antigen, melanotransferrin (p97): a 25-year hallmark - from iron metabolism to tumorigenesis. Oncogene 2007, 26:6113-6124.
• [55]Dehal P, Boore JL: Two rounds of whole genome duplication in the ancestral vertebrate. PLOS Biology 2005, 3:e314.
• [56]Nakamasu K, Kawamoto T, Shen M, Gotoh O, Teramoto M, Noshiro M, Kato Y: Membrane-bound transferrin-like protein (MTf): structure, evolution and selective expression during chondrogenic differentiation of mouse embryonic cells. Biochim Biophys Acta 1999, 1447:258-264.
• [57]Lane RS: Transferrin-reticulocyte binding: evidence for the functional importance of transferrin conformation. British J Haematology 1972, 22:309-317.
• [58]Ford MJ: Effects of natural selection on patterns of DNA sequence variation at the transferrin, somatolactin, and p53 genes within and among chinook salmon (Oncorhynchus tshawytscha) populations. Mol Ecol 2000, 9:843-855.
• [59]Ford MJ, Thornton PJ, Park LK: Natural selection promotes divergence of transferrin among salmonid species. Mol Ecol 1999, 8:1055-1061.
• [60]Trinchella F, Parisi E, Scudiero R: Evolutionary analysis of the transferrin gene in Antarctic Notothenioidei: A history of adaptive evolution and functional divergence. Marine Genomics 2009, 1:95-101.
• [61]Nielsen EE, Wright PJ, Hemmer-Hansen J, Poulsen NA, Gibb IM, Meldrup D: Microgeographical population structure of cod Gadus morhua in the North Sea and west of Scotland: the role of sampling loci and individuals. Mar Ecol Prog Ser 2009, 376:213-225.
• [62]O'Leary DB, Coughlan J, Dillane E, McCarthy TV, Cross TF: Microsatellite varition in cod Gadus morhua throughout its geographic range. J Fish Biology C 2007, 70:310-335.
• [63]Sick K: Haemoglobin polymorphism of cod in the North Sea and the North Atlantic ocean. Hereditas 1965, 54:49-69.
• [64]Case RAJ, Hutchinson WF, Hauser L, Van Oosterhout C, Carvalho GR: Macro- and micro-geographic variation in pantophysin (PanI) allele frequencies in NE Atlantic cod Gadus morhua. Mar Ecol Prog Ser 2005, 301:267-278.
• [65]Sick K: Haemoglobin polymorphism of cod in the Baltic and the Danish Belt sea. Hereditas 1965, 54:19-48.
• [66]Nissling A, Westin L: Salinity requirements for successful spawning of Baltic and Belt Sea cod and the potential for cod stock interactions in the Baltic Sea. Mar Ecol Prog Ser 1997, 152:261-271.
• [67]Wojtczak M, Dietrich GJ, Irnazarow I, Jurecka P, Słowińska M, Ciereszko A: Polymorphism of transferrin of carp seminal plasma: relationship to blood transferrin and sperm motility characteristics. Comp Biochem Physiol B 2007, 148:426-31.
• [68]Rengmark AH, Lingaas F: Genomic structure of the Nile tilapia (Oreochromis niloticus) transferrin gene and a haplotype associated with saltwater tolerance. Aquaculture 2007, 272:146-155.
• [69]Bernatchez L, Landry C: MHC studies in nonmodel vertebrates: what have we learned about natural selection in 15 years? J Evol Biol 2003, 16:363-377.
• [70]Hedrick PW: Genetic polymorphism in Heterogeneous Environments: The age of genomics. Annu Rev Ecol Evol Syst 2006, 37:67-93.
• [71]Thisse C, Thisse B: High-resolution in situ hybridization to whole-mount zebrafish embryos. Nat Protoc 2008, 3:59-69.
• [72]Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997, 25:3389-3402.
• [73]Wally J, Halbrooks PJ, Vonrhein C, Rould MA, Everse SJ, Mason AB, Buchanan SK: The crystal structure of iron-free human serum transferrin provides insight into inter-lobe communication and receptor binding. J Biol Chem 2006, 281:24934-44.
• [74]Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG: ClustalW and ClustalX version 2. Bioinformatics 2007, 23:2947-2948.
• [75]Hirose M: The structural mechanism for iron uptake and release by transferrins. Biosci Biotechnol Biochem 2000, 64:1328-1336.
• [76]Sali A, Blundell TL: Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 1993, 234:779-815.
• [77]Luthy R, Bowie JU, Eisenberg D: Assessment of protein models with three-dimensional profiles. Nature 1992, 356:83-85.
• [78]Laskowski R, Rullmannn J, MacArthur M, Kaptein R, Thornton J: AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR. J Biomol NMR 1996, 8:477-486.
• [79]Wiederstein M, Sippl MJ: ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res 2007, 35:W407-W410.
• [80]Thompson J, Gibson T, Plewniak F, Jeanmougin F, Higgins D: The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 1997, 25:4876-4882.
• [81]Abascal F, Zardoya R, Posada D: ProtTest: selection of best-fit models of protein evolution. Bioinformatics 2005, 21:2104-2105.
• [82]Ronquist F, Huelsenbeck J: MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 2003, 19:1572-1574.
• [83]Stamatakis A: RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics 2006, 22:2688-2690.
• [84]Nei M, Gojobori T: Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 1986, 3:418-426.
• [85]Moen T, Delghandi M, Wesmajervi MS, Westgaard JI, Fjalestad KT: A SNP/microsatellite genetic linkage map of the Atlantic cod (Gadus morhua). Animal Genetics 2009, 40:993-996.
• [86]Tang K, Fu D, Julien D, Braun A, Cantor C, Köster H: Chip-based genotyping by mass spectrometry. Proc Natl Acad Sci USA 1999, 96:10016-10020.
• [87]Rousset F: Genepop'007: a complete reimplementation of the Genepop software for Windows and Linux. Mol Ecol Resources 2008, 8:103-106.