Genomic organization and gene expression of the multiple globins in Atlantic cod: conservation of globin-flanking genes in chordates infers the origin of the vertebrate globin clusters
© Wetten et al; licensee BioMed Central Ltd. 2010
Received: 18 June 2010
Accepted: 20 October 2010
Published: 20 October 2010
The vertebrate globin genes encoding the α- and β-subunits of the tetrameric hemoglobins are clustered at two unlinked loci. The highly conserved linear order of the genes flanking the hemoglobins provides a strong anchor for inferring common ancestry of the globin clusters. In fish, the number of α-β-linked globin genes varies considerably between different sublineages and seems to be related to prevailing physico-chemical conditions. Draft sequences of the Atlantic cod genome enabled us to determine the genomic organization of the globin repertoire in this marine species that copes with fluctuating environments of the temperate and Arctic regions.
The Atlantic cod genome was shown to contain 14 globin genes, including nine hemoglobin genes organized in two unlinked clusters designated β5-α1-β1-α4 and β3-β4-α2-α3-β2. The diverged cod hemoglobin genes displayed different expression levels in adult fish, and tetrameric hemoglobins with or without a Root effect were predicted. The novel finding of maternally inherited hemoglobin mRNAs is consistent with a potential role played by fish hemoglobins in the non-specific immune response. In silico analysis of the six teleost genomes available showed that the two α-β globin clusters are flanked by paralogs of five duplicated genes, in agreement with the proposed teleost-specific duplication of the ancestral vertebrate globin cluster. Screening the genome of extant urochordate and cephalochordate species for conserved globin-flanking genes revealed linkage of RHBDF1, MPG and ARHGAP17 to globin genes in the tunicate Ciona intestinalis, while these genes together with LCMT are closely positioned in amphioxus (Branchiostoma floridae), but seem to be unlinked to the multiple globin genes identified in this species.
The plasticity of Atlantic cod to variable environmental conditions probably involves the expression of multiple globins with potentially different properties. The interspecific difference in number of fish hemoglobin genes contrasts with the highly conserved synteny of the flanking genes. The proximity of globin-flanking genes in the tunicate and amphioxus genomes resembles the RHBDF1-MPG-α-globin-ARHGAP17-LCMT linked genes in man and chicken. We hypothesize that the fusion of the three chordate linkage groups 3, 15 and 17 more than 800 MYA led to the ancestral vertebrate globin cluster during a geological period of increased atmospheric oxygen content.
Hemoglobin plays a critical role in both terrestrial and aquatic animals by transporting oxygen from the respiratory surface to the inner organs. The functional complexity and evolutionary adaptation of this heme-containing molecule to different environments has therefore attracted researchers for more than a half-century. In jawed vertebrates, or gnathostomes, the hemoglobin tetramer consists of two pairs of α- and β-globins, which probably arose by duplication of a single primordial globin gene about 500-570 million years ago (MYA) [1, 2]. Whereas α- and β-globin genes are juxtaposed in teleost fish, birds and mammals are characterized by unlinked clusters of α- and β-globin genes, which in mammals are arranged in the order of their expression during ontogeny [3, 4]. Based on the conservation of the globin-flanking genes, including MPG and c16orf35, all gnathostomes examined share a common globin cluster referred to as the MC locus  corresponding to the α-globin cluster in placental mammals and chicken. Silencing of the β genes in the ancestral MC-α-β cluster has apparently also occurred in non-amniotic species, such as pufferfish, whereas a single β-like ϖ-globin is retained in the α cluster of marsupials and monotremes [6–8]. The teleost-specific genome duplication event 350-400 MYA probably gave rise to the second fish α-β globin cluster flanked by ARHGAP17, LCMT and AQP8 [5, 8]. It should be noted that this LA locus lacks globin genes in tetrapods, but is positioned on the α-containing chromosome 16 and 14 in man and chicken, respectively . The amniotic β-globin cluster is thought to have originated from the transposition of a β gene copy into a region of olfactory receptor genes in their ancestor [8–10].
In contrast to the linked α-β globin pairs identified in Xenopus, the fish α-β pairs are commonly organized head-to-head or tail-to-tail with respect to transcriptional polarity [11–16]. These configurations probably arose from an inversion of one of the paired α-β genes in an ancestral ray-finned fish, thus resembling the reported case of gene inversion within the human β-globin cluster . The structural and functional diversity of the multiple hemoglobins in teleosts strongly indicates that they have experienced a major evolutionary pressure to execute their oxygen-transporting function under highly variable physico-chemical conditions [18–20]. The selective forces have apparently resulted in the loss of hemoglobin genes in the white-blooded Antarctic icefishes (Channichthyidae) to reduce the blood viscosity at stable subzero temperatures [21–23].
The genomic organization of the fish α-β globin clusters has only been investigated in the model species pufferfish, zebrafish and medaka [5, 6, 8, 10, 15, 24]. Atlantic cod is a marine cold water species being widely distributed from the sea surface to depths of 600 m in the Arctic and temperate regions of the North Atlantic Ocean, including the low saline Baltic Sea. Adaptation of the different cod populations to the varying physico-chemical conditions seems to involve hemoglobins with highly pH-sensitive oxygen affinities (Root effect) to adjust the swimming bladder to variable pressure during vertical migrations [25, 26], together with the novel feature of expressing polymorphic variants with different oxygen-binding properties . A variable number of cod hemoglobin genes and allelic variants have been reported in Norwegian, Icelandic and Canadian populations [27–29]. Here, we screened the draft cod genome  and identified nine α- and β-globin genes, which are organized in two unlinked clusters flanked by highly conserved syntenic regions. We document close linkage between the conserved globin-flanking genes in extant cephalochordate and urochordate species, and hypothesize that the fusion of three chordate chromosomes formed the ancestral vertebrate globin cluster more than 800 MYA.
Identification of cod globin clusters
Cod MC locus
Cod LA locus
Other cod globin genes
Five additional globin genes encoding myoglobin, neuroglobin, globin-X and two cytoglobins were identified in the cod genome (Figure 2). The gene encoding the predicted cod myoglobin of 145 aa is organized as the α-β globins, while neuroglobin and globin-X of 159 and 197 aa, respectively, are encoded by four and five exons. The three exons of the cytoglobin-2 gene encode a protein of 202 aa, while the draft genome sequences contained only a partial cytoglobin-1 gene. The four α-globins are less similar (35-67% identity) than the five β-globins (57-99%) of which β2, β3 and β4 show high sequence identity. The α-globins share only 25-33% identity with the β-globins, compared to sequence identities of about 20% between the cod α-β globins and the other globins, except for the very low similarity with globin-X. Despite this low overall identity, highly conserved positions were identified throughout the aligned sequences, including human β-globin (Figure 2). Rare mutations in almost all these positions have been reported to affect the functionality of human hemoglobin , and suggest the importance of these residues for the proper structure and/or function of different oxygen-binding molecules in diverse vertebrate species.
Globin gene mapping and expression
The cod α-β globin clusters were mapped to different linkage groups by genotyping multiple single nucleotide polymorphic (SNP) markers, including the globin SNPs underlying the Metβ1Val and Thrα2Ile polymorphisms . The segregation of the SNPs in full-sib cod families localized the MC and LA loci to linkage groups 17 and 16, respectively, among the total of 24 linkage groups .
The Atlantic cod genome was shown to harbor altogether nine α- and β-globin genes organized in two unlinked clusters similar to the other teleost genomes available. The expression of many hemoglobin genes in adult cod is consistent with the multiple tetrameric hemoglobin types and subtypes identified by gel electrophoresis of blood proteins [33, 34]. The cod hemoglobin repertoire is further extended by the polymorphic α1, β1, β3 and β4 globins [27, 29] of which the functionally different variants of β1 are differentially distributed in cod populations [27, 35, 36]. The dominant expression of α1, α2, β1 and β2 in adult fish is in agreement with the isolation of three major tetramers designated Hb1, Hb2 and Hb3, which comprise different combinations of these four subunits . The tetrameric Hb3 (α1-α1-β2-β2) was shown to exhibit a marked Root effect of importance for the delivery of oxygen to the swim bladder for neutral buoyancy and to the retina for enhanced visual acuity via the highly specialized vascular structures [25, 38]. The structural basis for this extreme acid-induced reduction in oxygen affinity is far from understood, but the putative key residues, including Asp95α, Asp99β and Asp101β [39, 40], are conserved in the cod hemoglobins, except for β1 and α3. We therefore suggest that the β1-containing Hb1 tetramer (α1-α1-β1-β1) has no Root effect and might function as an emergency oxygen supplier when fish exercise vigorously.
The detection of hemoglobin mRNAs in unfertilized cod eggs is the first evidence of maternally inherited α-β globins, while Vlecken et al.  recently reported maternal transfer of myoglobin mRNA in zebrafish. The function of these oxygen-binding molecules in the early fish embryo is uncertain, as aerobic processes have been shown to continue in the zebrafish embryo after functional ablation of hemoglobin . Hemoglobin-derived antimicrobial peptides expressed in the fish epithelium have been suggested to play a significant role in the non-specific immune response , together with maternally transferred transcripts encoding lysozyme and cathelicidin . The very low embryonic expression of globin genes is consistent with the transparent hemolymph flowing through the heart, which starts contracting after embryogenesis is two-thirds completed . Thus, the early larval expression of hemoglobins probably represents the initial stage of hemoglobin oxygen binding and coincides with gill development. The embryonic expression of β5 and the dominant mRNA levels of α4 at hatching are in agreement with the phylogenetic analysis grouping these genes together with other fish globins expressed in embryonic stages .
In contrast to the low number of globin genes reported in Antarctic teleosts , the adaptation of Atlantic cod to fluctuating environmental conditions probably involved the evolution of multiple globins with potentially different oxygen binding properties. The unlinked globin pairs α1-β1 and α2-β2 are abundantly expressed in the adult fish and form three major hemoglobin tetramers with different Root effect. The identification of paralogous genes in the flanking regions of the two globin clusters in diverse teleosts supports the proposed teleost-specific duplication of the vertebrate globin cluster. Based on the conserved synteny of globin-flanking genes in extant urochordate and cephalochordate species, we hypothesize that the ancestral globin cluster contained both the MC and LA loci, and was formed by the fusion of three chordate chromosomes. We propose that these chromosomal rearrangements facilitated the transcriptional regulation of globin synthesis to cope with increased atmospheric oxygen content about 850 MYA. Thus, these regulatory changes probably preceded the convergent evolution of different ancestral globins to function as erythroid-specific oxygen transporting hemoglobins.
Identification of globin clusters
PCR primers for amplification of cod α1-β1 gene pair and for screening BAC library.
Sequence (5' to 3')
BAC library screening
Primers for real-time qPCR, amplification efficiency (%) and amplicon size (bp).
Sequence (5' to 3')
β1 allele A
β1 allele B
Cod genome BLAST
The Atlantic cod genome project (http://www.codgenome.no) is based on the genome sequences of the north-east Arctic cod population. Scaffold sequences harboring globin genes were identified among the assemblies of the cod genome project  using the BLAST search tool at http://www.bioportal.uio.no. Annotation of genes located on the scaffolds was completed based on results from TBLASTN searches of known protein sequences from related species, using the bioinformatics software CLC genomics workbench (CLC bio).
Chordate genome BLAST
Conserved globin and globin-flanking genes were identified in cephalochordate and urochordate species by BLAST searching the genomes of Branchiostoma floridae (version 1.0, http://genome.jgi-psf.org/Brafl1/Brafl1.home.html) and Ciona intestinalis (release 43, http://www.ensembl.org/Ciona_intestinalis/Info/Index).
Spleen and blood were sampled from juvenile (n = 5) and adult (n = 12) fish kept at the National Cod Breeding Centre (Kraknes, Tromsø, Norway) and the University of Bergen, respectively. Sexually mature fish were hand-stripped, and eggs were fertilized in vitro. The incubation of embryos and feeding of larvae were carried out as described . Sampling of unfertilized eggs, fertilized eggs and larvae was performed during 10 weeks. All samples were rapidly submerged in RNAlater (Ambion, Austin, TX, USA) and incubated at 4°C overnight, then stored at -20°C.
RNA isolation and cDNA synthesis
5-10 eggs/embryos or 3-5 larvae were pooled and homogenized in 1.5 ml microcentrifuge tubes containing lysis buffer (Qiagen RNeasy mini kit) using a plastic pestle. After centrifugation through a QiaShredder column (Qiagen, Hilden, Germany), RNA was isolated according to the manufacturer's protocol (Qiagen RNeasy mini kit), and followed by the recommended on-column DNase treatment. The Qiagen RNeasy mini kit was also used for the spleen and blood samples from juvenile and adult fish, respectively. cDNA was synthesized from 1 μg total RNA using TaqMan® Reverse Transcription Reagents (Applied Biosystems) and oligo-dT primer in 20 μl reactions using the conditions of: 25°C for 10 min, 48°C for 30 min and 95°C for 5 min. Primers used for real-time qPCR were adopted from Borza et al.  for the globins, while ubiquitin primers were taken from Olsvik et al.  (Table 2). For the β1 gene, two allele-specific primer sets were used on all samples, and relative expression was calculated dependent on the actual genotype of each sample. Ten-fold dilution series were prepared to generate standard curves, and PCR efficiencies and relative quantification results were calculated according to Ståhlberg et al.  using ubiquitin as the reference transcript . Cycling parameters were 50°C for 2 min, 95°C for 10 min, 40 cycles of 95°C for 15 sec, 61°C for 1 min, including a final dissociation stage to yield melting curves. Reactions of 25 μl consisted of 12.5 μl 2× Power SYBR®Green PCR Master Mix (Applied Biosystems), 0.5 μl each of sense and antisense primers (10 μM) and 11.5 μl of 50× diluted cDNA.
List of abbreviations
Rho GTPase activating protein 17
rhomboid 5 homolog 1
leucine carboxyl methyltransferase
human chromosome 16 open reading frame 35
DNA-directed RNA polymerase III subunit RPC10
mahogunin Ring Finger 1
dedicator of cytokinesis
ankyrin repeat domain
fork head J1
fluorescence in situ hybridization
chordate linkage group
days post fertilization
days post hatching.
We thank Carl Andrè and two anonymous reviewers for helpful comments and suggestions. This work was funded by grants to Ø.A., A.N. and K.S.J. from the Norwegian Research Council and by a PhD stipend to O.F.W financed by The Norwegian Ministry of Education and Research.
- Goodman M, Moore GW, Matsuda G: Darwinian evolution in the genealogy of haemoglobin. Nature. 1975, 253: 603-608. 10.1038/253603a0.View ArticlePubMedGoogle Scholar
- Jeffreys AJ, Wilson V, Wood D, Simons JP, Kay RM, Williams JG: Linkage of adult α- and β-globin genes in X. laevis and gene duplication by tetraploidization. Cell. 1980, 21: 555-64. 10.1016/0092-8674(80)90493-6.View ArticlePubMedGoogle Scholar
- Efstratiadis A, Posakony JW, Maniatis T, Lawn RM, O'Connell C, Spritz RA, Deriel JK, Forget BG, Weissman SM, Slightom JL, Blechl AE, Smithies O, Baralle FE, Shoulders CC, Proudfoot NJ: The structure and evolution of the human β-globin gene family. Cell. 1980, 21: 653-668. 10.1016/0092-8674(80)90429-8.View ArticlePubMedGoogle Scholar
- Lauer J, Shen CK, Maniatis T: The chromosomal arrangement of human alpha-like globin genes: sequence homology and alpha-globin gene deletions. Cell. 1980, 20: 119-130. 10.1016/0092-8674(80)90240-8.View ArticlePubMedGoogle Scholar
- Hardison RC: Globin genes on the move. J Biol. 2008, 7: 35-10.1186/jbiol92.PubMed CentralView ArticlePubMedGoogle Scholar
- Flint J, Tufarelli C, Peden J, Clark K, Daniels RJ, Hardison R, Miller W, Philipsen S, Tan-Un KC, McMorrow T, Frampton J, Alter BP, Frischauf AM, Higgs DR: Comparative genome analysis delimits a chromosomal domain and identifies key regulatory elements in the alpha globin cluster. Hum Mol Genet. 2001, 10: 371-382. 10.1093/hmg/10.4.371.View ArticlePubMedGoogle Scholar
- Wheeler D, Hope RM, Cooper SJ, Gooley AA, Holland RA: Linkage of the beta-like omega-globin gene to alpha-like globin genes in an Australian marsupial supports the chromosome duplication model for separation of globin gene clusters. J Mol Evol. 2004, 58: 642-52. 10.1007/s00239-004-2584-0.View ArticlePubMedGoogle Scholar
- Patel VS, Cooper SJ, Deakin JE, Fulton B, Graves T, Warren WC, Wilson RK, Graves JA: Platypus globin genes and flanking loci suggest a new insertional model for beta-globin evolution in birds and mammals. BMC Biol. 2008, 6: 34-10.1186/1741-7007-6-34.PubMed CentralView ArticlePubMedGoogle Scholar
- Bulger M, van Doorninck JH, Saitoh N, Telling A, Farrell C, Bender MA, Felsenfeld G, Axel R, Groudine M: Conservation of sequence and structure flanking the mouse and human beta-globin loci: the beta-globin genes are embedded within an array of odorant receptor genes. Proc Natl Acad Sci USA. 1999, 96: 5129-5134. 10.1073/pnas.96.9.5129.PubMed CentralView ArticlePubMedGoogle Scholar
- Gillemans N, McMorrow T, Tewari R, Wai AW, Burgtorf C, Drabek D, Ventress N, Langeveld A, Higgs D, Tan-Un K, Grosveld F, Philipsen S: Functional and comparative analysis of globin loci in pufferfish and humans. Blood. 2003, 101: 2842-2849. 10.1182/blood-2002-09-2850.View ArticlePubMedGoogle Scholar
- Wagner A, Deryckere F, McMorrow T, Gannon F: Tail-to-tail orientation of the Atlantic salmon alpha- and beta-globin genes. J Mol Evol. 1994, 38: 28-35. 10.1007/BF00175492.View ArticlePubMedGoogle Scholar
- McMorrow T, Wagner A, Deryckere F, Gannon F: Structural organization and sequence analysis of the globin locus in Atlantic salmon. DNA and Cell Biol. 1996, 15: 407-414. 10.1089/dna.1996.15.407.View ArticleGoogle Scholar
- Miyata M, Aoki T: Head-to-head linkage of carp α- and β-globin genes. Biochim Biophys Acta. 1997, 1354: 127-133.View ArticlePubMedGoogle Scholar
- Lau DT, Saeed-Kothe A, Parker SK, Detrich HW: Adaptive evolution of gene expression in Antarctic fishes: Divergent transcription of the 5'-to-5' linked adult α1- and β-globin genes of the Antarctic teleost Notothenia coriiceps is controlled by dual promoters and intergenic enhancers. Amer Zool. 2001, 41: 113-132. 10.1668/0003-1569(2001)041[0113:AEOGEI]2.0.CO;2.Google Scholar
- Maruyama K, Yasumasu S, Naruse K, Mitani H, Shima A, Iuchi I: Genomic organization and developmental expression of globin genes in the teleost Oryzias latipes. Gene. 2004, 335: 89-100. 10.1016/j.gene.2004.03.007.View ArticlePubMedGoogle Scholar
- Fuchs A, Burmester T, Hankeln T: The amphibian globin gene repertoire as revealed by the Xenopus genome. Cytogenet Genome Res. 2006, 112: 296-306. 10.1159/000089884.View ArticlePubMedGoogle Scholar
- Jennings MW, Jones RW, Wood WG, Weatherall DJ: Analysis of an inversion within the human beta globin gene cluster. Nucl Acids Res. 1985, 13: 2897-2906. 10.1093/nar/13.8.2897.PubMed CentralView ArticlePubMedGoogle Scholar
- Perutz MF: Species adaptation in a protein molecule. Mol Biol Evol. 1983, 1: 1-28.PubMedGoogle Scholar
- Weber RE, Fago A: Functional adaptation and its molecular basis in vertebrate hemoglobins, neuroglobins and cytoglobins. Resp Physiol Neurobiol. 2004, 144: 141-159. 10.1016/j.resp.2004.04.018.View ArticleGoogle Scholar
- Weber RE: Adaptations for oxygen transport: lessons from fish hemoglobins. Hemoglobin Function in Vertebrates, Molecular Adaptation in Extreme and Temperate Environments. Edited by: Di Prisco G, Giardina B, Weber RE. 2000, Milano: Springer-Verlag, 23-37.View ArticleGoogle Scholar
- Ruud JT: Vertebrates without erythrocytes and blood pigment. Nature. 1954, 173: 848-850. 10.1038/173848a0.View ArticlePubMedGoogle Scholar
- Bargelloni L, Marcato S, Patarnello T: Antarctic fish hemoglobins: Evidence for adaptive evolution at subzero temperature. Proc Natl Acad Sci USA. 1998, 95: 8670-8675. 10.1073/pnas.95.15.8670.PubMed CentralView ArticlePubMedGoogle Scholar
- di Prisco G, Ennio C, Parker SK, Detrich HW: Tracking the evolutionary loss of hemoglobin expression by the white-blooded Antarctic icefishes. Gene. 2002, 295: 185-191. 10.1016/S0378-1119(02)00691-1.View ArticlePubMedGoogle Scholar
- Maruyama K, Yasumasu S, Iuchi I: Evolution of globin genes of the medaka Oryzias latipes (Euteleostei; Beloniformes; Oryziinae). Mech Dev. 2004, 121: 753-769. 10.1016/j.mod.2004.03.035.View ArticlePubMedGoogle Scholar
- Berenbrink M, Koldkjær P, Kepp O, Cossins AR: Evolution of oxygen secretion in fishes and the emergence of a complex physiological system. Science. 2005, 307: 1752-1757. 10.1126/science.1107793.View ArticlePubMedGoogle Scholar
- van der Kooij J, Righton D, Strand E, Michalsen K, Thorsteinsson V, Svedäng H, Neat FC, Neuenfeldt S: Life under pressure: insights from electronic data-storage tags into cod swimbladder function. ICES J Mar Sci. 2007, 64: 1293-1301. 10.1093/icesjms/fsm119.View ArticleGoogle Scholar
- Andersen Ø, Wetten OF, De Rosa MC, Andre C, Carelli Alinovi C, Colafranceschi M, Brix O, Colosimo A: Hemoglobin polymorphisms affect the oxygen binding properties in Atlantic cod populations. Proc Royal Soc B. 2009, 276: 833-841. 10.1098/rspb.2008.1529.View ArticleGoogle Scholar
- Halldorsdottir K, Arnason E: Organization of a β and α globin gene set in the teleost Atlantic cod, Gadus morhua. Biochem Genet. 2009, 47: 817-830. 10.1007/s10528-009-9280-0.View ArticlePubMedGoogle Scholar
- Borza T, Stone C, Gamperl AK, Bowman S: Atlantic cod (Gadus morhua) hemoglobin genes: multiplicity and polymorphism. BMC Genetics. 2009, 10: 51-10.1186/1471-2156-10-51.PubMed CentralView ArticlePubMedGoogle Scholar
- Johansen SD, Coucheron DH, Andreassen M, Karlsen BO, Furmanek T, Jorgensen TE, Emblem A, Breines R, Nordeide JT, Moum T, Nederbragt AJ, Stenseth NC, Jakobsen KS: Large-scale sequence analyses of Atlantic cod. New Biotechnology. 2009, 25: 263-271. 10.1016/j.nbt.2009.03.014.View ArticlePubMedGoogle Scholar
- Hardison RC, Chui DH, Riemer C, Giardine B, Lehväslaiho H, Wajcman H, Miller W: Databases of human hemoglobin variants and other resources at the globin gene server. Hemoglobin. 2001, 25: 183-190. 10.1081/HEM-100104027.View ArticlePubMedGoogle Scholar
- 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. 10.1111/j.1365-2052.2009.01938.x.View ArticlePubMedGoogle Scholar
- Fyhn UEH, Brix O, Nævdal G, Johansen T: New variants of the haemoglobins of Atlantic cod: a tool for discriminating between coastal and Arctic cod populations. ICES Mar Sci Symp. 1994, 198: 666-670.Google Scholar
- Husebø Å, Imsland AK, Nævdal G: Haemoglobin variation in cod: a description of new variants and their geographical distribution. Sarsia. 2004, 90: 1-11.Google Scholar
- Karpov AK, Novikov GG: The hemoglobin aloforms in cod (Gadus morhua L.), their functional characteristics and distribution in the populations. J Ichthyol. 1980, 6: 45-50.Google Scholar
- Brix O, Thorkildsen S, Colosimo A: Temperature acclimation modulates the oxygen binding properties of the Atlantic cod (Gadus morhua L.) genotypes-HbI*1/1, HbI*1/2, and HbI*2/2 by changing the concentrations of their major hemoglobin components (results from growth studies at different temperatures). Comp Biochem Physiol. 2004, 138A: 241-251.View ArticleGoogle Scholar
- Verde C, Balesrieri M, de Pascale D, Pagnozzi D, Lecointre G, di Prisco G: The oxygen transport system in three species of the boreal fish family Gadidae. J Biol Chem. 2006, 281: 22073-22084. 10.1074/jbc.M513080200.View ArticlePubMedGoogle Scholar
- Scholander PF, van Dam L, Enns T: The source of oxygen secreted into the swimbladder of cod. J Cell Comp Physiol. 2005, 48: 517-522. 10.1002/jcp.1030480310.View ArticleGoogle Scholar
- Yokoyama T, Chong KT, Miyazaki G, Morimoto H, Shih DT, Unzai S, Tame JR, Park SY: Novel mechanisms of pH sensitivity in tuna hemoglobin: a structural explanation of the Root effect. J Biol Chem. 2004, 279: 28632-29640. 10.1074/jbc.M401740200.View ArticlePubMedGoogle Scholar
- Mazzarella L, Vergara A, Vitagliano L, Merlino A, Bonomi G, Scala S, Verde C, di Prisco G: High resolution crystal structure of deoxy hemoglobin from Trematomus bernacchii at different pH values: the role of histidine residues in modulating the strength of the root effect. Proteins. 2006, 65: 490-498. 10.1002/prot.21114.View ArticlePubMedGoogle Scholar
- Vlecken DH, Teserink J, Ott EB, Sakalis PA, Jaspers RT, Bagowski CP: A critical role for myoglobin in zebrafish development. I J Dev Biol. 2009, 53: 517-524. 10.1387/ijdb.082651dv.View ArticleGoogle Scholar
- Pelster B, Burggren WW: Disruption of hemoglobin oxygen transport does not impact oxygen-dependent physiological processes in developing embryos of zebrafish (Danio rerio). Circulation Res. 1996, 79: 358-262.View ArticlePubMedGoogle Scholar
- Ullal AJ, Litaker RW, Noga EJ: Antimicrobial peptides derived from haemoglobin are expressed in epithelium of channel catfish (Ictalurus punctatus, Rafinesque). Dev Comp Immun. 2008, 32: 1301-1312. 10.1016/j.dci.2008.04.005.View ArticleGoogle Scholar
- Seppola M, Johnsen H, Mennen S, Myrnes B, Tveiten H: Maternal transfer and transcriptional onset of immune genes during ontogenesis in Atlantic cod. Dev Comp Immunol. 2009, 33: 1205-1211. 10.1016/j.dci.2009.06.013.View ArticlePubMedGoogle Scholar
- Hall TE, Smoth P, Johnston IA: Stages of embryonic development in the Atlantic cod Gadus morhua. J Morphology. 2004, 259: 255-270. 10.1002/jmor.10222.View ArticleGoogle Scholar
- Cocca E, Ratnayake-Lecamwasam M, Parker SK, Camardella L, Ciaramella M, di Prisco G, Detrich HW: Genomic remnants of alpha-globin genes in the hemoglobinless antarctic icefishes. Proc Natl Acad Sci USA. 1995, 92: 1817-21. 10.1073/pnas.92.6.1817.PubMed CentralView ArticlePubMedGoogle Scholar
- di Prisco G, Eastman JT, Giordano D, Parisi E, Verde C: Biogeography and adaptation of Notothenioid fish: hemoglobin function and globin-gene evolution. Gene. 2007, 398: 143-155. 10.1016/j.gene.2007.02.047.View ArticlePubMedGoogle Scholar
- Kock KH: Antarctic icefishes (Channichthyidae): a unique family of fishes. A review, Part II. Polar Biol. 2005, 28: 897-909. 10.1007/s00300-005-0020-6.View ArticleGoogle Scholar
- Colafranceschi M, Giuliani A, Andersen Ø, Brix O, De Rosa MC, Giardina B, Colosimo A: Hydrophobicity patterns and biological adaptation: an exemplary case from fish hemoglobins. OMICS. 2010, 14: 275-281. 10.1089/omi.2010.0007.View ArticlePubMedGoogle Scholar
- Kasahara M, Naruse K, Sasaki S, Nakatani Y, Qu W, Ahsan B, Yamada T, Nagayasu Y, Doi K, Kasai Y, Jindo T, Kobayashi D, Shimada A, Toyoda A, Kuroki Y, Fujiyama A, Sasaki T, Shimizu A, Asakawa S, Shimizu N, Hashimoto S, Yang J, Lee Y, Matsushima K, Sugano S, Sakaizumi M, Narita T, Ohishi K, Haga S, Ohta F, Nomoto H, Nogata K, Morishita T, Endo T, Shin-I T, Takeda H, Morishita S, Kohara Y: The medaka draft genome and insights into vertebrate genome evolution. Nature. 2007, 447: 714-719. 10.1038/nature05846.View ArticlePubMedGoogle Scholar
- Naruse K, Tanaka M, Mita K, Shima A, Postlethwaite J, Mitani H: A medaka gene map: the trace of ancestral vertebrate proto-chromosomes revealed by comparative gene mapping. Genome Res. 2004, 14: 820-828. 10.1101/gr.2004004.PubMed CentralView ArticlePubMedGoogle Scholar
- Ebner B, Burmester T, Hankeln T: Globin genes are present in Ciona intestinalis. Mol Biol Evol. 2003, 20: 1521-1525. 10.1093/molbev/msg164.View ArticlePubMedGoogle Scholar
- Putnam NH, Butts T, Ferrier DE, Furlong RF, Hellsten U, Kawashima T, Robinson-Rechavi M, Shoguchi E, Terry A, Yu JK, Benito-Gutiérrez EL, Dubchak I, Garcia-Fernàndez J, Gibson-Brown JJ, Grigoriev IV, Horton AC, de Jong PJ, Jurka J, Kapitonov VV, Kohara Y, Kuroki Y, Lindquist E, Lucas S, Osoegawa K, Pennacchio LA, Salamov AA, Satou Y, Sauka-Spengler T, Schmutz J, Shin-I T, Toyoda A, Bronner-Fraser M, Fujiyama A, Holland LZ, Holland PW, Satoh N, Rokhsar DSP: The amphioxus genome and evolution of the chordate karyotype. Nature. 2008, 453: 1064-1072. 10.1038/nature06967.View ArticlePubMedGoogle Scholar
- Blair JE, Hedges SB: Molecular phylogeny and divergence times of deuterostome animals. Mol Biol Evol. 2005, 22: 2275-2284. 10.1093/molbev/msi225.View ArticlePubMedGoogle Scholar
- Holland H: The oxygenation of the atmosphere and oceans. Phil Trans Roy Soc B. 2006, 361: 903-910. 10.1098/rstb.2006.1838.View ArticleGoogle Scholar
- Bailly X, Leroy R, Carney S, Collin O, Zal F, Toulmond A, Jollivet D: The loss of the hemoglobin H2S-binding function in annelids from sulfide-free habitats reveals molecular adaptation driven by Darwinian positive selection. Proc Natl Acad Sci USA. 2003, 100: 5885-5890. 10.1073/pnas.1037686100.PubMed CentralView ArticlePubMedGoogle Scholar
- Hoffmann FG, Opazo JC, Storz JF: Gene cooption and convergent evolution of oxygen transport hemoglobins in jawed and jawless vertebrates. Proc Natl Acad Sci USA. 2010, 107: 14274-14279. 10.1073/pnas.1006756107.PubMed CentralView ArticlePubMedGoogle Scholar
- Hardison R: Hemoglobins from bacteria to man: evolution of different patterns of gene expression. J Exp Biol. 1998, 201: 1099-1117.PubMedGoogle Scholar
- Zhou GL, Xin L, Song W, Di LJ, Liu G, Wu XS, Liu DP, Liang CC: Active chromatin hub of the mouse alpha-globin locus forms in a transcription factory of clustered housekeeping genes. Mol Cell Biol. 2006, 26: 5096-5105. 10.1128/MCB.02454-05.PubMed CentralView ArticlePubMedGoogle Scholar
- Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA, Berka J, Braverman MS, Chen YJ, Chen Z, Dewell SB, Du L, Fierro JM, Gomes XV, Godwin BC, He W, Helgesen S, Ho CH, Irzyk GP, Jando SC, Alenquer ML, Jarvie TP, Jirage KB, Kim JB, Knight JR, Lanza JR, Leamon JH, Lefkowitz SM, Lei M, Li J, Lohman KL, Lu H, Makhijani VB, McDade KE, McKenna MP, Myers EW, Nickerson E, Nobile JR, Plant R, Puc BP, Ronan MT, Roth GT, Sarkis GJ, Simons JF, Simpson JW, Srinivasan M, Tartaro KR, Tomasz A, Vogt KA, Volkmer GA, Wang SH, Wang Y, Weiner MP, Yu P, Begley RF, Rothberg JM: Genome sequencing in microfabricated high-density picolitre reactors. Nature. 2005, 437: 376-380.PubMed CentralPubMedGoogle Scholar
- Olsvik PA, Søfteland L, Lie KK: Selection of reference genes for qRT-PCR examination of wild populations of Atlantic cod Gadus morhua. BMC Res Notes. 2008, 1: 47-10.1186/1756-0500-1-47.PubMed CentralView ArticlePubMedGoogle Scholar
- Ståhlberg A, Åman P, Ridell B, Mostad P, Kubista M: Quantitative real-time PCR method for detection of B-lymphocyte monoclonality by comparison of κ and λ immunoglobulin light chain expression. Clin Chem. 2003, 49: 51-59. 10.1373/49.1.51.View ArticlePubMedGoogle Scholar
- Sæle Ø, Nordgreen A, Hamre K, Olsvik PA: Evaluation of candidate reference genes in Q-PCR studies of Atlantic cod (Gadus morhua) ontogeny, with emphasis on the gastrointestinal tract. Comp Biochem Physiol B. 2009, 152: 94-101. 10.1016/j.cbpb.2008.10.002.View ArticlePubMedGoogle Scholar
- Azuma Y, Kumazawa Y, Miya M, Mabuchi K, Nishida M: Mitogenomic evaluation of the historical biogeography of cichlids toward reliable dating of teleostean divergences. BMC Evol Biol. 2008, 8: 215-10.1186/1471-2148-8-215.PubMed CentralView ArticlePubMedGoogle Scholar
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