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

Øivind Andersen12*, Maria Cristina De Rosa3, Davide Pirolli3, Ave Tooming-Klunderud4, Petra E Petersen5 and Carl André6

Author affiliations

1 Nofima Marin, P. O. Box 5010, N-1430 Ås, Norway

2 Norwegian University of Life Sciences, P. O. Box 5003, N-1430 Ås, Norway

3 Institute of Chemistry of Molecular Recognition - CNR and Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, 00168 Rome, Italy

4 Centre for Ecological and Evolutionary Synthesis (CEES), Department of Biology, University of Oslo, P.O. Box 1066 Blindern, N-0316 Oslo, Norway

5 Aquaculture Research Station of the Faroes, FO-430 Hvalvík, Faroe Islands

6 Department of Marine Ecology-Tjärnö, Gothenburg University, S-45296 Strömstad, Sweden

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Citation and License

BMC Genetics 2011, 12:51  doi:10.1186/1471-2156-12-51

Published: 25 May 2011



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.


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.


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.

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