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

Abstract

BackgroundThe 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.ResultsThe 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.ConclusionsThe 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.

Characterization of the gilthead seabream (Sparus aurata L.) transferrin gene: Genomic structure, constitutive expression and SNP variation

“…A greater number of cSNPs should be found from sequence alignment of individuals from populations subjected to different environmental conditions, showing a local adaptation to different environments. In fact, recently, by comparison of cDNA sequences from Northeast and Northwest Atlantic cod populations, Andersen et al [46] describe 22 SNPs in Tf1,causing the replacement of 16 amino acids, of which 8 affect to surface residues. The authors suggest that this multiple surface residue changes, as a result of an evolutionary competition for transferrin-bound iron between the host and invading pathogens.…”

Phylogenetic Analyses Uncover a Novel Clade of Transferrin in Nonmammalian Vertebrates

“…Positive selection in fish transferrin has been suggested to be driven by its competition for iron with proteins of pathogenic bacteria (Ford et al 1999). Consistent with the fact that the proteins involved in defence mechanisms have a high probability to undergo positive selection, lactoferrin in mammals and fish transferrin genes were expected to function specifically in defence mechanisms (Ford 2001; Yang 2006; Liang and Jiang 2010; Andersen et al 2011). …”

“…In contrast to the other transferrin proteins that have two iron-binding sites, melanotransferrin seems to contain a single one, and it is as yet unclear whether it transports iron (Sekyere and Richardson 2000). Otolith matrix protein-1, which has only been found in fish so far, represents the only monolobal transferrin in vertebrate (Andersen et al 2011). …”

“…In fish, positive selection has been suggested to occur in transferrin members of salmonid species (Ford et al 1999; Ford 2001). More recently, a study by Andersen et al (2011) showed a highly divergent allele frequency among G ad . morhua populations, which suggest the action of positive selection.…”

“…In addition, previous evolutionary analyses have suggested the action of positive selection in different transferrin proteins, which was interpreted as important for facilitating adaptation to the environment and pathogenic infections (Ellis 2001; Lambert, Perri, Meehan 2005; Andersen et al 2011). These include the identification of footprints of positive selection in mammalian lactoferrin, which was hypothesized to result from a genetic arm race (Liang and Jiang 2010).…”