Natural history of SLC11 genes in vertebrates: tales from the fish world

Jonathan M Wilson,João V Neves,Pedro Ns Rodrigues,L Filipe C Castro,Richard Reinhardt,Heiner Kuhl

doi:10.1186/1471-2148-11-106

Jonathan M Wilson, João V Neves + Show 4 more

Open Access

https://doi.org/10.1186/1471-2148-11-106

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Abstract

BackgroundThe SLC11A1/Nramp1 and SLC11A2/Nramp2 genes belong to the SLC11/Nramp family of transmembrane divalent metal transporters, with SLC11A1 being associated with resistance to pathogens and SLC11A2 involved in intestinal iron uptake and transferrin-bound iron transport. Both members of the SLC11 gene family have been clearly identified in tetrapods; however SLC11A1 has never been documented in teleost fish and is believed to have been lost in this lineage during early vertebrate evolution. In the present work we characterized the SLC11 genes in teleosts and evaluated if the roles attributed to mammalian SLC11 genes are assured by other fish specific SLC11 gene members.ResultsTwo different SLC11 genes were isolated in the European sea bass (Dicentrarchus. labrax), and named slc11a2-α and slc11a2-β, since both were found to be evolutionary closer to tetrapods SLC11A2, through phylogenetic analysis and comparative genomics. Induction of slc11a2-α and slc11a2-β in sea bass, upon iron modulation or exposure to Photobacterium damselae spp. piscicida, was evaluated in in vivo or in vitro experimental models. Overall, slc11a2-α was found to respond only to iron deficiency in the intestine, whereas slc11a2-β was found to respond to iron overload and bacterial infection in several tissues and also in the leukocytes.ConclusionsOur data suggests that despite the absence of slc11a1, its functions have been undertaken by one of the slc11a2 duplicated paralogs in teleost fish in a case of synfunctionalization, being involved in both iron metabolism and response to bacterial infection. This study provides, to our knowledge, the first example of this type of sub-functionalization in iron metabolism genes, illustrating how conserving the various functions of the SLC11 gene family is of crucial evolutionary importance.

Highlights

The SLC11A1/Nramp1 and SLC11A2/Nramp2 genes belong to the solute carrier family 11 (SLC11)/Nramp family of transmembrane divalent metal transporters, with SLC11A1 being associated with resistance to pathogens and SLC11A2 involved in intestinal iron uptake and transferrin-bound iron transport
Southern Blot In order to determine the number of copies of slc11 genes in the sea bass genome, a southern blot analysis was performed (Figure 1)
Sea bass slc11 transcripts Five different sea bass slc11 transcripts were obtained by primer walking and 5’/3’ RACE with liver, spleen and intestine cDNA and analysis of whole-genome shotgun contigs (Max Planck Institute for Molecular Genetics)

Summary

Introduction

The SLC11A1/Nramp and SLC11A2/Nramp genes belong to the SLC11/Nramp family of transmembrane divalent metal transporters, with SLC11A1 being associated with resistance to pathogens and SLC11A2 involved in intestinal iron uptake and transferrin-bound iron transport. Both members of the SLC11 gene family have been clearly identified in tetrapods; SLC11A1 has never been documented in teleost fish and is believed to have been lost in this lineage during early vertebrate evolution. The first member of the SLC11 family, SLC11A1, known as the natural resistance-associated macrophage protein 1 (NRAMP1), is a divalent cation/proton transporter, which has been proposed to function as either a symporter [1,2] or an antiporter [3,4]. Polymorphisms in SLC11A2 are known to underline microcytic anemia in mice and rats, resulting from an impairment of iron recycling and intestinal absorption [27,28]

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