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Phylogenetic analyses uncover a novel clade of transferrin in nonmammalian vertebrates.
Mohd-Padil H
,
Mohd-Adnan A
,
Gabaldón T
.
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Transferrin is a protein super-family involved in iron transport, a central process in cellular homeostasis. Throughout the evolution of vertebrates, transferrin members have diversified into distinct subfamilies including serotransferrin, ovotransferrin, lactoferrin, melanotransferrin, the inhibitor of carbonic anhydrase, pacifastin, and the major yolk protein in sea urchin. Previous phylogenetic analyses have established the branching order of the diverse transferrin subfamilies but were mostly focused on the transferrin repertoire present in mammals. Here, we conduct a comprehensive phylogenetic analysis of transferrin protein sequences in sequenced vertebrates, placing a special focus on the less-studied nonmammalian vertebrates. Our analyses uncover a novel transferrin clade present across fish, sauropsid, and amphibian genomes but strikingly absent from mammals. Our reconstructed scenario implies that this novel class emerged through a duplication event at the vertebrate ancestor, and that it was subsequently lost in the lineage leading to mammals. We detect footprints of accelerated evolution following the duplication event, which suggest positive selection and early functional divergence of this novel clade. Interestingly, the loss of this novel class of transferrin in mammals coincided with the divergence by duplication of lactoferrin and serotransferrin in this lineage. Altogether, our results provide novel insights on the evolution of iron-binding proteins in the various vertebrate groups.
Fig. 1. Phylogenetic tree of vertebrate transferrins based on Bayesian and ML analyses. Major groups of vertebrate transferrins are resolved, including the newly identified clade (clade IV). Clade III is divided into several subfamilies, some of which emerged from more recent duplications. Numbers on the branches indicate Bayesian posterior probabilities followed by bootstrap support in the ML analyses. If the partition does not appear in the ML tree, this is indicated with an asterisk. The final log likelihood of the ML tree was −40,597.96204 and the gamma shape parameter 1.336.
Fig. 2. Topology for a subset of transferrin proteins used for the branch-specific model. Branches subtending the newly identified group and serotransferrins were assumed to have different rate from a background. The branch of novel transferrin indicates ω > 0 shows that the genes have undergone position selection. # indicates the branches that have different rate of substitution (dN/dS = ω).
Fig. 3. Type 2 functional divergence. (a) Thirteen amino acids residues with posterior ratio more than 8 have been observed from type 2 functional divergence. The observation of amino acids location that have high posterior ratio (R > 8) shows that each cluster has a conserved radical change between each other. (b) The 3D protein for transferrin protein in Lates calcarifer was modeled to show the location of residues affected by radical changes. Five of the residues that have high posterior ratio found to form loop, five forming α-helix, whereas another three forming the β-strand. Tyr524 is the functional residue for iron binding, which has been substituted to Asp in novel sequences. Arg121 and Arg460 involve in anion binding, which has been substituted to Trp and Ser in the novel sequences, respectively. The substitutions of important residues might suggest that those sites may responsible to perform a different function after the duplication event. The locations of the residues are calculated based on the Gallus gallus ovotransferrin sequence (2D3I) obtained from PDB database (last accessed November 1, 2012).
Aisen,
Lactoferrin and transferrin: a comparative study.
1972, Pubmed
Aisen,
Lactoferrin and transferrin: a comparative study.
1972,
Pubmed
Andersen,
Polymorphism, selection and tandem duplication of transferrin genes in Atlantic cod (Gadus morhua)--conserved synteny between fish monolobal and tetrapod bilobal transferrin loci.
2011,
Pubmed
Anderson,
Structure of human lactoferrin at 3.2-A resolution.
1987,
Pubmed
Aoki,
Identification of viral induced genes in Ig+ leucocytes of Japanese flounder Paralichthys olivaceus, by differential hybridisation with subtracted and un-subtracted cDNA probes.
2000,
Pubmed
Bateman,
The Pfam protein families database.
2004,
Pubmed
Beard,
Iron biology in immune function, muscle metabolism and neuronal functioning.
2001,
Pubmed
Bernstein,
The Protein Data Bank: a computer-based archival file for macromolecular structures.
1977,
Pubmed
Bjellqvist,
Reference points for comparisons of two-dimensional maps of proteins from different human cell types defined in a pH scale where isoelectric points correlate with polypeptide compositions.
1994,
Pubmed
Blom,
Sequence and structure-based prediction of eukaryotic protein phosphorylation sites.
1999,
Pubmed
Caipang,
Intraperitoneal vaccination of Atlantic cod, Gadus morhua with heat-killed Listonella anguillarum enhances serum antibacterial activity and expression of immune response genes.
2008,
Pubmed
Capella-Gutiérrez,
trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses.
2009,
Pubmed
Cheng,
Structure of the human transferrin receptor-transferrin complex.
2004,
Pubmed
Ciuraszkiewicz,
Reptilian transferrins: evolution of disulphide bridges and conservation of iron-binding center.
2007,
Pubmed
Cunningham,
Structural organization of the mouse lactoferrin gene.
1992,
Pubmed
Darriba,
ProtTest 3: fast selection of best-fit models of protein evolution.
2011,
Pubmed
Dehal,
Two rounds of whole genome duplication in the ancestral vertebrate.
2005,
Pubmed
Do,
ProbCons: Probabilistic consistency-based multiple sequence alignment.
2005,
Pubmed
Douglas,
Comprehensive EST analysis of Atlantic halibut (Hippoglossus hippoglossus), a commercially relevant aquaculture species.
2007,
Pubmed
Edgar,
MUSCLE: multiple sequence alignment with high accuracy and high throughput.
2004,
Pubmed
Ellis,
Innate host defense mechanisms of fish against viruses and bacteria.
2001,
Pubmed
Farnaud,
Lactoferrin--a multifunctional protein with antimicrobial properties.
2003,
Pubmed
Finn,
HMMER web server: interactive sequence similarity searching.
2011,
Pubmed
Flicek,
Ensembl 2012.
2012,
Pubmed
Ford,
Molecular evolution of transferrin: evidence for positive selection in salmonids.
2001,
Pubmed
Ford,
Natural selection promotes divergence of transferrin among salmonid species.
1999,
Pubmed
Gabaldón,
Large-scale assignment of orthology: back to phylogenetics?
2008,
Pubmed
Gomme,
Transferrin: structure, function and potential therapeutic actions.
2005,
Pubmed
Graham,
A comparsion of glycopeptides from the transferrins of several species.
1975,
Pubmed
Greene,
Physical evidence for transferrins as single polypeptide chains.
1968,
Pubmed
Gu,
Statistical methods for testing functional divergence after gene duplication.
1999,
Pubmed
Gu,
DIVERGE: phylogeny-based analysis for functional-structural divergence of a protein family.
2002,
Pubmed
Gu,
Maximum-likelihood approach for gene family evolution under functional divergence.
2001,
Pubmed
Guindon,
New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0.
2010,
Pubmed
He,
Inequivalence of the two tyrosine ligands in the N-lobe of human serum transferrin.
1997,
Pubmed
Katoh,
Recent developments in the MAFFT multiple sequence alignment program.
2008,
Pubmed
Lambert,
Evolution of the transferrin family: conservation of residues associated with iron and anion binding.
2005,
Pubmed
,
Echinobase
Lambert,
Evolution of duplications in the transferrin family of proteins.
2005,
Pubmed
,
Echinobase
Lambert,
Molecular evolution of the transferrin family and associated receptors.
2012,
Pubmed
Larkin,
Clustal W and Clustal X version 2.0.
2007,
Pubmed
Lassmann,
Kalign2: high-performance multiple alignment of protein and nucleotide sequences allowing external features.
2009,
Pubmed
Lee,
Multiple sequence alignment using partial order graphs.
2002,
Pubmed
Liang,
Positive selection drives lactoferrin evolution in mammals.
2010,
Pubmed
Liu,
Structure and expression of transferrin gene of channel catfish, Ictalurus punctatus.
2010,
Pubmed
Löytynoja,
Phylogeny-aware gap placement prevents errors in sequence alignment and evolutionary analysis.
2008,
Pubmed
MacGillivray,
Two high-resolution crystal structures of the recombinant N-lobe of human transferrin reveal a structural change implicated in iron release.
1998,
Pubmed
Mikawa,
Structure of medaka transferrin gene and its 5'-flanking region.
1996,
Pubmed
Mizutani,
Structure of aluminium-bound ovotransferrin at 2.15 Angstroms resolution.
2005,
Pubmed
Moretti,
The M-Coffee web server: a meta-method for computing multiple sequence alignments by combining alternative alignment methods.
2007,
Pubmed
Murayama,
Otolith matrix proteins OMP-1 and Otolin-1 are necessary for normal otolith growth and their correct anchoring onto the sensory maculae.
2005,
Pubmed
Nakamasu,
Membrane-bound transferrin-like protein (MTf): structure, evolution and selective expression during chondrogenic differentiation of mouse embryonic cells.
1999,
Pubmed
Nei,
Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions.
1986,
Pubmed
Notredame,
T-Coffee: A novel method for fast and accurate multiple sequence alignment.
2000,
Pubmed
Octave,
Iron mobilization from cultured hepatocytes: effect of desferrioxamine B.
1983,
Pubmed
Ong,
Increased uptake of divalent metals lead and cadmium into the brain after kainite-induced neuronal injury.
2006,
Pubmed
Pakdaman,
Transferrins--a mechanism for iron uptake by lactoferrin.
1998,
Pubmed
Palaksha,
Evaluation of non-specific immune components from the skin mucus of olive flounder (Paralichthys olivaceus).
2008,
Pubmed
Peatman,
Microarray analysis of gene expression in the blue catfish liver reveals early activation of the MHC class I pathway after infection with Edwardsiella ictaluri.
2008,
Pubmed
Pei,
PCMA: fast and accurate multiple sequence alignment based on profile consistency.
2003,
Pubmed
Pettersen,
UCSF Chimera--a visualization system for exploratory research and analysis.
2004,
Pubmed
Phuong,
Multiple alignment of protein sequences with repeats and rearrangements.
2006,
Pubmed
Rombel,
ORF-FINDER: a vector for high-throughput gene identification.
2002,
Pubmed
Ronquist,
MrBayes 3: Bayesian phylogenetic inference under mixed models.
2003,
Pubmed
Saleh,
Myelination and motor coordination are increased in transferrin transgenic mice.
2003,
Pubmed
Sarropoulou,
Profiling of infection specific mRNA transcripts of the European seabass Dicentrarchus labrax.
2009,
Pubmed
Schaeffer,
Complete structure of the human transferrin gene. Comparison with analogous chicken gene and human pseudogene.
1987,
Pubmed
Schultz,
SMART, a simple modular architecture research tool: identification of signaling domains.
1998,
Pubmed
Sekyere,
The membrane-bound transferrin homologue melanotransferrin: roles other than iron transport?
2000,
Pubmed
Sigrist,
PROSITE, a protein domain database for functional characterization and annotation.
2010,
Pubmed
Stafford,
Products of proteolytic cleavage of transferrin induce nitric oxide response of goldfish macrophages.
2001,
Pubmed
Subramanian,
DIALIGN-TX: greedy and progressive approaches for segment-based multiple sequence alignment.
2008,
Pubmed
Tamura,
MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0.
2007,
Pubmed
Tan,
Identification and analysis of a prepro-chicken gonadotropin releasing hormone II (preprocGnRH-II) precursor in the Asian seabass, Lates calcarifer, based on an EST-based assessment of its brain transcriptome.
2008,
Pubmed
Teehan,
Iron storage indices: novel predictors of bacteremia in hemodialysis patients initiating intravenous iron therapy.
2004,
Pubmed
Tsantes,
Age at first reproduction explains rate variation in the strepsirrhine molecular clock.
2009,
Pubmed
UniProt Consortium,
Reorganizing the protein space at the Universal Protein Resource (UniProt).
2012,
Pubmed
Wang,
Assembly of 500,000 inter-specific catfish expressed sequence tags and large scale gene-associated marker development for whole genome association studies.
2010,
Pubmed
Williams,
A comparison of glycopeptides from the ovotransferrin and serum transferrin of the hen.
1968,
Pubmed
Yang,
Positive selection on multiple antique allelic lineages of transferrin in the polyploid Carassius auratus.
2004,
Pubmed
Yang,
PAML 4: phylogenetic analysis by maximum likelihood.
2007,
Pubmed