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Evidence for positive Darwinian selection on the hepcidin gene of Perciform and Pleuronectiform fishes

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Abstract

Hepcidin is a small cysteine-rich peptide that plays an important role in antimicrobial activity and in maintaining iron homeostasis in vertebrates. Here we report on the underlying mechanism that maintains high sequence diversities among the hepcidin-like variants of perciform and pleuronectiform fishes. In contrast to mammals, maximum likelihood-based codon substitution analyses revealed that positive Darwinian selection (nonsynonymous to synonymous substitution, ω  > 1) is the likely cause of accelerated rate of amino acid substitutions in the hepcidin mature peptide region of these fishes. Comparison of models incorporating positive selection (ω  >  1) at certain sites with models not incorporating positive selection (ω <  1) failed to reject (p  =  0) the evidence of positive selection among the codon sites of percifom and pleuronectiform hepcidin. The adaptive evolution of this peptide in perciform and pleuronectiform fishes might be directed by pathogens when the host is exposed to new habitats/environments.

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Abbreviations

AMP:

Antimicrobial peptide

ML:

Maximum likelihood

BI:

Bayesian inference

NJ:

Neighbour joining

JTT:

Jones-Taylor-Thornton

dN :

Nonsynonymous nucleotide substitutions per nonsynonymous site

dS :

Synonymous substitutions per synonymous site

ω :

dN/dS

HKY:

Hasegawa-Kishino-Yano

AIC:

Akaike Information Criterion

hLR:

Hierarchical likelihood ratio test

Γ:

Invariable sites

γ :

Gamma distribution shape parameter

References

  • Chen S, Li W, Meng L, Sha Z, Wang Z and Ren G (2007). Molecular cloning and expression analysis of a hepcidin antimicrobial peptide gene from turbot (Scophthalmus maximus). Fish Shellfish Immunol 22: 172–181

    Article  CAS  Google Scholar 

  • Douglas S, Gallant J, Liebscher R, Dacanay A and Tsoi S (2003). Identification and expression analysis of hepcidin-like antimicrobial peptides in bony fish. Dev Comp Immunol 27: 589–601

    Article  CAS  Google Scholar 

  • Lauth X, Babon J, Stannard J, Singh S, Nizet V, Carlberg J, Ostland Ve, Penningnton MW, Norton RS and Westerman SE (2005). Bass hepcidin synthesis, solution structure, antimicrobial activities and synergism, and in vivo hepatic response to bacterial infections. J Biol Chem 280: 9272–9282

    Article  CAS  Google Scholar 

  • Lehrer RI and Ganz T (1999). Antimicrobial peptides in mammalian and insect host defence. Curr Opin Immunol 11: 23–27

    Article  CAS  Google Scholar 

  • Rodrigues P, Vazquez-Dorado S, Neves J and Wilson J (2006). Dual function of fish hepcidin: response to experimental iron overload and bacterial infection in sea bass (Dicentrarchus labrax). Dev Comp Immunol 30: 1156–1167

    Article  CAS  Google Scholar 

  • Shike H, Shimizu C, Lauth X and Burns JC (2004). Organization and expression analysis of the zebrafish hepcidin gene, an antimicrobial peptide gene conserved among vertebrates. Dev Comp Immunol 28: 747–754

    Article  CAS  Google Scholar 

  • Bowman HG (2003). Antibacterial peptides: basic facts and emerging concepts. J Intern Med 254: 197–215

    Article  Google Scholar 

  • Hedengren M, Borge K and Hultmark D (2000). Expression and evolution of the Drosophila Attacin/Diptericin gene family. Biochem Biophys Res Comm 279: 574–581

    Article  CAS  Google Scholar 

  • Tennessen JA (2005). Molecular evolution of animal antimicrobial peptides: widespread moderate positive selection. J Evol Biol 18: 1387–1394

    Article  CAS  Google Scholar 

  • Nicolas P, Vanhoye D and Amiche M (2003). Molecular strategies in biological evolution of antibacterial peptides. Peptides 24: 1669–1680

    Article  CAS  Google Scholar 

  • Padhi A, Verghese B, Otta S, Varghese B and Ramu K (2007). Adaptive evolution after duplication of penaeidin antimicrobial peptides. Fish Shellfish Immunol 23: 553–566

    Article  CAS  Google Scholar 

  • Kimura M (1983). The neutral theory of molecular evolution. Cambridge University press, New York

    Google Scholar 

  • Bulmer M and Crozier R (2004). Duplication and diversifying selection among termite antifungal peptides. Mol Biol Evol 21: 2256–2564

    Article  CAS  Google Scholar 

  • Duda TJ, Vanhoye D and Nicolas P (2002). Roles of diversifying selection and coordinated evolution in the evolution of Amphibian antimicrobial peptides. Mol Biol Evol 19: 858–864

    CAS  Google Scholar 

  • Hughes A and Yeager M (1997). Coordinated amino acid changes in the evolution of mammalian defensins. J Mol Evol 44: 675–685

    Article  CAS  Google Scholar 

  • Semple C, Rolfe M and Dorin J (2003). Duplication and selection in the evolution of primate β-defensin genes. Genome Biol 4: R31

    Article  Google Scholar 

  • Shi J and Camus A (2006). Hepcidins in amphibians and fishes: Antimicrobial peptides or iron-regulatory hormones?. Dev Comp Immunol 30: 746–755

    Article  CAS  Google Scholar 

  • Shike H, Lauth X, Westerman ME, Ostland VE, Carlberg JM, Olst JCV, Shimizu C, Bulet P and Burns JC (2002). Bass hepcidin is a novel antimicrobial peptide induced by bacterial challenge. Eur J Biochem 269: 2232–2237

    Article  CAS  Google Scholar 

  • Brogden KA (2005). Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?. Nat Rev Microbiol 3: 238–250

    Article  CAS  Google Scholar 

  • Hunter HN, Fultons DB, Ganz T and Vogel HJ (2002). The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis. J Biol Chem 277: 37597–37603

    Article  CAS  Google Scholar 

  • Hirono I, Hwang J, Ono Y, Kurobe T, Ohira T, Nozaki R and Takashi A (2005). Two different types of hepcidins from the Japanese flounder Paralichthys olivaceus. FEBS J 272: 5257–5264

    Article  CAS  Google Scholar 

  • Chen S, Xu M, Ji X, Yu G and Liu Y (2005). Cloning, characterization, and expression analysis of hepcidin gene from red sea bream (Chrysophrys major). Antimicrob Agents Chemother 49: 1608–1612

    Article  CAS  Google Scholar 

  • Kim Y, Hong S, Nam B, Lee J, Kim K and Lee S (2005). Molecular cloning and expression analysis of two hepcidin genes from olive flounder Paralichthys olivaceus. Biosci Biotechnol Biochem 69: 1411–1414

    Article  CAS  Google Scholar 

  • Ren H, Wang K, Zhou H and Yang M (2006). Cloning and organisation analysis of a hepcidin-like gene and cDNA from Japan sea bass, Lateolabrax japonicus. Fish Shellfish Immunol 3: 221–227

    Article  CAS  Google Scholar 

  • Ford M (2002). Applications of selective neutrality tests to molecular ecology. Mol Ecol 11: 1245–1262

    Article  CAS  Google Scholar 

  • Hughes AL and Nei M (1989). Nucleotide substitution at major histocompatibility complex class II loci: evidence for overdominant selection. Proc Natl Acad Sci USA 86: 958–962

    Article  CAS  Google Scholar 

  • Yang Z, Nielsen R, Goldman N and Pederson A (2000). Codon-substitution models for heterogeneous selection pressures at amino acid sites. Genetics 155: 431–449

    CAS  Google Scholar 

  • Xia X (2000). Data analysis in molecular biology and evolution. Kluwer Academic Publishers, Boston

    Google Scholar 

  • Xia X and Xie Z (2001). DAMBE: Data analysis in molecular biology and evolution. J Heredity 92: 371–373

    Article  CAS  Google Scholar 

  • Hall T (1999). BioEdit: a user friendly biological sequence alignment editor and analyses program for windows 95/98/N.T. Nucl Acids Symp Ser 41: 95–98

    CAS  Google Scholar 

  • Maddison Y, Maddison D, Mesquite: A modular system for evolutionary analysis. Version 1.12. http://mesquiteproject.org. 2006

  • Guindon S and Gascuel O (2003). A simple, fast and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52: 696–704

    Article  Google Scholar 

  • Huelsenbeck J and Ronquist F (2001). MRBAYES: Bayesian inference of phylogenetic trees. Bioinformatics 17: 754–755

    Article  CAS  Google Scholar 

  • Kumar S, Tamura K and Nei M (2004). MEGA3.1: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment. Briefings in Bioinformatics 5: 150–163

    Article  CAS  Google Scholar 

  • Rambout A, Drummond A, Tracer. Version 1.3 Available from http://evolve.zoo.ox.ac.uk/. In, 2003

  • Yang Z (1997). PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci 13: 555–556

    CAS  Google Scholar 

  • Posada D and Crandall K (1998). Modeltest: testing the model of DNA substitution. Bioinformatics 14: 817–818

    Article  CAS  Google Scholar 

  • Swofford DL, PAUP*. Phylogenetic analysis using parsimony (and other methods) ver. 4.0.10b. Sunderland: Sinauer Associates, 2002

  • Rozas J, Sánchez-DelBarrio JC, Messeguer X and Rozas R (2003). DnaSP, DNA polymorphism analyses by the coalescent and other methods. Bioinformatics 19: 2496–2497

    Article  CAS  Google Scholar 

  • Morrison G, Semple C, Kilanowski F, Hill R and Dorin J (2003). Signal sequence conservation and mature peptide divergence within subgroups of the murine β-defensin gene family. Mol Biol Evol 20: 460–470

    Article  CAS  Google Scholar 

  • Yang Z (1998). Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Mol Biol Evol 15: 568–573

    CAS  Google Scholar 

  • Swanson W, Nielsen R and Yang Q (2003). Pervasive adaptive evolution in mammalian fertilization proteins. Mol Biol Evol 20: 18–20

    CAS  Google Scholar 

  • Yang Z, Wong W and Nielsen R (2005). Bayes empirical Bayes inference of amino acid sites under positive selection. Mol Biol Evol 22: 1107–1118

    Article  CAS  Google Scholar 

  • Maddison WP (1997). Gene trees in species trees. Syst Biol 46: 523–536

    Article  Google Scholar 

  • Tennessen JA (2005). Enhanced synonymous site divergence in positively selected vertebrate antimicrobial peptide genes. J Mol Evol 61: 445–455

    Article  CAS  Google Scholar 

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  1. Abinash Padhi

    Present address: Department of Biology, Mueller Lab, The Pennsylvania State University, University Park, PA, 16802, USA

Authors and Affiliations

  1. Department of Biological Science, University of Tulsa, 600 S. College Ave., Tulsa, OK, 74104, USA

    Abinash Padhi & Bindhu Verghese

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  1. Abinash Padhi
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  2. Bindhu Verghese
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Correspondence to Abinash Padhi.

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Padhi, A., Verghese, B. Evidence for positive Darwinian selection on the hepcidin gene of Perciform and Pleuronectiform fishes. Mol Divers 11, 119–130 (2007). https://doi.org/10.1007/s11030-007-9066-4

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  • DOI: https://doi.org/10.1007/s11030-007-9066-4

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