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Pathogen-driven Adaptive Evolution of Myxovirus Resistance (Mx) Genes in Fishes

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Abstract

Myxovirus resistance (Mx) proteins, which belong to the dynamin super-family, are known to inhibit RNA viral replication in a wide range of taxonomic groups, including fishes. Given their crucial role in host immune defense, the key amino acid residues in the GTP effector domain (GED) near the C-terminus are expected to evolve adaptively in order to protect the host against invading viral pathogens. The present study reveals the role of recombination and positive selection in the evolution of Mx proteins in fishes. While the GTP-binding domain in the N-terminal domain has experienced purifying selection, several amino acid residues in GED have evolved under positive selection, thus indicating adaptive evolution. Given the antiviral activity of GED, the adaptive evolutionary changes that were observed in this region are therefore predicted to be pathogen-driven.

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References

  • Abollo E, Ordas C, Dios S, Figueras A, Novoa B (2005) Molecular characterisation of a turbot Mx cDNA. Fish Shellfish Immunol 19:185–190

    Article  PubMed  CAS  Google Scholar 

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    PubMed  CAS  Google Scholar 

  • Berlin S, Qu L, Li X, Yang N, Ellegren H (2008) Positive diversifying selection in avian Mx genes. Immunogenetics 60:689–697

    Article  PubMed  CAS  Google Scholar 

  • Boni MF, Posada D, Feldman MW (2007) An exact nonparametric method for inferring mosaic structure in sequence triplets. Genetics 176:1035–1047

    Article  PubMed  CAS  Google Scholar 

  • Caipang CM, Hirono I, Aoki T (2003) In vitro inhibition of fish rhabdoviruses by Japanese flounder, Paralichthys olivaceus Mx. Virology 317:373–382

    Article  PubMed  CAS  Google Scholar 

  • Chen YM, Su YL, Lin JH, Yang HL, Chen TY (2006) Cloning of an orange-spotted grouper (Epinephelus coioides) Mx cDNA and characterisation of its expression in response to nodavirus. Fish Shellfish Immunol 20:58–71

    Article  PubMed  CAS  Google Scholar 

  • Chen YM, Su YL, Shie PS, Huang SL, Yang HL, Chen TY (2008) Grouper Mx confers resistance to nodavirus and interacts with coat protein. Dev Comp Immunol 32:825–836

    Article  PubMed  CAS  Google Scholar 

  • Dettai A, Lecointre G (2005) Further support for the clades obtained by multiple molecular phylogenies in the acanthomorph bush. CR Biol 328:674–689

    Article  CAS  Google Scholar 

  • Fernández-Trujillo MA, Garcia-Rosado E, Alonso MC, Borrego JJ, Alvarez MC, Bejar J (2011a) Differential antiviral activity of Mx1, Mx2 and Mx3 proteins from gilthead seabream (Sparus aurata) against infectious pancreatic necrosis virus (IPNV). Mol Immunol 49:107–114

    Article  PubMed  Google Scholar 

  • Fernández-Trujillo MA, Novel P, Manchado M, Sepulcre MP, Mulero V, Borrego JJ, Alvarez MC, Béjar J (2011b) Three Mx genes with differential response to VNNV infection have been identified in gilthead seabream (Sparus aurata). Mol Immunol 48:1216–1223

    Article  PubMed  Google Scholar 

  • Gibbs MJ, Armstrong JS, Gibbs AJ (2000) Sister-scanning: a Monte Carlo procedure for assessing signals in recombinant sequences. Bioinformatics 16:573–582

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • He G, He B, Racey PA, Cui J (2010) Positive selection of the bat interferon alpha gene family. Biochem Genet 48:840–846

    Article  PubMed  CAS  Google Scholar 

  • Hou ZC, Xu GY, Su Z, Yang N (2007) Purifying selection and positive selection on the myxovirus resistance gene in mammals and chickens. Gene 396:188–195

    Article  PubMed  CAS  Google Scholar 

  • Hughes AL, 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  PubMed  CAS  Google Scholar 

  • Jensen I, Albuquerque A, Sommer AI, Robertsen B (2002) Effect of poly I:C on the expression of Mx proteins and resistance against infection by infectious salmon anaemia virus in Atlantic salmon. Fish Shellfish Immunol 13:311–326

    Article  PubMed  CAS  Google Scholar 

  • Jensen V, Robertsen B (2000) Cloning of an Mx cDNA from Atlantic halibut (Hippoglossus hippoglossus) and characterization of Mx mRNA expression in response to double-stranded RNA or infectious pancreatic necrosis virus. J Interferon Cytokine Res 20:701–710

    Article  PubMed  CAS  Google Scholar 

  • Kerns JA, Emerman M, Malik HS (2008) Positive selection and increased antiviral activity associated with the PARP-containing isoform of human zinc-finger antiviral protein. PLoS Genet 4:e21

    Article  PubMed  Google Scholar 

  • Lee JY, Hirono I, Aoki T (2000) Cloning and analysis of expression of Mx cDNA in Japanese flounder, Paralichthys olivaceus. Dev Comp Immunol 24:407–415

    Article  PubMed  CAS  Google Scholar 

  • Lee SH, Vidal SM (2002) Functional diversity of Mx proteins: variations on a theme of host resistance to infection. Genome Res 12:527–530

    Article  PubMed  CAS  Google Scholar 

  • Li G, Zhang J, Sun Y, Wang H, Wang Y (2009) The evolutionarily dynamic IFN-inducible GTPase proteins play conserved immune functions in vertebrates and cephalochordates. Mol Biol Evol 26:1619–1630

    Article  PubMed  CAS  Google Scholar 

  • Lin CH, Christopher John JA, Lin CH, Chang CY (2006) Inhibition of nervous necrosis virus propagation by fish Mx proteins. Biochem Biophys Res Commun 351:534–539

    Article  PubMed  CAS  Google Scholar 

  • Martin D, Rybicki E (2000) RDP: detection of recombination amongst aligned sequences. Bioinformatics 16:562–563

    Article  PubMed  CAS  Google Scholar 

  • Martin DP, Williamson C, Posada D (2005) RDP2: recombination detection and analysis from sequence alignments. Bioinformatics 21:260–262

    Article  PubMed  CAS  Google Scholar 

  • Martin DP, Lemey P, Lott M, Moulton V, Posada D, Lefeuvre P (2010) RDP3: a flexible and fast computer program for analyzing recombination. Bioinformatics 26:2462–2463

    Article  PubMed  CAS  Google Scholar 

  • Meier E, Kunz G, Haller O, Arnheiter H (1990) Activity of rat Mx proteins against a rhabdovirus. J Virol 64:6263–6269

    PubMed  CAS  Google Scholar 

  • Melen K, Ronni T, Broni B, Krug RM, von Bonsdorff CH, Julkunen I (1992) Interferon-induced Mx proteins form oligomers and contain a putative leucine zipper. J Biol Chem 267:25898–25907

    PubMed  CAS  Google Scholar 

  • Padhi A (2012) Adaptive evolution of crustin antimicrobial peptides in decapods. Genetica 140:197–203

    Article  PubMed  Google Scholar 

  • Padhi A (2013) Positive selection drives rapid evolution of certain amino acid residues in an evolutionarily highly conserved interferon-inducible antiviral protein of fishes. Immunogenetics 65(1):75–81

    Article  PubMed  CAS  Google Scholar 

  • Padhi A, Verghese B (2007) Evidence for positive Darwinian selection on the hepcidin gene of Perciform and Pleuronectiform fishes. Mol Divers 11:119–130

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Padidam M, Sawyer S, Fauquet CM (1999) Possible emergence of new geminiviruses by frequent recombination. Virology 265:218–225

    Article  PubMed  CAS  Google Scholar 

  • Patel MR, Loo YM, Horner SM, Gale M Jr, Malik HS (2012) Convergent evolution of escape from hepaciviral antagonism in primates. PLoS Biol 10:e1001282

    Article  PubMed  CAS  Google Scholar 

  • Pavlovic J, Staeheli P (1991) The antiviral potentials of Mx proteins. J Interferon Res 11:215–219

    Article  PubMed  CAS  Google Scholar 

  • Pavlovic J, Haller O, Staeheli P (1992) Human and mouse Mx proteins inhibit different steps of the influenza virus multiplication cycle. J Virol 66:2564–2569

    PubMed  CAS  Google Scholar 

  • Pavlovic J, Arzet HA, Hefti HP, Frese M, Rost D, Ernst B, Kolb E, Staeheli P, Haller O (1995) Enhanced virus resistance of transgenic mice expressing the human MxA protein. J Virol 69:4506–4510

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Posada D, Crandall KA (2001) Evaluation of methods for detecting recombination from DNA sequences: computer simulations. Proc Natl Acad Sci USA 98:13757–13762

    Article  PubMed  CAS  Google Scholar 

  • Sadler AJ, Williams BR (2008) Interferon-inducible antiviral effectors. Nat Rev Immunol 8:559–568

    Article  PubMed  CAS  Google Scholar 

  • Saint-Jean SR, Perez-Prieto SI (2007) Effects of salmonid fish viruses on Mx gene expression and resistance to single or dual viral infections. Fish Shellfish Immunol 23:390–400

    Article  PubMed  CAS  Google Scholar 

  • Sawyer SL, Emerman M, Malik HS (2007) Discordant evolution of the adjacent antiretroviral genes TRIM22 and TRIM5 in mammals. PLoS Pathog 3:e197

    Article  PubMed  Google Scholar 

  • Smith JM (1992) Analyzing the mosaic structure of genes. J Mol Evol 34:126–129

    PubMed  CAS  Google Scholar 

  • Stertz S, Dittmann J, Blanco JC, Pletneva LM, Haller O, Kochs G (2007) The antiviral potential of interferon-induced cotton rat Mx proteins against orthomyxovirus (influenza) rhabdovirus and bunyavirus. J Interferon Cytokine Res 27:847–855

    Article  PubMed  CAS  Google Scholar 

  • Tafalla C, Aranguren R, Secombes CJ, Figueras A, Novoa B (2004) Cloning and analysis of expression of a gilthead sea bream (Sparus aurata) Mx cDNA. Fish Shellfish Immunol 16:11–24

    Article  PubMed  CAS  Google Scholar 

  • Tamura K, Dudley J, Nei M, Kumar S (2007) Mega4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599

    Article  PubMed  CAS  Google Scholar 

  • Workenhe ST, Rise ML, Kibenge MJ, Kibenge FS (2010) The fight between the teleost fish immune response and aquatic viruses. Mol Immunol 47:2525–2536

    Article  PubMed  CAS  Google Scholar 

  • Wu YC, Chi SC (2006) Persistence of betanodavirus in Barramundi brain (BB) cell line involves the induction of interferon response. Fish Shellfish Immunol 21:540–547

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Zhu YF, Li HF, Han W, Shu JT, Song WT, Zhang XY, Chen KW (2010) Detecting adaptive evolution of galliform and anseriform avian Mx genes. J Animal Vet Adv 9:1811–1815

    Article  CAS  Google Scholar 

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Correspondence to Abinash Padhi.

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Padhi, A. Pathogen-driven Adaptive Evolution of Myxovirus Resistance (Mx) Genes in Fishes. Biochem Genet 51, 626–634 (2013). https://doi.org/10.1007/s10528-013-9592-y

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