Skip to main content
SpringerLink
Log in

The Mammalian 2′-5′ Oligoadenylate Synthetase Gene Family: Evidence for Concerted Evolution of Paralogous Oas1 Genes in Rodentia and Artiodactyla

  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

Multiple 2′-5′ oligoadenylate (2-5A) synthetases are important components of innate immunity in mammals. Gene families encoding these proteins have previously been studied mainly in humans and mice. To reconstruct the evolution of this gene family in mammals, a search for additional 2-5A synthetase genes was performed in rat, cattle, pig, and dog. Twelve 2′-5′ oligoadenylate synthetase (Oas) genes were identified in the rat genome, including eight Oas1 genes, two Oas1 pseudogenes, single copies of Oas2 and Oas3, and two Oas-like genes, Oasl1 and Oasl2. Four OAS genes were detected in the pig genome and five OAS genes were found in both the cattle and dog genomes. An OAS3 gene was not found in either the cattle or the pig genome. While two tandemly duplicated OAS-like (OASL) genes were identified in the dog genome, only a single OASL orthologue was found in both the cattle and the pig genomes. The bovine and porcine OASL genes contain premature stop codons and encode truncated proteins, which lack the typical C-terminal double ubiquitin domains. The cDNA sequences of the rat, cattle, pig, and dog OAS genes were amplified, sequenced and compared with each other and with those in the human, mouse, horse, and chicken genomes. Evidence of concerted evolution of paralogous 2′-5′ oligoadenylate synthetase 1 genes was obtained in rodents (Rodentia) and even-toed ungulates (Artiodactyla). Calculations using the nonparametric Kolmogorov-Smirnov test suggested that the homogenization of paralogous OAS1 sequences was due to gene conversion rather than stabilizing selection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402

    Article  PubMed  CAS  Google Scholar 

  • Annilo T, Chen ZQ, Shulenin S, Dean M (2003) Evolutionary analysis of a cluster of ATP-binding cassette (ABC) genes. Mammal Genome 14:7–20

    Article  PubMed  CAS  Google Scholar 

  • Archibald JM, Roger AJ (2002a) Gene conversion and the evolution of euryarchaeal chaperonins: a maximum likelihood-based method for detecting conflicting phylogenetic signals. J Mol Evol 55:232–245

    Article  CAS  Google Scholar 

  • Archibald JM, Roger AJ (2002b) Gene duplication and gene conversion shape the evolution of archaeal chaperonins. J Mol Biol 316:1041–1050

    Article  CAS  Google Scholar 

  • Benech P, Mory Y, Revel M, Chebath J (1985) Structure of two forms of the interferon-induced (2′-5′) oligo A synthetase of human cells based on cDNAs and gene sequences. EMBO J 4:2249–2256

    PubMed  CAS  Google Scholar 

  • Bettencourt BR, Feder ME (2002) Rapid concerted evolution via gene conversion at the Drosophila hsp70 genes. J Mol Evol 54:569–586

    Article  PubMed  CAS  Google Scholar 

  • Brinton MA, Perelygin AA (2003) Genetic resistance to flaviviruses. Adv Virus Res 60:43–85

    PubMed  CAS  Google Scholar 

  • Chebath J, Benech P, Hovanessian A, Galabru J, Revel M (1987a) Four different forms of interferon-induced 2′,5′-oligo(A) synthetase identified by immunoblotting in human cells. J Biol Chem 262:3852–3857

    CAS  Google Scholar 

  • Chebath J, Benech P, Revel M, Vigneron M (1987b) Constitutive expression of (2′-5′) oligo A synthetase confers resistance to picornavirus infection. Nature 330:587–588

    Article  CAS  Google Scholar 

  • Clemens MJ, Williams BR (1978) Inhibition of cell-free protein synthesis by pppA2′p5′A2′p5′A: a novel oligonucleotide synthesized by interferon-treated L cell extracts. Cell 13:565–572

    Article  PubMed  CAS  Google Scholar 

  • Desjardins PR, Burkman JM, Shrager JB, Allmond LA, Stedman HH (2002) Evolutionary implications of three novel members of the human sarcomeric myosin heavy chain gene family. Mol Biol Evol 19:375–393

    PubMed  CAS  Google Scholar 

  • Drouin G (2002a) Characterization of the gene conversions between the multigene family members of the yeast genome. J Mol Evol 55:14–23

    Article  CAS  Google Scholar 

  • Drouin G (2002b) Testing claims of gene conversion between multigene family members: examples from echinoderm actin genes. J Mol Evol 54:138–139

    Article  CAS  Google Scholar 

  • Eskildsen S, Hartmann R, Kjeldgaard NO, Justesen J (2002) Gene structure of the murine 2′-5′-oligoadenylate synthetase family. Cell Mol Life Sci 59:1212–1222

    Article  PubMed  CAS  Google Scholar 

  • Eskildsen S, Justesen J, Schierup MH, Hartmann R (2003) Characterization of the 2′-5′-oligoadenylate synthetase ubiquitin-like family. Nucleic Acids Res 31:3166–3173

    Article  PubMed  CAS  Google Scholar 

  • Ghosh A, Sarkar SN, Guo W, Bandyopadhyay S, Sen GC (1997) Enzymatic activity of 2′-5′-oligoadenylate synthetase is impaired by specific mutations that affect oligomerization of the protein. J Biol Chem 272:33220–33226

    Article  PubMed  CAS  Google Scholar 

  • Hartmann R, Olsen HS, Widder S, Jorgensen R, Justesen J (1998) p59OASL, a 2′-5′ oligoadenylate synthetase like protein: a novel human gene related to the 2′-5′ oligoadenylate synthetase family. Nucleic Acids Res 26:4121–4128

    Article  PubMed  CAS  Google Scholar 

  • Hartmann R, Justesen J, Sarkar SN, Sen GC, Yee VC (2003) Crystal structure of the 2′-specific and double-stranded RNA-activated interferon-induced antiviral protein 2′-5′-oligoadenylate synthetase. Mol Cell 12:1173–1185

    Article  PubMed  CAS  Google Scholar 

  • Higgs DR, Hill AV, Bowden DK, Weatherall DJ, Clegg JB (1984) Independent recombination events between the duplicated human alpha globin genes; implications for their concerted evolution. Nucleic Acids Res 12:6965–6977

    PubMed  CAS  Google Scholar 

  • Hovanessian AG, Brown RE, Kerr IM (1977) Synthesis of low molecular weight inhibitor of protein synthesis with enzyme from interferon-treated cells. Nature 268:537–540

    Article  PubMed  CAS  Google Scholar 

  • Hovnanian A, Rebouillat D, Mattei MG, Levy ER, Marie I, Monaco AP, Hovanessian AG (1998) The human 2′,5′-oligoadenylate synthetase locus is composed of three distinct genes clustered on chromosome 12q24.2 encoding the 100-, 69-, and 40-kDa forms. Genomics 52:267–277

    Article  PubMed  CAS  Google Scholar 

  • Ichii Y, Fukunaga R, Shiojiri S, Sokawa Y (1986) Mouse 2-5A synthetase cDNA: nucleotide sequence and comparison to human 2-5A synthetase. Nucleic Acids Res 14:10117

    PubMed  CAS  Google Scholar 

  • Israel RL, Kosakovsky Pond SL, Muse SV, Katz LA (2002) Evolution of duplicated alpha-tubulin genes in ciliates. Evol Int J Org Evol 56:1110–1122

    CAS  Google Scholar 

  • Iwata A, Yamamoto A, Fujino M, Sato I, Hosokawa-Kanai T, Tuchiya K, Ishihama A, Sokawa Y (2004) High level activity of 2′,5′-oligoadenylate synthetase in dog serum. J Vet Med Sci 66:721–724

    Article  PubMed  CAS  Google Scholar 

  • Jukes TH, Cantor CR (1969) Evolution of protein molecules. In: Munro NH (ed) Mammalian protein metabolism. Academic Press, New York, pp 21–123

    Google Scholar 

  • Jurka J, Kohany O, Pavlicek A, Kapitonov VV, Jurka MV (2004) Duplication, coclustering, and selection of human Alu retrotransposons. Proc Natl Acad Sci USA 101:1268–1272

    Article  PubMed  CAS  Google Scholar 

  • Justesen J, Hartmann R, Kjeldgaard NO (2000) Gene structure and function of the 2′-5′-oligoadenylate synthetase family. Cell Mol Life Sci 57:1593–1612

    Article  PubMed  CAS  Google Scholar 

  • Kakuta S, Shibata S, Iwakura Y (2002) Genomic structure of the mouse 2′,5′-oligoadenylate synthetase gene family. J Interferon Cytokine Res 22:981–993

    Article  PubMed  CAS  Google Scholar 

  • Khier H, Bartl S, Schuettengruber B, Seiser C (1999) Molecular cloning and characterization of the mouse histone deacetylase 1 gene: integration of a retrovirus in 129SV mice. Biochim Biophys Acta 1489:365–373

    PubMed  CAS  Google Scholar 

  • Kimura M (1980) A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol 16:111–120

    Article  PubMed  CAS  Google Scholar 

  • Kimura M (1981) Estimation of evolutionary differences between homologous nucleotide sequences. Proc Natl Acad Sci USA 78:454–458

    Article  PubMed  CAS  Google Scholar 

  • Kulski JK, Gaudieri S, Martin A, Dawkins RL (1999) Coevolution of PERB11 (MIC) and HLA class I genes with HERV-16 and retroelements by extended genomic duplication. J Mol Evol 49:84–97

    Article  PubMed  CAS  Google Scholar 

  • Kumar S, Mitnik C, Valente G, Floyd-Smith G (2000) Expansion and molecular evolution of the interferon-induced 2′-5′ oligoadenylate synthetase gene family. Mol Biol Evol 17:738–750

    PubMed  CAS  Google Scholar 

  • Larkin DM, Everts-van der Wind A, Rebeiz M, Schweitzer PA, Bachman S, Green C, Wright CL, Campos EJ, Benson LD, Edwards J, Liu L, Osoegawa K, Womack JE, de Jong PJ, Lewin HA (2003) A cattle-human comparative map built with cattle BAC-ends and human genome sequence. Genome Res 13:1966–1972

    PubMed  Google Scholar 

  • Lazzaro BP, Clark AG (2001) Evidence for recurrent paralogous gene conversion and exceptional allelic divergence in the Attacin genes of Drosophila melanogaster. Genetics 159:659–671

    PubMed  CAS  Google Scholar 

  • Li WH (1993) Unbiased estimation of the rates of synonymous and nonsynonymous substitution. J Mol Evol 36:96–99

    Article  PubMed  CAS  Google Scholar 

  • Marie I, Hovanessian AG (1992) The 69-kDa 2-5A synthetase is composed of two homologous and adjacent functional domains. J Biol Chem 267:9933–9999

    PubMed  CAS  Google Scholar 

  • Marie I, Svab J, Robert N, Galabru J, Hovanessian AG (1990) Differential expression and distinct structure of 69- and 100-kDa forms of 2-5A synthetase in human cells treated with interferon. J Biol Chem 265:18601–18607

    PubMed  CAS  Google Scholar 

  • Marie I, Blanco J, Rebouillat D, Hovanessian AG (1997) 69-kDa and 100-kDa isoforms of interferon-induced (2′-5′)oligoadenylate synthetase exhibit differential catalytic parameters. Eur J Biochem 248:558–566

    Article  PubMed  CAS  Google Scholar 

  • Mashimo T, Lucas M, Simon-Chazottes D, Frenkiel MP, Montagutelli X, Ceccaldi PE, Deubel V, Guenet JL, Despres P (2002) A nonsense mutation in the gene encoding 2′-5′-oligoadenylate synthetase/L1 isoform is associated with West Nile virus susceptibility in laboratory mice. Proc Natl Acad Sci USA 99:11311–11316

    Article  PubMed  CAS  Google Scholar 

  • Mashimo T, Glaser P, Lucas M, Simon-Chazottes D, Ceccaldi PE, Montagutelli X, Despres P, Guenet JL (2003) Structural and functional genomics and evolutionary relationships in the cluster of genes encoding murine 2′,5′-oligoadenylate synthetases. Genomics 82:537–552

    Article  PubMed  CAS  Google Scholar 

  • Nagawa F, Yoshihara S, Tsuboi A, Serizawa S, Itoh K, Sakano H (2002) Genomic analysis of the murine odorant receptor MOR28 cluster: a possible role of gene conversion in maintaining the olfactory map. Gene 292:73–80

    Article  PubMed  CAS  Google Scholar 

  • Needleman SB, Wunsch CD (1970) A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol 48:443–453

    Article  PubMed  CAS  Google Scholar 

  • Perelygin AA, Scherbik SV, Zhulin IB, Stockman BM, Li Y, Brinton MA (2002) Positional cloning of the murine flavivirus resistance gene. Proc Natl Acad Sci USA 99:9322–9327

    Article  PubMed  CAS  Google Scholar 

  • Perelygin AA, Lear TL, Zharkikh AA, Brinton MA (2005) Structure of equine 2′-5′ oligoadenylate synthetase (Oas) gene family and FISH mapping of Oas genes to ECA8p15-p14 and BTA17q24-25. Cytogenet Genome Res 111:51–56

    Article  PubMed  CAS  Google Scholar 

  • Rebouillat D, Marie I, Hovanessian AG (1998) Molecular cloning and characterization of two related and interferon-induced 56-kDa and 30-kDa proteins highly similar to 2′-5′ oligoadenylate synthetase. Eur J Biochem 257:319–330

    Article  PubMed  CAS  Google Scholar 

  • Rebouillat D, Hovnanian A, Marie I, Hovanessian AG (1999) The 100-kDa 2′,5′-oligoadenylate synthetase catalyzing preferentially the synthesis of dimeric pppA2′p5′A molecules is composed of three homologous domains. J Biol Chem 274:1557–1565

    Article  PubMed  CAS  Google Scholar 

  • Rogozin IB, Aravind L, Koonin EV (2003) Differential action of natural selection on the N and C-terminal domains of 2′-5′ oligoadenylate synthetases and the potential nuclease function of the C-terminal domain. J Mol Biol 326:1449–1461

    Article  PubMed  CAS  Google Scholar 

  • Rooney AP, Piontkivska H, Nei M (2002) Molecular evolution of the nontandemly repeated genes of the histone 3 multigene family. Mol Biol Evol 19:68–75

    PubMed  CAS  Google Scholar 

  • Rutherford MN, Kumar A, Nissim A, Chebath J, Williams BR (1991) The murine 2-5A synthetase locus: three distinct transcripts from two linked genes. Nucleic Acids Res 19:1917–1924

    PubMed  CAS  Google Scholar 

  • Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425

    PubMed  CAS  Google Scholar 

  • Shibata S, Kakuta S, Hamada K, Sokawa Y, Iwakura Y (2001) Cloning of a novel 2′,5′-oligoadenylate synthetase-like molecule, Oasl5 in mice. Gene 271:261–271

    Article  PubMed  CAS  Google Scholar 

  • Shimizu T, Kawakita S, Li QH, Fukuhara S, Fujisawa J (2003) Human T-cell leukemia virus type 1 Tax protein stimulates the interferon-responsive enhancer element via NF-kappaB activity. FEBS Lett 539:73–77

    Article  PubMed  CAS  Google Scholar 

  • Smith JB, Nguyen TT, Hughes HJ, Herschman HR, Widney DP, Bui KC, Rovai LE (2002) Glucocorticoid-attenuated response genes induced in the lung during endotoxemia. Am J Physiol Lung Cell Mol Physiol 283:L636–L647

    PubMed  CAS  Google Scholar 

  • Tatusova TA, Madden TL (1999) Blast 2 sequences—a new tool for comparing protein and nucleotide sequences. FEMS Microbiol Lett 174:247–250

    Article  PubMed  CAS  Google Scholar 

  • Tiefenthaler M, Marksteiner R, Neyer S, Koch F, Hofer S, Schuler G, Nussenzweig M, Schneider R, Heufler C (1999) M1204, a novel 2′,5′ oligoadenylate synthetase with a ubiquitin-like extension, is induced during maturation of murine dendritic cells. J Immunol 163:760–765

    PubMed  CAS  Google Scholar 

  • Truve E, Aaspollu A, Honkanen J, Puska R, Mehto M, Hassi A, Teeri TH, Kelve M, Seppanen P, Saarma M (1993) Transgenic potato plants expressing mammalian 2′-5′ oligoadenylate synthetase are protected from potato virus X infection under field conditions. Biotechnology (NY) 11:1048–1052

    Article  CAS  Google Scholar 

  • Witt PL, Marie I, Robert N, Irizarry A, Borden EC, Hovanessian AG (1993) Isoforms p69 and p100 of 2′,5′-oligoadenylate synthetase induced differentially by interferons in vivo and in vitro. J Interferon Res 13:17–23

    PubMed  CAS  Google Scholar 

  • Yang Z, Yu CY (2000) Organizations and gene duplications of the human and mouse MHC complement gene clusters. Exp Clin Immunogenet 17:1–17

    Article  PubMed  Google Scholar 

  • Zhao Z, Hewett-Emmett D, Li WH (1998) Frequent gene conversion between human red and green opsin genes. J Mol Evol 46:494–496

    Article  PubMed  CAS  Google Scholar 

  • Zharkikh A, Li WH (1995) Estimation of confidence in phylogeny: the complete-and-partial bootstrap technique. Mol Phylogenet Evol 4:44–63

    Article  PubMed  CAS  Google Scholar 

  • Zharkikh AA, Rzhetsky A, Morosov PS, Sitnikova TL, Krushkal JS (1991) VOSTORG: a package of microcomputer programs for sequence analysis and construction of phylogenetic trees. Gene 101:251–254

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Jonathan Beever for providing porcine cDNA and Ping Jiang for assistance in DNA sequencing. This work was supported by Public Health Service Research Grant AI045135 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health; by Grant CI000216 from the National Center for Infectious Diseases, Centers for Disease Control and Prevention; and by a grant from the Southeastern Center for Emerging Biologic Threats through Grant/Cooperative Agreement U38/CCU423095 from CDC. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of CDC or the Southeastern Center for Emerging Biologic Threats.

Author information

Authors and Affiliations

  1. Biology Department, Georgia State University, P.O. Box 4010, Atlanta, GA, 30302-4010, USA

    Andrey A. Perelygin, Svetlana V. Scherbik & Margo A. Brinton

  2. Bioinformatics Department, Myriad Genetics, Inc., Salt Lake City, UT, 84108, USA

    Andrey A. Zharkikh

Authors
  1. Andrey A. Perelygin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrey A. Zharkikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Svetlana V. Scherbik
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Margo A. Brinton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrey A. Perelygin.

Additional information

Reviewing Editor: Dr. Martin Kreitman

Electronic Supplementary Material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Perelygin, A.A., Zharkikh, A.A., Scherbik, S.V. et al. The Mammalian 2′-5′ Oligoadenylate Synthetase Gene Family: Evidence for Concerted Evolution of Paralogous Oas1 Genes in Rodentia and Artiodactyla. J Mol Evol 63, 562–576 (2006). https://doi.org/10.1007/s00239-006-0073-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00239-006-0073-3

Keywords

Search

Navigation