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Isolation, Characterization, and Evolutionary Divergence of Mouse RNase 6: Evidence for Unusual Evolution in Rodents

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Abstract

The evolution of the ribonuclease A (RNase A) vertebrate-specific enzyme family is interesting in that specific gene lineages appear to be responding to unique selective pressures in wildly diverse manners to generate proteins that are capable of reducing the infectivity of viruses, killing systemic pathogens, and inducing the growth of blood vessels all while maintaining the signature motifs of a ribonuclease. In this paper, we present the DNA sequence and gene structure of Mus musculus RNase 6 and examine the expression pattern and enzymatic activity of the recombinant protein. M. musculus RNase 6 has a limited expression pattern compared to human RNase 6 and is an efficient ribonuclease, with a catalytic efficiency 17-fold higher than that of human protein. Evo- lutionary analysis reveals that RNase 6 was subject to unusual evolutionary forces (dN/dS = 1.2) in an ancestral rodent lineage before the separation of Mus and Rattus. However, more recent evolution of rodent RNase 6 has been relatively conserved, with an average dN/dS of 0.66. These data suggest that the ancestral rodent RNase 6 was subject to accelerated evolution, resulting in the conserved modern gene, which most likely plays an important role in mouse physiology.

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References

  • D Batten KD Dyer JB Domachowske HF Rosenberg (1997) ArticleTitleMolecular cloning of four novel murine ribonuclease genes: Unusual expansion within the ribonuclease A gene family Nucleic Acids Res 25 4235–4239

    Google Scholar 

  • JJ Beintema C Schuller M Irie A Carsana (1988) ArticleTitleMolecular evolution of the ribonuclease superfamily Prog Biophys Mol Biol 51 165–192

    Google Scholar 

  • JJ Beintema HJ Breukelman JY Dubois HW Warmels (2003) ArticleTitlePhylogeny of ruminants secretory ribonuclease gene sequences of pronghom (Antilocapra americana) Mol Phylogenet Evol 26 18–25

    Google Scholar 

  • SA Cormier KA Larson S Yuan TL Mitchell K Lindenberger P Carrigan NA Lee JJ Lee (2001) ArticleTitleMouse eosinophil-associated ribonucleases: A unique subfamily expressed during hematopoiesis Mamm Genome 12 352–361

    Google Scholar 

  • MS Deming KD Dyer AT Bankier MB Piper PH Dear HF Rosenberg (1998) ArticleTitleRibonuclease k6: Chromosomal mapping and divergent rates of evolution within the RNase A gene superfamily Genome Res 8 599–607

    Google Scholar 

  • JB Domachowske CA Bonville KD Dyer HF Rosenberg (1998a) ArticleTitleEvolution of antiviral activity in the ribonuclease A gene superfamily: Evidence for a specific interaction between eosinophil-derived neurotoxm (EDN/RNase 2) and respiratory syncytial virus Nucleic Acids Res 26 5327–5332

    Google Scholar 

  • JB Domachowske KD Dyer AG Adams TL Leto HF Rosenberg (1998b) ArticleTitleEosinophil cationic protein/RNase 3 is another RNase A-family ribonuclease with direct antiviral activity Nucleic Acids Res 26 3358–3363

    Google Scholar 

  • JY Dubois BM Ursing JA Kolkman JJ Beintema (2003) ArticleTitleMolecular evolution of mammalian ribonucleases 1 Mol Phylogenet Evol 27 453–463

    Google Scholar 

  • KD Dyer T Nitto JM Moreau AL McDevitt HF Rosenberg (2004) ArticleTitleIdentification of a purine-rich intronic enhancer element in the mouse eosinophil-associated ribnuclease 2 (mEar 2) gene Mamm Genome 15 1–9

    Google Scholar 

  • J Felsenstein (1985) ArticleTitleConfidence limits on phylogenies: An approach using the bootstrap Evolution 39 783–791

    Google Scholar 

  • J Futami Y Tsushima Y Murato H Tada J Sasaki M Seno H Yamada (1997) ArticleTitleTissue-specific expression of pancreatic-type RNases and RNase inhibitor in humans DNA Cell Biol 16 413–419

    Google Scholar 

  • JS Handen HF Rosenberg (1997) ArticleTitleIntronic enhancer activity of the eosinophil-derived neurotoxin (RNS2) and eosinophil cationic protein (RNS3) genes is mediated by an NFAT-1 consensus binding sequence J Biol Chem 272 1665–1669

    Google Scholar 

  • LV Hooper TS Stappenbeck CV Hong JI Gordon (2003) ArticleTitleAngiogenins: A new class of microbicidal proteins involved in innate immunity Nat Immunol 4 269–273

    Google Scholar 

  • M Kimura (1980) ArticleTitleA simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences J Mol Evol 16 111–120 Occurrence Handle1:CAS:528:DyaL3MXmtFSktg%3D%3D Occurrence Handle7463489

    CAS  PubMed  Google Scholar 

  • S Kumar K Tamura IB Jakobsen M Nei (2001) ArticleTitleMEGA2: Molecular evolutionary genetics analysis software Bioinformatics 17 1244–1245 Occurrence Handle10.1093/bioinformatics/17.12.1244 Occurrence Handle1:CAS:528:DC%2BD38XmtVCktQ%3D%3D Occurrence Handle11751241

    Article  CAS  PubMed  Google Scholar 

  • ES Lander LM Linton B Birren et al. (2001) ArticleTitleInitial sequencing and analysis of the human genome Nature 409 860–921 Occurrence Handle10.1038/35057062 Occurrence Handle11237011

    Article  PubMed  Google Scholar 

  • KA Larson EV Olson BJ Madden GJ Gleich NA Lee JJ Lee (1996) ArticleTitleTwo highly homologous ribonuclease genes expressed in mouse eosinophils identify a larger subgroup of the mammalian ribonuclease superfamily Proc Natl Acad Sci USA 93 12370–12375

    Google Scholar 

  • AL McDevitt MS Deming HF Rosenberg KD Dyer (2001) ArticleTitleGene structure and enzymatic activity of mouse eosinophil-associated ribonuclease 2 Gene 267 23–30

    Google Scholar 

  • PM Murphy (1993) ArticleTitleMolecular mimicry and the generation of host defense protein diversity Cell 72 823–826

    Google Scholar 

  • WJ Murphy E Eizirik SJ O’Brien O Madsen M Scally CJ Douady E Teeling OA Ryder MJ Stanhope WW Jong Particlede MS Springer (2001) ArticleTitleResolution of the early placental mammal radiation using Bayesian phylogenetics Science 294 2348–2351 Occurrence Handle10.1126/science.1067179 Occurrence Handle1:CAS:528:DC%2BD3MXptFGrtrg%3D Occurrence Handle11743200

    Article  CAS  PubMed  Google Scholar 

  • D Pietrowski M Forster (2000) ArticleTitleComplete cDNA sequence and amino acid analysis of a bovine ribonuclease K6 gene DNA Seq 11 365–371

    Google Scholar 

  • HF Rosenberg JB Domachowske (2001) ArticleTitleEosinophils, eosinophil ribonucleases, and their role in host defense against respiratory virus pathogens J Leukoc Biol 70 691–698 Occurrence Handle1:CAS:528:DC%2BD3MXosVKlsLw%3D Occurrence Handle11698487

    CAS  PubMed  Google Scholar 

  • HF Rosenberg KD Dyer (1995) ArticleTitleHuman ribonuclease 4 (RNase 4) Coding sequence, chromosomal localization and identification of two distinct transcripts in human somatic tissues Nucleic Acids Res 23 4290–4295

    Google Scholar 

  • HF Rosenberg KD Dyer (1996) ArticleTitleMolecular cloning and characterization of a novel human ribonuclease (RNase k6): Increasing diversity in the enlarging ribonuclease gene family Nucleic Acids Res 24 3507–3513

    Google Scholar 

  • HF Rosenberg KD Dyer HL Tiffany M Gonzalez (1995) ArticleTitleRapid evolution of a unique family of primate ribonuclease genes Nat Genet 10 219–232

    Google Scholar 

  • N Saitou M Nei (1987) ArticleTitleThe neighbor-joining method: A new method for reconstructing phylogenetic trees Mol Biol Evol 4 406–425 Occurrence Handle1:STN:280:BieC1cbgtVY%3D Occurrence Handle3447015

    CAS  PubMed  Google Scholar 

  • MP Sasso M Lombardi E Confalone A Carsana M Palmieri A Furia (1999) ArticleTitleThe differential pattern of tissue-specific expression of ruminant pancreatic type ribonucleases may help to understand the evolutionary history of their genes Gene 227 205–212

    Google Scholar 

  • NA Singhania KD Dyer J Zhang MS Deming CA Bonville JB Domachowske HP Rosenberg (1999) ArticleTitleRapid evolution of the ribonuclease A superfamily: Adaptive expansion of independent gene clusters in rats and mice J Mol Evol 49 721–728

    Google Scholar 

  • NR Slifman DA Loegering DJ McKean GJ Gleich (1986) ArticleTitleRibonuclease activity associated with human eosinophil-derived neurotoxin and eosinophil cationic protein J Immunol 137 2913–2917

    Google Scholar 

  • DJ Strydom (1998) ArticleTitleThe angiogenins Cell Mol Life Sci 54 811–824

    Google Scholar 

  • F Tajima (1993) ArticleTitleSimple methods for testing the molecular evolutionary clock hypothesis Genetics 135 599–607 Occurrence Handle1:CAS:528:DyaK2cXlt1yhtbw%3D Occurrence Handle8244016

    CAS  PubMed  Google Scholar 

  • JW Thomas JW Touchman RW Blakesley et al. (2003) ArticleTitleComparative analyses of multi-species sequences from targeted genomic regions Nature 424 788–793 Occurrence Handle10.1038/nature01858 Occurrence Handle1:CAS:528:DC%2BD3sXmt1antrs%3D Occurrence Handle12917688

    Article  CAS  PubMed  Google Scholar 

  • JD Thompson TJ Gibson F Plewniak F Jeanmougin DG Higgins (1997) ArticleTitleThe CLUSTAL_X windows interface: Flexible strategies for multiple sequence alignment aided by quality analysis tools Nucleic Acids Res 25 4876–4882 Occurrence Handle10.1093/nar/25.24.4876 Occurrence Handle1:CAS:528:DyaK1cXntFyntQ%3D%3D Occurrence Handle9396791

    Article  CAS  PubMed  Google Scholar 

  • HL Tiffany JS Handen HF Rosenberg (1996) ArticleTitleEnhanced expression of the eosinophil-derived neurotoxin ribonuclease (RNS2) gene requires interaction between the promoter and intron J Biol Chem 271 12387–12393

    Google Scholar 

  • J Zhang S Kumar M Nei (1997) ArticleTitleSmall-sample tests of episodic adaptive evolution: A case study of primate lysozymes Mol Biol Evol 14 1335–1338

    Google Scholar 

  • J Zhang HF Rosenberg M Nei (1998) ArticleTitlePositive Darwinian selection after gene duplication in primate ribonuclease genes Proc Natl Acad Sci USA 95 3708–3713 Occurrence Handle10.1073/pnas.95.7.3708 Occurrence Handle1:CAS:528:DyaK1cXitlKjtrc%3D Occurrence Handle9520431

    Article  CAS  PubMed  Google Scholar 

  • J Zhang KD Dyer HF Rosenberg (2000) ArticleTitleEvolution of the rodent eosinophil-associated RNase gene family by rapid gene sorting and positive selection Proc Natl Acad Sci USA 97 4701–4706

    Google Scholar 

  • J Zhang KD Dyer HF Rosenberg (2002a) ArticleTitleRNase 8, a novel RNase A superfamily ribonuclease expressed uniquely in placenta Nucleic Acids Res 30 1169–1175

    Google Scholar 

  • J Zhang YP Zhang HF Rosenberg (2002b) ArticleTitleAdaptive evolution of a duplicated pancreatic ribonuclease gene in a leaf-eating monkey Nat Genet 30 411–415

    Google Scholar 

  • J Zhang KD Dyer HF Rosenberg (2003) ArticleTitleHuman RNase 7: A new cationic ribonuclease of the RNase A superfamily Nucleic Acids Res 31 602–607

    Google Scholar 

Download references

Acknowledgment

Dr. Jianzhi Zhang is support by NIH Grant GM67030.

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Correspondence to Kimberly D. Dyer.

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Reviewing Editor: Dr. Lauren Ancel Meyers

The GenBank accession numbers for the new genes presented here are as follows: Mus musculus, AY545655; Rattus norvegicus, AY545654; Mus spicilegus, AY545653; Mus caroli, AY545651; and Mus pahari, AY545652.

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Dyer, K.D., Rosenberg, H.F. & Zhang, J. Isolation, Characterization, and Evolutionary Divergence of Mouse RNase 6: Evidence for Unusual Evolution in Rodents. J Mol Evol 59, 657–665 (2004). https://doi.org/10.1007/s00239-004-2657-0

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  • DOI: https://doi.org/10.1007/s00239-004-2657-0

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