Skip to main content
SpringerLink
Log in

Serpins in Unicellular Eukarya, Archaea, and Bacteria: Sequence Analysis and Evolution

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

Abstract

Most serpins irreversibly inactivate specific serine proteinases of the chymotrypsin family. Inhibitory serpins are unusual proteins in that their native structure is metastable, and rapid conversion to a relaxed state is required to trap target enzymes in a covalent complex. The evolutionary origin of the serpin fold is unresolved, and while serpins in animals are known to be involved in the regulation of a remarkable diversity of metabolic processes, the physiological functions of homologues from other phyla are unknown. Addressing these questions, here we analyze serpin genes identified in unicellular eukaryotes: the green alga Chlamydomonas reinhardtii, the dinoflagellate Alexandrium tamarense, and the human pathogens Entamoeba spp., Eimera tenella, Toxoplasma gondii, and Giardia lamblia. We compare these sequences to others, particularly those in the complete genome sequences of Archaea, where serpins were found in only 4 of 13 genera, and Bacteria, in only 9 of 56 genera. The serpins from unicellular organisms appear to be phylogenetically distinct from all of the clades of higher eukaryotic serpins. Most of the sequences from unicellular organisms have the characteristics of inhibitory serpins, and where multiple serpin genes are found in one genome, variability is displayed in the region of the reactive-center loop important for specificity. All the unicellular eukaryotic serpins have large hydrophobic or positively charged residues at the putative P1 position. In contrast, none of the prokaryotic serpins has a residue of these types at the predicted P1 position, but many have smaller, neutral residues. Serpin evolution is discussed.

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

Similar content being viewed by others

References

  • SF Altschul TL Madden AA Schäffer J Zhang Z Zhang W Miller DJ Lipman (1997) ArticleTitleGapped BLAST and PSI-BLAST: A new generation of protein database search programs Nucleic Acids Res 25 3389–3402 Occurrence Handle1:CAS:528:DyaK2sXlvFyhu7w%3D Occurrence Handle9254694

    CAS  PubMed  Google Scholar 

  • WR Atchley T Lokot K Wollenberg A Dress H Ragg (2001) ArticleTitlePhylogenetic analyses of amino acid variation in the serpin proteins Mol Biol Evol 18 1502–1511 Occurrence Handle1:CAS:528:DC%2BD3MXlslOis70%3D Occurrence Handle11470841

    CAS  PubMed  Google Scholar 

  • Q Bao Y Tian W Li Z Xu Z Xuan S Hu W Dong J Yang Y Chen Y Xue Y Xu X Lai L Huang X Dong Y Ma L Ling H Tan R Chen J Wang H Yu J Yang (2002) ArticleTitleA complete sequence of the T. tengcongensis genome Genome Res 12 689–700 Occurrence Handle10.1101/gr.219302 Occurrence Handle1:CAS:528:DC%2BD38XjvFSgt7g%3D Occurrence Handle11997336

    Article  CAS  PubMed  Google Scholar 

  • KW Barbour RL Goodwin F Guillonneau Y Wang H Baumann FG Berger (2002) ArticleTitleFunctional diversification during evolution of the murine alpha(1)-proteinase inhibitor family: Role of the hypervariable reactive center loop Mol Biol Evol 19 718–727 Occurrence Handle1:CAS:528:DC%2BD38XjsFaku70%3D Occurrence Handle11961105

    CAS  PubMed  Google Scholar 

  • A Bollen A Herzog A Cravador P Herion P Chuchana A Vander-Straten R Loriau P Jacobs A Elsen Particlevan (1983) ArticleTitleCloning and expression in Escherichia coli of full-length complementary DNA coding for human alpha 1-antitrypsin DNA 2 255–264 Occurrence Handle1:CAS:528:DyaL2cXpslGqsQ%3D%3D Occurrence Handle6319097

    CAS  PubMed  Google Scholar 

  • MF Bonaldo G Lennon MB Soares (1996) ArticleTitleNormalization and subtraction: Two approaches to facilitate gene discovery Genome Res 6 791–806 Occurrence Handle1:CAS:528:DyaK28XlvF2ns7Y%3D Occurrence Handle8889548

    CAS  PubMed  Google Scholar 

  • DR Boone GM Castenholz GM Garrity (Eds) (2001) Bergey’s manual of systematic bacteriology (2nd ed.), Vol 1 Springer New York

    Google Scholar 

  • RW Carrell J Travis (1985) ArticleTitleAlpha-1-antitrypsin and the serpins: variation and countervariation Trends Biochem Sci 10 20–24 Occurrence Handle10.1016/0968-0004(85)90011-8 Occurrence Handle1:CAS:528:DyaL2MXhvVWitbg%3D

    Article  CAS  Google Scholar 

  • JR Dahlen DC Foster W Kisiel (1997) ArticleTitleHuman proteinase inhibitor 9 (PI9) is a potent inhibitor of subtilisin Biochem Biophys Res Commun 238 329–333 Occurrence Handle10.1006/bbrc.1997.7282 Occurrence Handle1:CAS:528:DyaK2sXmsVGks7Y%3D Occurrence Handle9299506

    Article  CAS  PubMed  Google Scholar 

  • WL DeLano (2002) The PyMOL molecular graphics system DeLano Scientific San Carlos, CA

    Google Scholar 

  • U Deppenmeier A Johann T Hartsch R Merkl RA Schmitz R Martinez-Arias A Henne A Wiezer S Baeumer C Jacobi H Brueggemann T Lienard A Christmann M Boemecke S Steckel A Bhattacharyya A Lykidis R Overbeek H-P Klenk RP Gunsalus H-J Fritz G Gottschalk (2002) ArticleTitleThe genome of Methanosarcina mazei: Evidence for lateral gene transfer between Bacteria and Archaea J Mol Microbiol Biotechnol 4 453–461 Occurrence Handle1:CAS:528:DC%2BD38XlsVGks7Y%3D Occurrence Handle12125824

    CAS  PubMed  Google Scholar 

  • PR Elliott JP Abrahams DA Lomas (1998) ArticleTitleWild-type alpha 1-antitrypsin is in the canonical inhibitory conformation J Mol Biol 275 419–425 Occurrence Handle10.1006/jmbi.1997.1458 Occurrence Handle1:CAS:528:DyaK1cXpsVegtQ%3D%3D Occurrence Handle9466920

    Article  CAS  PubMed  Google Scholar 

  • MA Faust RA Gulledge (2002) ArticleTitleIdentifying harmful marine dinoflagellates Contrib US Nat Herb 42 1–144

    Google Scholar 

  • ST Fitz-Gibbon H Ladner UJ Kim KO Stetter MI Simon JH Miller (2002) ArticleTitleGenome sequence of the hyperthermophilic crenarchaeon Pyrobaculum aerophilum Proc Natl Acad Sci USA 99 984–989 Occurrence Handle10.1073/pnas.241636498 Occurrence Handle1:CAS:528:DC%2BD38Xht1Witr8%3D Occurrence Handle11792869

    Article  CAS  PubMed  Google Scholar 

  • PGW Gettins (2002) ArticleTitleSerpin structure, mechanism and function Chem Rev 102 4751–4803 Occurrence Handle10.1021/cr010170+ Occurrence Handle1:CAS:528:DC%2BD38XosFSgu7Y%3D Occurrence Handle12475206

    Article  CAS  PubMed  Google Scholar 

  • EH Harris (1989) The Chlamydomonas sourcebook: A comprehensive guide to biology and laboratory use Academic Press London

    Google Scholar 

  • SJ Harrop L Jankova M Coles D Jardine JS Whittaker AR Gould A Meister GC King BC Mabbutt PM Curmi (1999) ArticleTitleThe crystal structure of plasminogen activator inhibitor 2 at 2.0 A resolution: implications for serpin function Struct Fold Des 7 43–54 Occurrence Handle10.1016/S0969-2126(99)80008-2 Occurrence Handle1:CAS:528:DyaK1MXhtFGqtrg%3D

    Article  CAS  Google Scholar 

  • J Hejgaard S Hauge (2002) ArticleTitleSerpins of oat (Avena sativa) grain with distinct reactive centres and inhibitory specificity Physiol Plant 116 155–163 Occurrence Handle10.1034/j.1399-3054.2002.1160204.x Occurrence Handle1:CAS:528:DC%2BD38XnslSktLY%3D Occurrence Handle12354191

    Article  CAS  PubMed  Google Scholar 

  • RE Hill ND Hastie (1987) ArticleTitleAccelerated evolution in the reactive centre regions of serine protease inhibitors Nature 326 96–99 Occurrence Handle10.1038/326096a0 Occurrence Handle1:CAS:528:DyaL2sXktVWktb8%3D Occurrence Handle3493437

    Article  CAS  PubMed  Google Scholar 

  • PC Hopkins RW Carrell SR Stone (1993) ArticleTitleEffects of mutations in the hinge region of serpins Biochemistry 32 7650–7657 Occurrence Handle1:CAS:528:DyaK3sXkvV2ktb4%3D Occurrence Handle8347575

    CAS  PubMed  Google Scholar 

  • R Huber RW Carrell (1989) ArticleTitleImplications of the three-dimensional structure of alpha 1-antitrypsin for structure and function of serpins Biochemistry 28 8951–8966 Occurrence Handle1:CAS:528:DyaL1MXmtFSku7Y%3D Occurrence Handle2690952

    CAS  PubMed  Google Scholar 

  • JA Huntington RJ Read RW Carrell (2000) ArticleTitleStructure of a serpin-protease complex shows inhibition by deformation Nature 407 923–926 Occurrence Handle10.1038/35038119 Occurrence Handle1:CAS:528:DC%2BD3cXns1OksLw%3D Occurrence Handle11057674

    Article  CAS  PubMed  Google Scholar 

  • JA Irving RN Pike AM Lesk JC Whisstock (2000) ArticleTitlePhylogeny of the serpin superfamily: Implications of patterns of amino acid conservation for structure and function Genome Res 10 1845–1864 Occurrence Handle10.1101/gr.GR-1478R Occurrence Handle1:CAS:528:DC%2BD3MXhtVY%3D Occurrence Handle11116082

    Article  CAS  PubMed  Google Scholar 

  • JA Irving PJM Steenbakkers AM Lesk HJM Op den Camp RN Pike JC Whisstock (2002) ArticleTitleSerpins in prokaryotes Mol Biol Evol 19 1881–1890 Occurrence Handle1:CAS:528:DC%2BD38XovFOntLc%3D Occurrence Handle12411597

    CAS  PubMed  Google Scholar 

  • JA Irving LD Cabrita J Rossjohn RN Pike SP Bottomley JC Whisstock (2003) ArticleTitleThe 1.5Å crystal structure of a prokaryote serpin: Controlling conformational change in a heated environment Structure 11 387–397 Occurrence Handle10.1016/S0969-2126(03)00057-1 Occurrence Handle1:CAS:528:DC%2BD3sXislelurg%3D Occurrence Handle12679017

    Article  CAS  PubMed  Google Scholar 

  • H Jiang Y Wang Y Huang AB Mulnix J Kadel K Cole MR Kanost (1996) ArticleTitleOrganization of serpin gene-1 from Mandura sexta J Biol Chem 271 28017–28023 Occurrence Handle10.1074/jbc.271.45.28017 Occurrence Handle1:CAS:528:DyaK28XmvVWlsbw%3D Occurrence Handle8910411

    Article  CAS  PubMed  Google Scholar 

  • T Kaneko Y Nakamura CP Wolk T Kuritz S Sasamoto A Watanabe M Iriguchi A Ishikawa K Kawashima T Kimura Y Kishida M Kohara M Matsumoto A Matsuno A Muraki N Nakazaki S Shimpo M Sugimoto M Takazawa M Yamada M Yasuda S Tabata (2001) ArticleTitleComplete genomic sequence of the filamentous nitrogen-fixing cyanobacterium Anabaena sp. strain PCC 7120 DNA Res 8 205–213 Occurrence Handle1:CAS:528:DC%2BD3MXotlCgu7k%3D Occurrence Handle11759840

    CAS  PubMed  Google Scholar 

  • SE Keates TA Kostman JD Anderson BA Bailey (2003) ArticleTitleAltered gene expression in three plant species in response to treatment with Nep1, a fungal protein that causes necrosis Plant Physiol 132 1610–1622 Occurrence Handle10.1104/pp.102.019836 Occurrence Handle1:CAS:528:DC%2BD3sXlsFGhu7g%3D Occurrence Handle12857840

    Article  CAS  PubMed  Google Scholar 

  • MM Krem E Di Cera (2003) ArticleTitleConserved Ser residues, the shutter region, and speciation in serpin evolution J Biol Chem 278 37810–37814 Occurrence Handle10.1074/jbc.M305088200 Occurrence Handle1:CAS:528:DC%2BD3sXnsV2lt7Y%3D Occurrence Handle12847097

    Article  CAS  PubMed  Google Scholar 

  • O Kruger J Ladewig K Koster H Ragg (2002) ArticleTitleWidespread occurrence of serpin genes with multiple reactive centre-containing exon cassettes in insects and nematodes Gene 293 97–105 Occurrence Handle10.1016/S0378-1119(02)00697-2 Occurrence Handle1:CAS:528:DC%2BD38XlsFyksLw%3D Occurrence Handle12137947

    Article  CAS  PubMed  Google Scholar 

  • H Loebermann R Tokuoka J Deisenhofer R Huber (1984) ArticleTitleHuman alpha 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function J Mol Biol 177 531–557 Occurrence Handle10.1016/0022-2836(84)90298-5 Occurrence Handle1:CAS:528:DyaL2cXls1Kitb8%3D Occurrence Handle6332197

    Article  CAS  PubMed  Google Scholar 

  • DA Lomas DL Evans C Upton G McFadden RW Carrell (1993) ArticleTitleInhibition of plasmin, urokinase, tissue plasminogen activator, and CIS by a myxoma virus serine proteinase inhibitor J Biol Chem 268 516–521 Occurrence Handle1:CAS:528:DyaK3sXhtF2mtLc%3D Occurrence Handle8416956

    CAS  PubMed  Google Scholar 

  • J Lu Y Nogi H Takami (2001) ArticleTitleOceanobacillus iheyensis gen. nov., sp. nov., a deep-sea extremely halotolerant and alkaliphilic species isolated from a depth of 1050 m on the Iheya Ridge FEMS Microbiol Lett 205 291–297 Occurrence Handle10.1016/S0378-1097(01)00493-1 Occurrence Handle1:CAS:528:DC%2BD3MXpt1als7Y%3D Occurrence Handle11750818

    Article  CAS  PubMed  Google Scholar 

  • H Østergaard SK Rasmussen TH Roberts J Hejgaard (2000) ArticleTitleInhibitory serpins from wheat grain with reactive centers resembling glutamine-rich repeats of prolamin storage proteins. Cloning and characterization of five major molecular forms J Biol Chem 275 33272–33279 Occurrence Handle10.1074/jbc.M004633200 Occurrence Handle10874043

    Article  PubMed  Google Scholar 

  • CA Ray RA Black SR Kronheim TA Greenstreet PR Sleath GS Salvesen DJ Pickup (1992) ArticleTitleViral inhibition of inflammation: Cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme Cell 69 597–604 Occurrence Handle10.1016/0092-8674(92)90223-Y Occurrence Handle1:CAS:528:DyaK38Xks1yiu7Y%3D Occurrence Handle1339309

    Article  CAS  PubMed  Google Scholar 

  • M Renatus Q Zhou HR Stennicke SJ Snipas D Turk LA Bankston RC Liddington GS Salvesen (2000) ArticleTitleCrystal structure of the apoptotic suppressor CrmA in its cleaved form Struct Fold Des 8 789–797 Occurrence Handle10.1016/S0969-2126(00)00165-9 Occurrence Handle1:CAS:528:DC%2BD3cXltVKjtr4%3D

    Article  CAS  Google Scholar 

  • Y Riahi R Siman-Tov S Ankri (2004) ArticleTitleMolecular cloning, expression and characterization of a serine protease inhibitor gene from Entamoeba histolytica Mol Biochem Parasitol 133 153–162 Occurrence Handle10.1016/j.molbiopara.2003.10.003 Occurrence Handle1:CAS:528:DC%2BD3sXpvF2ku70%3D Occurrence Handle14698428

    Article  CAS  PubMed  Google Scholar 

  • TH Roberts S Marttila SK Rasmussen J Hejgaard (2003) ArticleTitleDifferential gene expression for suicide-substrate serine proteinase inhibitors (serpins) in vegetative and grain tissues of barley J Exp Bot 54 2251–2263 Occurrence Handle10.1093/jxb/erg248 Occurrence Handle1:CAS:528:DC%2BD3sXns1CnsLk%3D Occurrence Handle14504298

    Article  CAS  PubMed  Google Scholar 

  • I Rosenkrands J Hejgaard SK Rasmussen SE Bjorn (1994) ArticleTitleSerpins from wheat grain FEBS Lett 343 75–80 Occurrence Handle10.1016/0014-5793(94)80610-1 Occurrence Handle1:CAS:528:DyaK2cXktVektbo%3D Occurrence Handle8163022

    Article  CAS  PubMed  Google Scholar 

  • K Rutherford J Parkhill J Crook T Horsnell P Rice M-A Rajandream B Barrell (2000) ArticleTitleArtemis: sequence visualisation and annotation Bioinformatics 16 944–945 Occurrence Handle10.1093/bioinformatics/16.10.944 Occurrence Handle1:CAS:528:DC%2BD3MXjvVWksw%3D%3D Occurrence Handle11120685

    Article  CAS  PubMed  Google Scholar 

  • DN Saunders L Jankova SJ Harrop PM Curmi AR Gould M Ranson MS Baker (2001) ArticleTitleInteraction between the P14 residue and strand 2 of beta-sheet B is critical for reactive center loop insertion in plasminogen activator inhibitor-2 J Biol Chem 276 43383–43389 Occurrence Handle10.1074/jbc.M103123200 Occurrence Handle1:CAS:528:DC%2BD3MXptleltbs%3D Occurrence Handle11555638

    Article  CAS  PubMed  Google Scholar 

  • NFW Saunders T Thomas PMG Curmi JS Mattick E Kuczek R Slade J Davis PD Franzmann D Boone K Rusterholtz R Feldman C Gates S Bench K Sowers K Kadner A Aerts P Dehal C Detter T Glavina S Lucas P Richardson F Larimer L Hauser M Land R Cavicchioli (2003) ArticleTitleMechanisms of thermal adaptation revealed from the genomes of the Antarctic Archaea, Methanogenium frigidum and Methanococcoides burtonii Genome Res 13 1580–1588 Occurrence Handle10.1101/gr.1180903 Occurrence Handle1:CAS:528:DC%2BD3sXls1Krur0%3D Occurrence Handle12805271

    Article  CAS  PubMed  Google Scholar 

  • MA Schell M Karmirantzou B Snel D Vilanova B Berger G Pessi MC Zwahlen F Desiere P Bork M Delley RD Pridmore F Arigoni (2002) ArticleTitleThe genome sequence of Bifidobacterium longum reflects its adaptation to the human gastrointestinal tract Proc Natl Acad Sci USA 99 14422–14427 Occurrence Handle10.1073/pnas.212527599 Occurrence Handle1:CAS:528:DC%2BD38XosF2hsrg%3D Occurrence Handle12381787

    Article  CAS  PubMed  Google Scholar 

  • C Schick PA Pemberton GP Shi Y Kamachi S Cataltepe AJ Bartuski ER Gornstein D Bromme HA Chapman GA Silverman (1998) ArticleTitleCross-class inhibition of the cysteine proteinases cathepsins K, L, and S by the serpin squamous cell carcinoma antigen 1: A kinetic analysis Biochemistry 37 5258–5266 Occurrence Handle10.1021/bi972521d Occurrence Handle1:CAS:528:DyaK1cXisVyksrg%3D Occurrence Handle9548757

    Article  CAS  PubMed  Google Scholar 

  • GA Silverman PI Bird RW Carrell FC Church PB Coughlin PGW Gettins JA Irving DA Lomas CJ Luke RW Moyer PA Pemberton E Remold-O’Donnell GS Salvesen J Travis JC Whisstock (2001) ArticleTitleThe serpins are an expanding superfamily of structurally similar but functionally diverse proteins: Evolution, mechanism of inhibition, novel functions, and a revised nomenclature J Biol Chem 276 33293–33296 Occurrence Handle10.1074/jbc.R100016200 Occurrence Handle1:CAS:528:DC%2BD3MXmslymtbc%3D Occurrence Handle11435447

    Article  CAS  PubMed  Google Scholar 

  • M Simonovic PGW Gettins K Volz (2000) ArticleTitleCrystal structure of viral serpin crmA provides insights into its mechanism of cysteine proteinase inhibition Protein Sci 9 1423–1427 Occurrence Handle1:CAS:528:DC%2BD3cXmt1Oms74%3D Occurrence Handle10975564

    CAS  PubMed  Google Scholar 

  • PE Stein RW Carrell (1995) ArticleTitleWhat do dysfunctional serpins tell us about molecular mobility and disease? Nat Struct Biol 2 96–113 Occurrence Handle10.1038/nsb0295-96 Occurrence Handle1:CAS:528:DyaK2MXjsFertLY%3D Occurrence Handle7749926

    Article  CAS  PubMed  Google Scholar 

  • E Stratikos PG Gettins (1999) ArticleTitleFormation of the covalent serpin-proteinase complex involves translocation of the proteinase by more than 70 A and full insertion of the reactive center loop into beta-sheet A Proc Natl Acad Sci USA 96 4808–4813 Occurrence Handle10.1073/pnas.96.9.4808 Occurrence Handle1:CAS:528:DyaK1MXjtVKmsrs%3D Occurrence Handle10220375

    Article  CAS  PubMed  Google Scholar 

  • H Takami Y Takaki I Uchiyama (2002) ArticleTitleGenome sequence of Oceanobacillus iheyensis isolated from the Iheya Ridge and its unexpected adaptive capabilities to extreme environments Nucleic Acids Res 30 3927–3935 Occurrence Handle10.1093/nar/gkf526 Occurrence Handle1:CAS:528:DC%2BD38Xnt1Gmsr0%3D Occurrence Handle12235376

    Article  CAS  PubMed  Google Scholar 

  • JD Thompson TJ Gibson F Plewniak F Jeanmougin DG Higgins (1997) ArticleTitleThe ClustalX windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools Nucleic Acids Res 24 4876–4882 Occurrence Handle10.1093/nar/25.24.4876

    Article  Google Scholar 

  • JC Whisstock R Skinner RW Carrell AM Lesk (2000) ArticleTitleConformational changes in serpins: I. The native and cleaved conformations of α1-antitrypsin J Mol Biol 1 651–665 Occurrence Handle10.1006/jmbi.1999.3375

    Article  Google Scholar 

  • S Ye AL Cech R Belmares RC Bergstrom Y Tong DR Corey MR Kanost EJ Goldsmith (2001) ArticleTitleThe structure of a Michaelis serpin-protease complex Nat Struct Biol 8 979–983 Occurrence Handle10.1038/nsb1101-979 Occurrence Handle1:CAS:528:DC%2BD3MXotlShs74%3D Occurrence Handle11685246

    Article  CAS  PubMed  Google Scholar 

  • BC Yoo K Aoki Y Xiang LR Campbell RJ Hull B Xoconostle-Cazares J Monzer JY Lee DE Ullman WJ Lucas (2000) ArticleTitleCharacterization of Cucurbita maxima phloem serpin-1 (CmPS-1). A developmentally regulated elastase inhibitor J Biol Chem 275 35122–35128 Occurrence Handle10.1074/jbc.M006060200 Occurrence Handle1:CAS:528:DC%2BD3cXotFeitrs%3D Occurrence Handle10960478

    Article  CAS  PubMed  Google Scholar 

  • X Zang RM Maizels (2001) ArticleTitleSerine protease inhibitors from nematodes and the arms race between host and pathogen Trends Biochem Sci 26 191–197 Occurrence Handle10.1016/S0968-0004(00)01761-8 Occurrence Handle1:CAS:528:DC%2BD3MXhs1els7s%3D Occurrence Handle11246026

    Article  CAS  PubMed  Google Scholar 

  • A Zhou RW Carrell JA Huntington (2001) ArticleTitleThe serpin inhibitory mechanism is critically dependent on the length of the reactive center loop J Biol Chem 29 2754 l–27547

    Google Scholar 

Download references

Acknowledgments

We thank Stephen Craft for technical editing of the manuscript, Nishen Naidoo for assistance in production of Fig. 1, and David Briscoe for helpful discussions. Research by N.F.W.S., R.C., and P.M.G.C. is supported by the Australian Research Council.

Author information

Authors and Affiliations

  1. Department of Biological Sciences, Macquarie University, NSW 2109, Australia

    Thomas H. Roberts

  2. Section of Biochemistry and Nutrition, BioCentrum-DTU, Technical University of Denmark, DK-2800, Lyngby, Denmark

    Jørn Hejgaard

  3. School of Biotechnology and Biomolecular Sciences, University of New South Wales, NSW 2052, Australia

    Neil F. W. Saunders & Ricardo Cavicchioli

  4. School of Physics, University of New South Wales, NSW 2052, Australia

    Paul M. G. Curmi

  5. Centre for Immunology, St.Vincent’s Hospital, Darlinghurst, NSW 2010, Australia

    Paul M. G. Curmi

Authors
  1. Thomas H. Roberts
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jørn Hejgaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Neil F. W. Saunders
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ricardo Cavicchioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul M. G. Curmi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas H. Roberts.

Additional information

[Reviewing Editor: Dr. Peer Bork]

Rights and permissions

Reprints and permissions

About this article

Cite this article

Roberts, T.H., Hejgaard, J., Saunders, N.F.W. et al. Serpins in Unicellular Eukarya, Archaea, and Bacteria: Sequence Analysis and Evolution. J Mol Evol 59, 437–447 (2004). https://doi.org/10.1007/s00239-004-2635-6

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00239-004-2635-6

Keywords

Search

Navigation