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Journal of Molecular Evolution

, Volume 59, Issue 4, pp 437–447 | Cite as

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

  • Thomas H. Roberts
  • Jørn Hejgaard
  • Neil F. W. Saunders
  • Ricardo Cavicchioli
  • Paul M. G. Curmi
Article

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.

Keywords

Genome Phylogeny Prokaryote Protein fold Reactive-center loop Green alga Codon usage Protostome–deuterostome split Proteinase Protease 

Notes

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.

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Copyright information

© Springer 2004

Authors and Affiliations

  • Thomas H. Roberts
    • 1
  • Jørn Hejgaard
    • 2
  • Neil F. W. Saunders
    • 3
  • Ricardo Cavicchioli
    • 3
  • Paul M. G. Curmi
    • 4
    • 5
  1. 1.Department of Biological SciencesMacquarie UniversityAustralia
  2. 2.Section of Biochemistry and Nutrition, BioCentrum-DTUTechnical University of DenmarkLyngbyDenmark
  3. 3.School of Biotechnology and Biomolecular SciencesUniversity of New South WalesAustralia
  4. 4.School of PhysicsUniversity of New South WalesAustralia
  5. 5.Centre for ImmunologySt.Vincent’s HospitalDarlinghurstAustralia

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