title: Massive expansion of the calpain gene family in unicellular eukaryotes.
abstract: BACKGROUND
  Calpains are Ca2+-dependent cysteine proteases that participate in a range of crucial cellular processes. Dysfunction of these enzymes may cause, for instance, life-threatening diseases in humans, the loss of sex determination in nematodes and embryo lethality in plants. Although the calpain family is well characterized in animal and plant model organisms, there is a great lack of knowledge about these genes in unicellular eukaryote species (i.e. protists). Here, we study the distribution and evolution of calpain genes in a wide range of eukaryote genomes from major branches in the tree of life.
  
  
  RESULTS
  Our investigations reveal 24 types of protein domains that are combined with the calpain-specific catalytic domain CysPc. In total we identify 41 different calpain domain architectures, 28 of these domain combinations have not been previously described. Based on our phylogenetic inferences, we propose that at least four calpain variants were established in the early evolution of eukaryotes, most likely before the radiation of all the major supergroups of eukaryotes. Many domains associated with eukaryotic calpain genes can be found among eubacteria or archaebacteria but never in combination with the CysPc domain.
  
  
  CONCLUSIONS
  The analyses presented here show that ancient modules present in prokaryotes, and a few de novo eukaryote domains, have been assembled into many novel domain combinations along the evolutionary history of eukaryotes. Some of the new calpain genes show a narrow distribution in a few branches in the tree of life, likely representing lineage-specific innovations. Hence, the functionally important classical calpain genes found among humans and vertebrates make up only a tiny fraction of the calpain family. In fact, a massive expansion of the calpain family occurred by domain shuffling among unicellular eukaryotes and contributed to a wealth of functionally different genes.
authors.affiliation: Microbial Evolution Research Group (MERG), Department of Biology, University of Oslo, OSLO, N-0136, Norway.
authors.forename: Sen
authors.initials: S
authors.lastname: Zhao
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liang
authors.forename: Viktor
authors.initials: V
authors.lastname: Demko
authors.forename: Robert
authors.initials: R
authors.lastname: Wilson
authors.forename: Wenche
authors.initials: W
authors.lastname: Johansen
authors.forename: Odd-Arne
authors.initials: OA
authors.lastname: Olsen
authors.forename: Kamran
authors.initials: K
authors.lastname: Shalchian-Tabrizi
mesh_terms: D001499:Bayes Theorem; D001665:Binding Sites / Q000235:genetics; D002154:Calpain / Q000145:classification / Q000235:genetics*; D016825:Chlamydomonas reinhardtii / Q000201:enzymology / Q000235:genetics; D004748:Entamoeba histolytica / Q000201:enzymology / Q000235:genetics; D005057:Eukaryotic Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D019143:Evolution, Molecular; D014644:Genetic Variation; D008957:Models, Genetic; D010802:Phylogeny; D013045:Species Specificity; D014246:Trichomonas vaginalis / Q000201:enzymology / Q000235:genetics
chemical_list: D002154:Calpain