title: The minimal kinome of Giardia lamblia illuminates early kinase evolution and unique parasite biology.
abstract: BACKGROUND
  The major human intestinal pathogen Giardia lamblia is a very early branching eukaryote with a minimal genome of broad evolutionary and biological interest.
  
  
  RESULTS
  To explore early kinase evolution and regulation of Giardia biology, we cataloged the kinomes of three sequenced strains. Comparison with published kinomes and those of the excavates Trichomonas vaginalis and Leishmania major shows that Giardia's 80 core kinases constitute the smallest known core kinome of any eukaryote that can be grown in pure culture, reflecting both its early origin and secondary gene loss. Kinase losses in DNA repair, mitochondrial function, transcription, splicing, and stress response reflect this reduced genome, while the presence of other kinases helps define the kinome of the last common eukaryotic ancestor. Immunofluorescence analysis shows abundant phospho-staining in trophozoites, with phosphotyrosine abundant in the nuclei and phosphothreonine and phosphoserine in distinct cytoskeletal organelles. The Nek kinase family has been massively expanded, accounting for 198 of the 278 protein kinases in Giardia. Most Neks are catalytically inactive, have very divergent sequences and undergo extensive duplication and loss between strains. Many Neks are highly induced during development. We localized four catalytically active Neks to distinct parts of the cytoskeleton and one inactive Nek to the cytoplasm.
  
  
  CONCLUSIONS
  The reduced kinome of Giardia sheds new light on early kinase evolution, and its highly divergent sequences add to the definition of individual kinase families as well as offering specific drug targets. Giardia's massive Nek expansion may reflect its distinctive lifestyle, biphasic life cycle and complex cytoskeleton.
authors.affiliation: Razavi Newman Center for Bioinformatics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. manning@salk.edu
authors.forename: Gerard
authors.initials: G
authors.lastname: Manning
authors.forename: David S
authors.initials: DS
authors.lastname: Reiner
authors.forename: Tineke
authors.initials: T
authors.lastname: Lauwaet
authors.forename: Michael
authors.initials: M
authors.lastname: Dacre
authors.forename: Alias
authors.initials: A
authors.lastname: Smith
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhai
authors.forename: Staffan
authors.initials: S
authors.lastname: Svard
authors.forename: Frances D
authors.initials: FD
authors.lastname: Gillin
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002384:Catalysis; D002453:Cell Cycle; D004260:DNA Repair; D016829:Giardia lamblia / Q000201:enzymology* / Q000235:genetics*; D006639:Histidine / Q000378:metabolism; D010766:Phosphorylation; D010770:Phosphotransferases / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012326:RNA Splicing; D015398:Signal Transduction; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism
chemical_list: D014443:Tyrosine; D006639:Histidine; D010770:Phosphotransferases; D011494:Protein Kinases