title: Inferring protein function from genomic sequence: Giardia lamblia expresses a phosphatidylinositol kinase-related kinase similar to yeast and mammalian TOR.
abstract: Functional assays of genes have historically led to insights about the activities of a protein or protein cascade. However, the rapid expansion of genomic and proteomic information for a variety of diverse taxa is an alternative and powerful means of predicting function by comparing the enzymes and metabolic pathways used by different organisms. As part of the Giardia lamblia genome sequencing project, we routinely survey the complement of predicted proteins and compare those found in this putatively early diverging eukaryote with those of prokaryotes and more recently evolved eukaryotic lineages. Such comparisons reveal the minimal composition of conserved metabolic pathways, suggest which proteins may have been acquired by lateral transfer, and, by their absence, hint at functions lost in the transition from a free-living to a parasitic lifestyle. Here, we describe the use of bioinformatic approaches to investigate the complement and conservation of proteins in Giardia involved in the regulation of translation. We compare an FK506 binding protein homologue and phosphatidylinositol kinase-related kinase present in Giardia to those found in other eukaryotes for which complete genomic sequence data are available. Our investigation of the Giardia genome suggests that PIK-related kinases are of ancient origin and are highly conserved.
authors.affiliation: Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, 7 MBL Street, Woods Hole, MA 02543-1015, USA. morrison@mbl.edu
authors.forename: Hilary G
authors.initials: HG
authors.lastname: Morrison
authors.forename: Gus
authors.initials: G
authors.lastname: Zamora
authors.forename: Robert K
authors.initials: RK
authors.lastname: Campbell
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Sogin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D018797:Cell Cycle Proteins; D016208:Databases, Factual; D005057:Eukaryotic Cells; D017125:Genes, Protozoan / Q000502:physiology*; D018503:Genome, Protozoan; D016829:Giardia lamblia / Q000201:enzymology*; D006801:Humans; D008666:Metalloendopeptidases; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D010802:Phylogeny; D011494:Protein Kinases / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D022061:Tacrolimus Binding Protein 1A / Q000235:genetics*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D008666:Metalloendopeptidases; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011494:Protein Kinases; D015800:Protozoan Proteins; D029701:Saccharomyces cerevisiae Proteins; D022061:Tacrolimus Binding Protein 1A; D022021:Tacrolimus Binding Proteins; C083324:TOR1 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae; C070738:O-sialoglycoprotein endopeptidase