title: Evolutionary implications of the mosaic pyrimidine-biosynthetic pathway in eukaryotes.
abstract: The de-novo pyrimidine biosynthetic pathway involves six enzymes, in order from the first to the sixth step, carbamoyl-phosphate synthetase II (CPS II) comprising glutamine amidotransferase (GAT) and carbamoyl-phosphate synthetase (CPS) domains or subunits, aspartate carbamoyltransferase (ACT), dihydroorotase (DHO), dihydroorotate dehydrogenase (DHOD), orotate phosphoribosyltransferase (OPRT), and orotidine-5'-monophosphate decarboxylase (OMPDC). In contrast with reports on molecular evolution of the individual enzymes, we attempted to draw an evolutionary picture of the whole pathway using the protein phylogeny. We demonstrate highly mosaic organizations of the pyrimidine biosynthetic pathway in eukaryotes. During evolution of the eukaryotic pathway, plants and fungi (or their ancestors) in particular may have secondarily acquired the characteristic enzymes. This is consistent with the fact that the organization of plant enzymes is highly chimeric: (1) two subunits of CPS II, GAT and CPS, cluster with a clade including cyanobacteria and red algal chloroplasts, (2) ACT not with a cyanobacterium, Synechocystis spp., irrespective of its putative signal sequence targeting into chloroplasts, and (3) DHO with a clade of proteobacteria. In fungi, DHO and OPRT cluster respectively with the corresponding proteobacterial counterparts. The phylogenetic analyses of DHOD and OMPDC also support the implications of the mosaic pyrimidine biosynthetic pathway in eukaryotes. The potential importance of the horizontal gene transfer(s) and endosymbiosis in establishing the mosaic pathway is discussed.
authors.affiliation: Department of Parasitology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, 113-8421, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nara
authors.forename: T
authors.initials: T
authors.lastname: Hshimoto
authors.forename: T
authors.initials: T
authors.lastname: Aoki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001221:Aspartate Carbamoyltransferase / Q000235:genetics; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000235:genetics; D004080:Dihydroorotase / Q000235:genetics; D000090722:Dihydroorotate Dehydrogenase; D005057:Eukaryotic Cells / Q000201:enzymology / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D009962:Orotate Phosphoribosyltransferase / Q000235:genetics; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010802:Phylogeny; D011743:Pyrimidines / Q000096:biosynthesis*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D000090722:Dihydroorotate Dehydrogenase; D011743:Pyrimidines; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D001221:Aspartate Carbamoyltransferase; D009962:Orotate Phosphoribosyltransferase; D004080:Dihydroorotase; D009964:Orotidine-5'-Phosphate Decarboxylase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); C030986:pyrimidine