title: Phylogenetic analysis of glycerol 3-phosphate acyltransferases in opisthokonts reveals unexpected ancestral complexity and novel modern biosynthetic components.
abstract: Glycerolipid synthesis represents a central metabolic process of all forms of life. In the last decade multiple genes coding for enzymes responsible for the first step of the pathway, catalyzed by glycerol 3-phosphate acyltransferase (GPAT), have been described, and characterized primarily in model organisms like Saccharomyces cerevisiae and mice. Notoriously, the fungal enzymes share low sequence identity with their known animal counterparts, and the nature of their homology is unclear. Furthermore, two mitochondrial GPAT isoforms have been described in animal cells, while no such enzymes have been identified in Fungi. In order to determine if the yeast and mammalian GPATs are representative of the set of enzymes present in their respective groups, and to test the hypothesis that metazoan orthologues are indeed absent from the fungal clade, a comparative genomic and phylogenetic analysis was performed including organisms spanning the breadth of the Opisthokonta supergroup. Surprisingly, our study unveiled the presence of 'fungal' orthologs in the basal taxa of the holozoa and 'animal' orthologues in the basal holomycetes. This includes a novel clade of fungal homologues, with putative peroxisomal targeting signals, of the mitochondrial/peroxisomal acyltransferases in Metazoa, thus potentially representing an undescribed metabolic capacity in the Fungi. The overall distribution of GPAT homologues is suggestive of high relative complexity in the ancestors of the opisthokont clade, followed by loss and sculpting of the complement in the descendent lineages. Divergence from a general versatile metabolic model, present in ancestrally deduced GPAT complements, points to distinctive contributions of each GPAT isoform to lipid metabolism and homeostasis in contemporary organisms like humans and their fungal pathogens.
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Heather C
authors.initials: HC
authors.lastname: Smart
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Fred D
authors.initials: FD
authors.lastname: Mast
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Maxwell F J
authors.initials: MF
authors.lastname: Chilije
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Marjan
authors.initials: M
authors.lastname: Tavassoli
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Dacks
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Vanina
authors.initials: V
authors.lastname: Zaremberg
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D055162:Biocatalysis; D004721:Endoplasmic Reticulum / Q000201:enzymology; D056890:Eukaryota / Q000201:enzymology*; D005658:Fungi / Q000201:enzymology; D020440:Gene Duplication; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000737:chemistry / Q000378:metabolism*; D006017:Glycolipids / Q000096:biosynthesis*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology; D008954:Models, Biological; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D006017:Glycolipids; D007527:Isoenzymes; D005992:Glycerol-3-Phosphate O-Acyltransferase