Evolutionary Analyses of ABC Transporters of Dictyostelium discoideum

Abstract

The ABC superfamily of genes is one of the largest in the genomes of both bacteria and eukaryotes. The proteins encoded by these genes all carry a characteristic 200-to 250-amino-acid ATP-binding cassette that gives them their family name. In bacteria they are mostly involved in nutrient import, while in eukaryotes many are involved in export. Seven different families have been defined in eukaryotes based on sequence homology, domain topology, and function. While only 6 ABC genes in Dictyostelium discoideum have been studied in detail previously, sequences from the well-advanced Dictyostelium genome project have allowed us to recognize 68 members of this superfamily. They have been classified and compared to animal, plant, and fungal orthologs in order to gain some insight into the evolution of this superfamily. It appears that many of the genes inferred to have been present in the ancestor of the crown organisms duplicated extensively in some but not all phyla, while others were lost in one lineage or the other.The common progenitor of plants, animals, fungi, and Dictyostelium discoideum appears to have inherited a large number of genes for transmembrane transporters with related ATPbinding domains from the bacterial ancestor. While bacteria use ABC (ATP-binding cassette) transporters for both import and export, eukaryotes are thought to use them only for export (30). Some of the inherited genes were retained and expanded in one phylum or another, while others were lost. ABC transporters are composed of two copies of the ABC domain with the conserved sequence LSGG recognizable between the Walker A and B motifs of the ATP-binding site (38) and two copies of a transmembrane (TM) domain, usually consisting of six TM helixes (18). These four domains may be present in a single polypeptide or may come from different proteins which associate to form a functional transporter. Many types of molecules, including small ions, lipids, and polypeptides, are transported by ABC transporters (20,41). Eukaryotic ABCs were initially identified as the agents giving rise to multiple drug resistance of neoplastic cells, where they rapidly export compounds used in chemotherapy (14). Since these drugs are unlikely to be encountered naturally, the physiologically relevant functions of ABC transporters are mostly unknown. The ABC family also includes a few genes that carry the ABC domain but have lost the TM portion; their products no longer function as transporters but are likely to carry out other conserved functions.Eukaryotic ABC genes have been classified in seven families, from ABCA to ABCG, based on gene organization and primary sequence homology (20). This classification was established to simplify the naming and identification of the ABC genes, since some had more than one name or had confusing names. At least 68 members of the ABC family can be recognized in the genomic sequences of Dictyostelium discoideum. The predicted products of these genes share a conserved ABC domain of about 200 amino acid residues, which includes an A...

TagA, a putative serine protease/ABC transporter ofDictyosteliumthat is required for cell fate determination at the onset of development

“…While the overall gene structure suggests it is a tag gene, the predicted amino acid sequence of the transporter domain is more similar to mammalian ABCB subfamily transporters than it is to the other tag transporters (Fig. 1D) (Anjard et al, 2002). In the most conserved region of the transporter domain, the NBD, the deduced amino acid sequence of TagA is 53% identical to that of human ABCB1 (MDR1 or P-glycoprotein) and 32% identical across the entire transporter domain.…”

“…1). This class includes the previously characterized tagB, tagC and tagD genes of Dictyostelium that are predicted to encode serine protease/ABC transporter proteins (Shaulsky et al, 1995;Anjard, et al, 2002). While the overall gene structure suggests it is a tag gene, the predicted amino acid sequence of the transporter domain is more similar to mammalian ABCB subfamily transporters than it is to the other tag transporters (Fig.…”

“…Genomic sequence analysis has identified 68 ABC transporter genes from Dictyostelium (Anjard et al, 2002). We carried out a PCR screen of the Dictyostelium genome designed to identify genes of the ABCB transporter subfamily.…”

Phylogeny-wide analysis of social amoeba genomes highlights ancient origins for complex intercellular communication

“…ABC transporters are either present as full transporters with two ATP binding cassettes (ABCs) and two sets of six transmembrane helices or half transporters with one of each (Anjard and Loomis 2002). PP and DF have in total 68 and 64 ABC proteins, respectively.…”

ATP-Binding Cassette Transporter B4 Anchors the Cell Adhesion Molecule DdCAD-1 to Cell Membrane in Dictyostelium discoideum

“…In Dictyostelium, there exist ABC transporters that were involved in the release of signals from cells [15]. 68 members were recognized in Dictyostelium ABC transporter family so far [16], and members of some ABCB families were capable of transporting peptides that lack classical export signals [17]. ABCB4 is a half transporter which contains one transmembrane domain (TMD) and one nucleotide-binding domain (NBD), consisting of six transmembrane segments (Fig.…”