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.

FIG. 1.

Domain arrangements in the ABC families. TM domains are represented by six connected hatched segments. Red ovals, ABCs; R, phosphorylatable regulatory region of ABCA members. The order of the domains in the various proteins is given, but the intervening distances are not drawn to scale. These proteins range from 300 to 2,000 amino acids.

FIG.2.

Clustering of the ABC domains of Dictyostelium proteins. The amino acid sequences of 103 Dictyostelium ABC domains (see the website) were aligned and related to each other. An unrooted tree with bootstrap values is presented, with the values for separation of the families given in boldface. With a single exception (ABCG.20), domains from members of the same family clustered together. The first and second ABC domains in full transporters are marked with a bar to the right and clustered together. The ABC domains from half-transporters found in members of the A, B, and G families also clustered together within their respective families. ABCA.10 and ABCA.11 have only a single ABC domain but may be the first and second ABC domains of a full transporter, respectively. They cluster with the ABC domains of other full transporters of this family.

FIG. 3.

(A) Tree of the ABCA family. The complete amino acid sequences of the ABCA transporters were aligned and related to each other and homologs from other species. In this and other figures, the bootstrap values are presented for unrooted trees. Full transporters with two TM-ABC domains formed a single group that clustered with homologs in Trypanosoma cruzi (Tc), Homo sapiens (Hs), and A. thaliana (At). Two half-transporters clustered with other genes from these organisms as well as one from E. histolytica (Eh). Sequences of genes shown in this and other figures are available on the website (http://www.biology.ucsd.edu/labs/loomis/ABCwebsite/abcfamily.html).(B) Proposed order of gene loss in the ABCA family. The common ancestor of animals, plants, fungi, and Dictyostelium is presumed to have carried a gene encoding a half-transporter as well as one encoding a full transporter. The half-transporter was lost in the line leading to animals and fungi before these two kingdoms diverged. The full transporter was subsequently lost from the progenitor of fungi. Gene losses are indicated by an X.

FIG. 3.

(A) Tree of the ABCA family. The complete amino acid sequences of the ABCA transporters were aligned and related to each other and homologs from other species. In this and other figures, the bootstrap values are presented for unrooted trees. Full transporters with two TM-ABC domains formed a single group that clustered with homologs in Trypanosoma cruzi (Tc), Homo sapiens (Hs), and A. thaliana (At). Two half-transporters clustered with other genes from these organisms as well as one from E. histolytica (Eh). Sequences of genes shown in this and other figures are available on the website (http://www.biology.ucsd.edu/labs/loomis/ABCwebsite/abcfamily.html).(B) Proposed order of gene loss in the ABCA family. The common ancestor of animals, plants, fungi, and Dictyostelium is presumed to have carried a gene encoding a half-transporter as well as one encoding a full transporter. The half-transporter was lost in the line leading to animals and fungi before these two kingdoms diverged. The full transporter was subsequently lost from the progenitor of fungi. Gene losses are indicated by an X.

FIG. 4.

Two possible routes by which the ABCG genes may have arisen. It has been assumed that the original gene in which the ABC domain precedes the TM domain was formed by the fusion of independent regions encoding such domains. Alternatively, a copy of the central region of a preexisting ABC gene could have generated a functional half-transporter. Tandem duplication and fusion of this gene could have generated the full transporters.