Comparative genomics and adaptive selection of the ATP-binding-cassette gene family in caenorhabditis species

Abstract

ABC transporters constitute one of the largest gene families in all species. They are mostly involved in transport of substrates across membranes. We have previously demonstrated that the Caenorhabditis elegans ABC family shows poor one-to-one gene orthology with other distant model organisms. To address the evolution dynamics of this gene family among closely related species, we carried out a comparative analysis of the ABC family among the three nematode species C. elegans, C. briggsae, and C. remanei. In contrast to the previous observations, the majority of ABC genes in the three species were found in orthologous trios, including many tandemly duplicated ABC genes, indicating that the gene duplication took place before speciation. Species-specific expansions of ABC members are rare and mostly observed in subfamilies A and B. C. briggsae and C. remanei orthologous ABC genes tend to cluster on trees, with those of C. elegans as an outgroup, consistent with their proposed species phylogeny. Comparison of intron/exon structures of the highly conserved ABCE subfamily members also indicates a closer relationship between C. briggsae and C. remanei than between either of these species and C. elegans. A comparison between insect and mammalian species indicates lineage-specific duplications or deletions of ABC genes, while the family size remains relatively constant. Sites undergoing positive selection within subfamily D, which are implicated in very-long-chain fatty acid transport, were identified. The evolution of these sites might be driven by the changes in food source with time.

Figure 1.—

Maximum-likelihood protein trees of ABC genes from subfamily A (A) and subfamily D (B). The two subfamilies were chosen to show nematode ABC genes with or without species-specific clustering in the phylogenetic trees. Those genes in a clade consisting of one ABC gene from each nematode species are defined orthologs. Members from nematode, insect, and mammalian species are green, blue, and red, respectively. Numbers on the branch nodes indicate the percentage of bootstrap support from 500 replicates. Genes marked by stars probably have an unpredicted ortholog in the related species on the basis of TBLASTN searches (data not shown). Genes in nematodes that are not one-to-one orthologs to C. elegans are named by subfamily and numbered and prefixed by br| and rm| (C. briggsae and C. remanei, respectively). #, a small-sized ABCA member unique in C. elegans; el|, C. elegans; dp|, D. pseudoobscura; dm|, D. melanogaster; mm|, Mus musculus; hs|, H. sapiens.

Figure 1.—

Maximum-likelihood protein trees of ABC genes from subfamily A (A) and subfamily D (B). The two subfamilies were chosen to show nematode ABC genes with or without species-specific clustering in the phylogenetic trees. Those genes in a clade consisting of one ABC gene from each nematode species are defined orthologs. Members from nematode, insect, and mammalian species are green, blue, and red, respectively. Numbers on the branch nodes indicate the percentage of bootstrap support from 500 replicates. Genes marked by stars probably have an unpredicted ortholog in the related species on the basis of TBLASTN searches (data not shown). Genes in nematodes that are not one-to-one orthologs to C. elegans are named by subfamily and numbered and prefixed by br| and rm| (C. briggsae and C. remanei, respectively). #, a small-sized ABCA member unique in C. elegans; el|, C. elegans; dp|, D. pseudoobscura; dm|, D. melanogaster; mm|, Mus musculus; hs|, H. sapiens.

Figure 2.—

Schematic of tandemly duplicated full-sized subfamily B genes present in syntenic regions in the three nematode species. (Top, middle, and bottom) Gene clusters in C. elegans, C. briggsae, and C. remanei, respectively. In C. elegans, the genes on the left and the right form two four-gene clusters while the two in the middle form a single two-gene cluster. The C. elegans genes in the left cluster are not orthologous to those in C. briggsae and C. remanei in the phylogenetic tree. The clusters are arranged by their order on chromosome X. Solid and open boxes represent ABC domains in the amino terminus and carboxyl terminus, respectively. Gene orientation is indicated by arrows. Solid and open triangles denote a reverse transcriptase gene and a transposase-like gene identified in the middle of the two C. briggsae four-gene clusters, respectively. br|F22E10.1 is in reverse orientation as opposed to F22E10.1(pgp-12). A residual ABC domain is found at the end of the C. briggsae syntenic region, which could be a remnant pseudogene (on the left).

Figure 3.—

Exon/intron structure of the single ABCE gene from the three nematode species. Syntenic genomic regions in C. briggsae and C. remanei centering on the Y39E4B.1 were used as input for FGENESH (Salamov and Solovyev 2000) using default parameters. The exon/intron size and positions were extracted from FGENESH output to draw the diagram. CE, Y39E4B.1; CB, br|Y39E4B.1; CR, rm|Y39E4B.1.

Figure 4.—

Distribution of positive selection sites (BEB probability >0.85) mapped onto the secondary structure of ABCD proteins. The ABCD gene C44B7.9 was used as the reference ABCD (see materials and methods). The ABC and TM domains were predicted by Pfam (Bateman et al. 2002) and TMHMM (Krogh et al. 2001), respectively. The open arrowheads denote positive selection sites. N, amino terminus; C, carboxyl terminus; ABC, ABC signature motif.