Dean, M., and Annilo, T. (2005) Evolution of the ATP-Binding Cassette (ABC) Transporter Superfamily in Vertebrates. Annual review of genomics and human genetics. 6:123-142.
The ATP-binding cassette (ABC) superfamily of genes encode membrane proteins that transport a diverse set of substrates across membranes. Mutations in ABC transporters cause or contribute to many different Mendelian and complex disorders including adrenoleukodystrophy, cystic fibrosis, retinal degeneration, hypercholesterolemia, and cholestasis. The genes play important roles in protecting organisms from xenobiotics and transport compounds across the intestine, blood-brain barrier, and the placenta. There are 48 ABC genes in the human genome divided into seven subfamilies based on amino acid sequence similarities and phylogeny. These seven subfamilies are represented in all eukaryotic genomes and are therefore of ancient origin. Sequencing the genomes of numerous vertebrate organisms has allowed the complement of ABC transporters to be characterized and the evolution of the genes to be assessed. Most ABC transporters are conserved in all vertebrates, but there are also several examples of recent duplication and gene loss. For genes with a conserved ortholog, animal models have been identified or developed that can be used to probe the function and regulation of selected genes. Genes that are restricted to a specific group of animals may represent specialized functions that could provide insight into unique biological properties of that organism. Further characterization of all ABC transporters from the human genome and from model organisms will lead to additional insights into normal physiology and human disease.