Evolution of the vertebrate ABC gene family: Analysis of gene birth and death

Abstract

Vertebrate evolution has been largely driven by the duplication of genes that allow for the acquisition of new functions. The ATP-binding cassette (ABC) proteins constitute a large and functionally diverse family of membrane transporters. The members of this multigene family are found in all cellular organisms, most often engaged in the translocation of a wide variety of substrates across lipid membranes. Because of the diverse function of these genes, their large size, and the large number of orthologs, ABC genes represent an excellent tool to study gene family evolution. We have identified ABC proteins from the sea squirt (Ciona intestinalis), zebrafish (Danio rerio), and chicken (Gallus gallus) and, using phylogenetic analysis, identified those genes with a one-to-one orthologous relationship to human ABC proteins. All ABC protein subfamilies found in Ciona and zebrafish correspond to the human subfamilies, with the exception of a single ABCH subfamily gene found only in zebrafish. Multiple gene duplication and deletion events were identified in different lineages, indicating an ongoing process of gene evolution. As many ABC genes are involved in human genetic diseases, and important drug transport phenotypes, the understanding of ABC gene evolution is important to the development of animal models and functional studies.

Molecular analysis and heavy metal detoxification of ABCC1/MRP1 in zebrafish

“…Among these ABC transporters, ABCC1/MRP1 has critical roles in protecting cells from conjugated and unconjugated organic xenobiotics and heavy metals [2,11]. However, functions of ABCC1 in fish are yet to be defined.…”

“…ABC transporters are classified according to their amino acid sequences and organization of functional domains, including hydrophilic ATP-binding domains (also called nucleotide-binding domains, NBDs) and hydrophobic transmembrane domains (TMDs). In humans, more than 48 ABC proteins have been identified and are divided into seven subfamilies, from A to G, based on structural arrangements and phylogenetic analysis [2,3].…”

Molecular characterization and structural implications of 25 new ABCB4 mutations in progressive familial intrahepatic cholestasis type 3 (PFIC3)

“…Molecular ABCB4 analysis in 68 PFIC3 patients D Degiorgio et al paralog ABCB4 gene 13 that, instead of drugs, translocates phosphatidylcholine (PC) from the inner to the outer leaflet of the canalicular membrane of the hepatocyte. The mammalian ABCB4-mediated PC translocation, also known as floppase activity, makes the phospholipids available for extraction into the canalicular lumen by bile salts.…”

Molecular analysis, developmental function and heavy metal-induced expression of ABCC5 in zebrafish

“…ABC transporters are classified according to their amino acid sequences and organization of functional domains, including hydrophilic ATP-binding domains (also called nucleotide-binding domains, NBDs) and hydrophobic transmembrane domains (TMDs). In humans, more than 48 ABC proteins have been identified and are divided into seven subfamilies from A to G, based on structural arrangements and phylogenetic analysis (Dean and Annilo, 2005;Annilo et al, 2006).…”