The Evolution Of ABCA Subfamily In Chordates

The ATP-binding cassette (ABC) superfamily of genes encodes membrane proteins that transport many kinds of substrates across membranes. Based on amino acid sequence similarities and phylogenetic analysis, 48 ABC genes in the human genome were divided into seven subfamilies: ABCA to ABCG that were found in all vertebrates. Compared to other subfamilies, the ABCA gene family has undergone higher rate of gene duplication and loss during evolution.The dynamic pattern of ABCA subfamily evolution may be mainly caused by the extensive expansion and subsequent gene loss in a cluster of vertebrate ABCA genes. In human beings, this gene cluster contains five ABCA genes, but just single gene, an ABCA5 ortholog, was observed in fish genome. When this cluster genes expanded during vertebrate evolution and what evolutionary forces have acted on the newly duplicated genes? To address above questions, we screened 9 other vertebrate genome sequences and found: 1. This gene cluster is consisted of 5 ABCA genes in all detected mammals, but dog ABCA10 is a pseudogene. Chicken (Gallus gallus) and frog (Xenopus tropicalis) have 3 and 4 genes in the cluster respectively, whereas only one gene was identified in other two fish consistent with that of zebrafish. 2. All ABCA5 genes from different taxa form one monophyletic clade and the other genes (hereafter called"non-ABCA5 genes") from all vertebrates form another monophyletic clade, indicating that the origin of ABCA5 occurred before the vertebrate radiation, whereas the non-ABCA5 genes occurred after the split of tetrapods and teleosts. 3. The non-ABCA5 genes rapidly duplicated in tetrapods in a lineage-specific pattern and formed lineage-specific clades in the phylogenetic tree. For example, placental-specific and marsupial-specific clades were found in addition to the frog-specific and chicken-specific duplications. 4. Positive selection is operating on the non-ABCA5 genes and the positively selected sites maily locate in C-TMD. 5. Positive selection is acting on paralogous ABCA6 and ABCA8a, suggesting that these two genes have possibly acquired new functions after duplication.To further clarify the evolution of ABCA subfamily in other species and when the...