Evolutionary dynamics of the ABCA chromosome 17q24 cluster genes in vertebrates.

ABCA is a subfamily of ATP-binding-cassette (ABC) transporter genes. In this subfamily, it was found that five ABCA genes cluster in a head-to-tail pattern in the human and mouse genomes, but only one was found in fish. To understand better the evolution of this cluster of genes, we screened 11 vertebrate genome sequences and newly identified 28 ABCA cluster genes. Comparative genomic analysis reveals that the ABCA5 gene is relatively evolutionarily conserved. In contrast, the repertoires of the other ABCA genes in this cluster diverge tremendously among species, which is due mainly to postspeciation duplications. In addition, maximum likelihood analysis reveals that positive selection is acting on the paralogous genes ABCA6 and Abca8a, suggesting that these two genes have possibly acquired new functions after duplication. Because most eukaryotic ABC proteins integrate into the cytoplasmic membrane and transport a wide range of substrates across it, we conjecture that newly duplicated ABCA cluster genes are under diversifying selection for the ability to recognize a diverse array of substrates.