Degeneration of an ATP-binding cassette transporter gene, ABCC13, in different mammalian lineages.

The ABC transporter gene family has evolved by a gene "birth-and-death" process; however, the number of ABC pseudogenes in the human genome is surprisingly small. On chromosome 21q11.2, spanning 90 kb, is an ABC gene-like sequence (recently annotated as ABCC13) with the highest similarity to ABCC2. Here we show that while comparative analysis and in silico prediction methods indicate the presence of at least 28 exons, the major ABCC13 transcript in humans consists of only 6 exons with a total length of 1.1 kb. The open reading frame of this transcript is capable of encoding a polypeptide of only 274 amino acids, compared to the more than 1500 amino acids of related ABC transporters. The truncated ABCC13 transcript shows tissue-specific expression, highest in fetal liver, bone marrow, and colon. Since the last exon of the ABCC13 transcript contains an apparent frameshift, we sequenced the respective region from several primates and found that the frameshift is due to an 11-bp deletion that is shared between human, chimpanzee, and gorilla, but is not found in monkeys. In addition, the human ABCC13 gene contains two other frameshift indels in the exons that encode the second nucleotide-binding domain, indicating that ABCC13 is not capable of encoding a functional ABC protein. In an attempt to identify an intact ABCC13 ortholog, we have sequenced the full-length cDNA from rhesus macaque, which contains an open reading frame of 1296 amino acids, producing an apparently functional ABC transporter. Although the mouse and rat genomes contain long-range similarity in the locus where Abcc13 is expected to reside, most of the Abcc13 exons in rodents are degraded below the threshold of sequence homology searches or have been deleted completely.