Organization and sequence of the gene for the human mitochondrial dicarboxylate carrier: evolution of the carrier family

The dicarboxylate carrier (DIC) is a nuclear-encoded protein located in the mitochondrial inner membrane, It catalyses the transport of dicarboxylates such as malate and succinate across the mitochondrial membrane in exchange for phosphate, sulphate and thiosulphate. We have determined the sequences of the human cDNA and gene for the DIG. The gene sequence was established from overlapping genomic clones generated by PCRs by use of primers and pro bes based upon the human cDNA sequence. It is spread over 8.6 kb of human D NA and is divided into 11 exons. Five short interspersed repetitive Alu seq uences are found in intron I. The protein encoded by the gene is 287 amino acids long. In common with the rat protein, it does not have a processed pr esequence to help to target it into mitochondria. It has been demonstrated by Northern- and Western-blot analyses that the DIC is present in high amou nts in liver and kidney, and at lower levels in all the other tissues analy sed. The positions of introns contribute towards an understanding of the pr ocesses involved in the evolution of human genes for carrier proteins.