Origin of gene overlap: The case of TCP1 and ACAT2

The human acetyl-CoA acetyltransferase 2 gene, ACAT2, codes for a thiolase, an enzyme involved in lipid metabolism. The human T-complex protein 1 gene , TCP1, encodes a molecular chaperone of the chaperonin family. The two gen es overlap by their 3'-untranslated regions, their coding sequences being l ocated on opposite DNA strands in a tail-to-tail orientation. To find out h ow the overlap might have arisen in evolution, the homologous genes of the zebrafish, the African toad, caiman, platypus, opossum, and wallaby were id entified. In each species, standard or long polymerase chain reactions were used to determine whether the ACAT2 and TCP1 homologs are closely linked a nd, if so, whether they overlap. The results reveal that the overlap appare ntly arose during the transition from therapsid reptiles to mammals and has been retained for >200 million years. Part of the overlapping untranslated region shows remarkable sequence conservation. The overlap presumably aros e during the chromosomal rearrangement that brought the two unrelated and p reviously separated genes together. One or both of the transposed genes fou nd by chance signals that are necessary for the processing of their transcr ipts to be present on the noncoding strand of the partner gene.