Amplification of human argininosuccinate synthetase pseudogenes

Abstract The human genome contains multiple pseudogenes for an argininosuccinate synthetase (AS) gene. To elucidate the molecular mechanisms of generation and dispersion, complete nucleotide sequences of four different AS pseudogenes, ψAS-Y, ψAS-A1, ψAS-A2 and ψAS-A3, have been determined. A comparison of these sequences with those of three reported AS pseudogenes, ψAS-1, ψAS-3 and ψAS-7 revealed that two pairs, ψAS-Y/ψAS-7 and ψAS-A3/ψAS-1, are highly homologous but not identical, thereby suggesting that one of the pairs is generated by a duplication of the other member of the pairs. The ψAS-Y, which is probably located on chromosome Y, and the partially sequenced ψAS-7 are both interrupted by an Alu element at exactly the same site in their 3′-end regions. These two Alu elements are located in an opposite orientation relative to the direction of transcription of the pseudogene, and their possible role on pseudogene dispersion was examined. The ψAS-A1 is also accompanied by an Alu element at its 3′ end. In this case, the orientation of the Alu element is the same as that of the pseudogene. The ψAS-A1 and the Alu element are flanked with direct repeats, as if they had been inserted into a chromosomal site, as a single unit.