Molecular evolution of the human adult α-globin-like gene region: Insertion and deletion of Alu family repeats and non-Alu DNA sequences

Previous heteroduplex studies have revealed extensive sequence homology between the two human adult α-globin-like genes (α2 and α1) and their flanking regions. These homologous regions, which are interrupted by two blocks of nonhomology, each span approximately 4 kilobases. We have determined 3 kilobases of DNA sequences within and flanking the nonhomologous blocks of these two tandem duplication units. A total of three Alu family repeats has been identified. Two of them are approximately 300 base pairs long and define the 3' ends of the first homology blocks. The third Alu family member is a 600-base-pair-long sequence consisting of two monomeric Alu members arranged in a head-to-tail fashion. It is located in the 3' portion of the first block of nonhomology in α2-gene-containing unit. We present direct evidence that this dimeric Alu sequence was inserted at a staggered break. The second nonhomology block is the result of insertion or deletion of a 224-base-pair sequence. From these data and the calculation of sequence divergence, we propose a history for the evolution of the human adult α-globin-like gene region. We also suggest that DNA insertion elements may disrupt gene correction processes in the two duplication units containing α2- and α1-globin genes.