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

Abstract

Previous heteroduplex studies revealed extensive sequence homology between the 2 human adult .alpha.-globin-like genes (.alpha.2 and .alpha.1) and their flanking regions. These homologous regions, which are interrupted by 2 blocks of non-homology, each span .apprx. 4 kilobases. Three kilobases of DNA sequences were determined within and flanking the non-homologous blocks of these 2 tandem duplication units. A total of 3 Alu family repeats was identified. Two of them are .apprx. 300 base pairs long and define the 3'' ends of the 1st homology blocks. The 3rd Alu family member is a 600-base-pair-long sequence consisting of 2 monomeric Alu members arranged in a head-to-tail fashion. It is located in the 3'' portion of the 1st block of nonhomology in .alpha.2-gene-containing unit. Evidently, this dimeric Alu sequence was inserted at a staggered break. The 2nd nonhomology block is the result of insertion or deletion of a 224-base-pair sequence. From these data and the calculation of sequence divergence, a history is proposed for the evolution of the human adult .alpha.-globin-like gene region. DNA insertion elements may disrupt gene correction processes in the 2 duplication units containing .alpha.2- and .alpha.1-globin genes.