Comparison of cloned mouse α- and β-globin genes: Conservation of intervening sequence locations and extragenic homology

Abstract

The authors have cloned and characterized a 9.7-kilobase EcoRI fragment of mouse DNA that contains an α-globin gene. The gene is encoded in at least three discontinuous segments of DNA interrupted by two small intervening sequences that can be visualized as R-loop structures in the electron microscope. The size of the gene and its small intervening sequences fits well with the known size of the α-globin mRNA precursor, suggesting that these intervening sequences, like those of β-globin, are transcribed. Partial sequence analysis indicates that the larger intervening sequence interrupts the α-globin gene at a site exactly corresponding to that interrupted by the larger intervening sequences in both the β-globin major and minor genes. This observation suggests that these sequences were present when the α- and β-globin genes diverged in early vertebrate evolution, more than 500 million years ago. Furthermore, though α and β(maj) genes are encoded on different chromosomes, when their sequences are compared directly by visualization of heteroduplex structures, only one 150- to 200-base-pair segment of homology is recognized. These homologous sequences are located on the 3'-flanking segments of both genes, about 1.5 kilobases from each.