Abstract
Lysosomal .beta.-hexaosaminidase (EC 3.2.1.52) is composed of two structurally similar chains, .alpha. and .beta., that are the products of different genes. Mutations in either gene causing .beta.-hexosaminidase deficiency result in the lysosomal storage disease GM2-gangliosidosis. To enable the investigation of the molecular lesions in this disorder and to study the evolutionary relationship between the .alpha. and .beta. chains, the .beta.-chain gene was isolated, and its organization was characterized. The .beta.-chain coding region is divided into 14 exons distributed over .apprxeq. 40 kilobases of DNA. Comparison with the .alpha.-chain gene revealed that 12 of the 13 introns interrupt the coding regions at homologous positions. This extensive sharing of intron placement demonstrates that the .alpha. and .beta. chains evolved by way of the duplication of a common ancestor.