Unusual alpha-globin-like gene that has cleanly lost both globin intervening sequences

Abstract

We have cloned and determined the nucleotide sequence of a mouse alpha-globin-like gene that entirely lacks the two intervening sequences that interrupt all globin genes thus far examined. The fact that this gene, alpha-3, is closely homologous to the normal adult alpha gene sequence suggests that it arose after the alpha/beta divergence and that it therefore must have lost its intervening sequences. The further fact that these intervening sequences have been lost cleanly--that is, in according with the G-T/A-G splicing rule of RNA--suggests, among other possibilities, that their loss may have been brought about by a gene conversion event involving the mediation of mature globin mRNA or its cDNA cognate. We propose such a mechanism that would permit the loss of either or both intervening sequences independently. Only the loss of both, however, should result in the inactivation of the globin gene, as seems to be the case with alpha-3.