The evolution and sequence comparison of two recently diverged mouse chromosomal beta--globin genes

We have determined the entire nucleotide sequence of a cloned mouse beta--globinminor gene and compared it to the closely related sequence of the betamajor gene. These two genes differ by nine amino acids and presumably evolved from a common ancestral gene as recently as 50 million years ago. Since these genes are closely linked and coordinately expressed, they provide an especially favorable opportunity to assess selection and mutation as these processes affect genes under similar constraints. We find that evolution has preserved these two genes in two short segments of DNA which include their immediately adjacent flanking regions. These regions presumably encode functions that are necessary for proper globin gene expression. In contrast, the more distal flanking sequences and major segments of the long intervening sequences have diverged much more sharply. The homology pattern in these genes also provides considerable insight into the mechanisms by which less constrained nucleotide sequences diverge rapidly. Change in such regions apparently occurs less by point mutation than by insertion, deletion and duplication of relatively short segments of the genome.