Evolution of the mouse beta-globin genes: a recent gene conversion in the Hbbs haplotype

We have determined the complete nucleotide sequence of the two nonallelicadult beta-globin genes of the C57BL/10 mouse. These genes, designated betas and beta t, show a sequence similarity of 99.6% over the region borderedby the translational start and stop codons. Both beta s and beta t encodefunctional polypeptide chains that are identical. A comparison of theC57BL/10 beta-globin haplotype, Hbbs, with that of the BALB/c mouse, Hbbd,suggests that the two haplotypes have distinct evolutionary histories. Thetwo adult beta-globin genes of the Hbbd haplotype, beta dmaj and beta dmin,are 16% divergent at the nucleotide level and encode distinct polypeptidesthat are synthesized in differing amounts. Our analysis indicates that agene correction mechanism has been operating on the Hbbs chromosome to keepbeta s and beta t evolving in concert, whereas on the Hbbd chromosome, betadmin has diverged considerably from beta dmaj. We suggest that geneconversion is responsible for the maintained similarity of the Hbbs genes.Furthermore, we attribute the divergence of the Hbbd genes in part to theabsence of a region of simple-sequence DNA within the large interveningsequence of beta dmin. We propose that this region of DNA plays a role infacilitating gene conversion. The deletion of this area in beta dminintroduced a block of nonhomology between the beta dmaj-beta dmin gene pairand thus may have inhibited further gene correction within the Hbbdhaplotype.