Sheep α-globin gene sequences: Implications for their concerted evolution and for the down-regulation of the 3′ genes

In sheep as in man and most other mammals, there are two α-globin genes (Iα and IIα), which are expressed at different levels, the upstream gene being the most efficient. In α-globin gene triplication and quadruplication, this trend is confirmed, i.e., the α-chain output of the downstream genes progressively decreases. In this study, we have determined the complete sequence of the cDNAs and of both the introns in a triple-α haplotype in which each gene could be recognized for the presence of distinct alleles. The sequence analysis reveals that the bodies of the three α-globin genes are essentially identical (99.9% homology) and moreover indicates that the down-regulation of additional α-globin genes in sheep is not the effect of sequence variation from the Cap to the Poly(A) addition sites. This striking similarity among α-genes is higher than that seen in other mammals and is probably sustained by particularly efficient mechanisms of gene conversion and cross-over fixation.