Sheep alpha-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 alpha-globin genes (I alpha and II alpha), which are expressed at different levels, the upstream gene being the most efficient. In alpha-globin gene triplication and quadruplication, this trend is confirmed, i.e., the alpha-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-alpha haplotype in which each gene could be recognized for the presence of distinct alleles. The sequence analysis reveals that the bodies of the three alpha-globin genes are essentially identical (99.9% homology) and moreover indicates that the down-regulation of additional alpha-globin genes in sheep is not the effect of sequence variation from the Cap to the Poly(A) addition sites. This striking similarity among alpha-genes is higher than that seen in other mammals and is probably sustained by particularly efficient mechanisms of gene conversion and cross-over fixation.