A new subfamily of the α-globin-like family has recently been identified in higher primates1-3, rabbit4, galago 5 and possibly the horse6. One member of this subfamily, θ1, is downstream from the adult α1-globin gene. In orang-utan, but not in rabbit4 or galago5, the θ1-gene appears to be structurally intact, suggesting that it may be functional in this species 2. The orang-utan θ1-gene possesses initiation and termination codons, and the predicted polypeptide differs from the orang-utan α1-globin by 55 amino acids. The upstream promoter boxes CCAAT and ATA are present, although approximately 150 base pairs (bp) farther upstream than in the α1-gene. This structural difference in the promoter between the orang-utan θ1- and α1-genes has led Proudfoot7 to speculate that the θ1-gene may be inactive. We have now cloned the θ1-and α1-globin genes from the olive baboon, and have compared their sequences with those of orang-utan. The unique promoter structure of the orang-utan θ1-gene is highly conserved in baboon, although the orang-utan and baboon diverged nearly 30 million years ago. The coding sequences of the two θ1-genes differ by only 6.3% with 22 out of 27 nucleotide substitutions being codon third position silent changes. These data support the view that the θ1-gene has been functional in the baboon, orang-utan, and by implication, in man. We also estimate that the duplication event generating the θ1- and α-globin-like subfamilies may have occurred as much as 260 million years ago.
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