Sequence organization and genomic complexity of primate θ1 globin gene, a novel α-globin-like gene

The α-like and β-like globin genes have provided a paradigm for the study of molecular evolution and regulation of multigene families in eukaryotes. The human α-globin gene cluster, which is on chromosome 16 (ref. 1), consists of six genes arranged in the order^2-5 5′-ζ(embryonic)-ψζ-ψα2-ψα1- α2(adult)-α1(adult)-3′. DNA sequencing data have demonstrated that ζ (ref. 6) and α2 (or α1, refs 7-9) are the embryonic and adult genes, respectively, while ψζ (ref. 6), ψα2 (ref. 5) ψα1 (ref. 10) are all inactive pseudogenes. Restriction mapping analysis has shown that the structure of this locus in several anthropoid primates is nearly identical to that of the human^11,12. Recently, we have isolated the adult α-globin gene region from orang-utan, olive baboon and rhesus macaque by molecular cloning. We report here the complete nucleotide sequence of a gene located immediately downstream from the adult α1-globin gene of the orang-utan, along with its flanking DNA. We designate this gene as θ1, and show that it contains the essential sequence elements required for an expressive gene. The putative polypeptide is 141 amino acids long, identical to that of the α- or ζ-globin, but its predicted amino-acid sequence is nearly as different from the orang-utan α-globin (55 differences) as the human ζ-globin is from the human α-globin (59 differences), suggesting an ancient history for the θ1 -globin gene. Results of blot hybridization experiments using the cloned orang-utan θ1 gene sequence as probe demonstrate a similar α2-α1-θ1 linkage map existing in the human genome. Furthermore, multiple copies of sequences homologous to the θ1 gene are detected in both human and orang-utan. These results cast a new light on the primate α-globin gene family, and have intriguing implications for the existence of previously unreported, functional globin-like gene(s) in the primate genomes.