Nucleotide sequence and expression of rabbit globin genes ζ1, ζ2, and ζ3. Pseudogenes generated by block duplications are transcriptionally competent

The addition of two embryonic globin genes, ζ0 and ζ4, to the rabbit α-like globin gene cluster expands it to include eight genes arranged 5'-ζ0-ζ1-α1-θ1-ζ2-ζ3-θ2-ζ4-3'. The identification of these new genes supports the model that this gene cluster evolved by a series of block duplications of gene sets. The nucleotide sequence of three embryonic ζ-globin genes, ζ1, ζ2, and ζ3, shows that all three are pseudogenes. Gene ζ1 contains two frame-shift deletions, gene ζ2 has lost exon 1 as well as the 5' promoter sequences, and gene ζ3 has lost and replaced codons for amino acids that are critical for the function of α- and ζ-globin polypeptides. However, genes ζ1 and ζ3 are still transcriptionally competent, as shown by the accurate initiation and processing of transcripts from cloned genes introduced into HeLa cells. A quantitative comparison of the ζ-globin gene sequences indicates that the ancestor to the rabbit ζ1 and ζ3 genes was inactivated about 44 million years ago, and the block duplication that formed the two genes occurred about 28 million years ago. About 600 base pairs of the 5'-flanking sequence of the rabbit ζ3-globin gene is very similar to the 5' flanks of three other mammalian ζ-globin genes