The structure of a human α-globin pseudogene and its relationship to α-globin gene duplication

Abstract The complete nucleotide sequence of a human α-globin pseudogene (ψα1) is presented. Comparison of this sequence with a normal human α-globin gene (α2) reveals that ψα1 contains both an initiator codon mutation and frameshift deletions which would prevent the production of an α-globin polypeptide. ψα1 contains two intervening sequences with sizes and locations characteristic of mammalian α-globin genes. However, the alteration or absence of putative splicing sequences suggests that a primary transcript of ψα1 would not be processed to produce a mature mRNA. The relationship of ψα1 to the adjacent duplicated α-globin genes α1 and α2 has been investigated at the nucleotide sequence level. ψα1, α2 and α1 each possess the sequence GCCTGTGTGTGCCTG directly following their respective poly(A) addition sites. Sequence analysis of α2 and α1 3′ flanking regions further reveals that the α-globin gene duplication units are exactly bordered by this homologous sequence. We discuss the possible evolutionary origin of ψα1 and other globin pseudogenes in the context of globin gene duplication.

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