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

Abstract

The complete nucleotide sequence of a human alpha-globin pseudogene (psi alpha 1) is presented. Comparison of this sequence with a normal human alpha-globin gene (alpha 2) reveals that psi alpha 1 contains both an initiator codon mutation and frameshift deletions which would prevent the production of an alpha-globin polypeptide. psi alpha 1 contains two intervening sequences with sizes and locations characteristic of mammalian alpha-globin genes. However, the alteration or absence of putative splicing sequences suggests that a primary transcript of psi alpha 1 would not be processed to produce a mature mRNA. The relationship of pse alpha 1 to the adjacent duplicated alpha-globin genes alpha 1 and alpha 2 has been investigated at the nucleotide sequence level. psi alpha 1, alpha 2 and alpha 1 each possess the sequence GCCTGTGTGTGCCTG directly following their respective poly(A) addition sites. Sequence analysis of alpha 2 and alpha 1 3' flanking regions further reveals that the alpha-globin gene duplication units are exactly bordered by this homologous sequence. We discuss the possible evolutionary origin of psi alpha 1 and other globin pseudogenes in the context of globin gene duplication.