We have determined the complete nucleotide sequence of beta h2, a pseudogene in the mouse beta-globin gene complex. The structure of beta h2 is analogous to that of a normal beta-globin gene, and its nucleotide sequence shares 72% homology with the coding regions of a reference mouse adult beta-globin gene. A frame shift occurs in the first coding region for which a compensatory splicing scheme can be devised. The reading frame is not otherwise disrupted. All of the recognized transcription, translation, and splicing signals in beta h2 are intact, with the exception of the " CCAAT box," which has been altered to GTAAC . We compared the predicted amino acid sequence of beta h2 with other beta-globin sequences. Evidence for a period of divergence without selection in the history of beta h2 was found in a set of codons that are usually highly conserved in productive beta-globin genes. An evolutionary tree constructed from nucleotide sequence suggests that beta h2 originated from the adult genes at least 60 million years ago. After some period as a productive gene, beta h2 was inactivated and has subsequently diverged without selection. Hybridization experiments demonstrated that beta h2 and the surrounding region occur without major alteration in other rodent species. The sequence ( AGCCA - 4n - GTGT ) occurs 5' of the CCAAT box in beta h2 and in many productive globin genes
