The mouse globin pseudogene βh3 is descended from a premammalian δ-globin gene

The βh3 pseudogene of the BALB/c mouse contains sequence defects which prevent transcription and translation to produce a β-globin. Comparison with other globin gene sequences indicates that βh3 arose by recombination between an adult β-globin gene and some significantly diverged globin sequence. Analysis of noncoding sequences shows that the 3' end of mouse βh3 and the human δ-globin gene are both descended from the ancestral gene, which we call proto-δ. The origin of proto-δ must predate the mammalian radiation. A member of the L1 family of interspersed repetitive elements is inserted into the 3' untranslated δ-homologous sequence in βh3 from BALB/c. βh3 is a widespread feature of the rodent β-globin complex, which has been fixed in the genome for 35 million years. Independent inactivation events produced pseudogenes located between the adult and nonadult β-globin genes in the rodent, primate, rabbit, and goat lineages. One model to explain the abundance and evolutionary persistence of pseudogenes postulates that the mammalian genome simply has no efficient mechanism for deleting nonessential sequences. Consequently, the genomes of higher eukaryotes have been growing, by the accumulation of duplications, with doubling times of 200 ± 100 million years.