Linkage of the beta-like omega-globin gene to alpha-like globin genes in an Australian marsupial supports the chromosome duplication model for separation of globin gene clusters.

The structure, function, and evolutionary history of globin genes have been the subject of extensive investigation over a period of more than 40 years, yet new globin genes with highly specialized functions are still being discovered and much remains uncertain about their evolutionary history. Here we investigate the molecular evolution of the beta-globin gene family in a marsupial species, the tammar wallaby, Macropus eugenii. We report the complete DNA sequences of two beta-like globin genes and show by phylogenetic analyses that one of these genes is orthologous to embryonically expressed epsilon-globin genes of marsupials and eutherians and the other is orthologous to adult expressed beta-globin genes of marsupials and eutherians. We show that the tammar wallaby contains a third functional beta-like globin gene, omega-globin, which forms part of the alpha-globin gene cluster. The position of omega-globin on the 3' side of the alpha-globin cluster and its ancient phylogenetic history fit the criteria, originally proposed by Jeffreys et al. (1980), of a "fossil" beta-globin gene and suggest that an ancient chromosome or genome duplication preceded the evolution of unlinked clusters of alpha- and beta-globin genes in mammals and avians. In eutherian mammals, such as humans and mice, omega-globin has been silenced or translocated away from the alpha-globin locus, while in marsupials omega-globin is coordinately expressed with the adult alpha-globin gene just prior to birth to produce a functional hemoglobin (alpha2 omega2).