An embryonic pattern of expression of a human fetal globin gene in transgenic mice

Abstract

During the evolution of the β-globin family gene in vertebrates, different globin genes acquired different developmental patterns of expression. In mammals, specific 'embryonic' β-like globins are synthesized in the earliest erythroid cells, which differentiate in the yolk sac of the embryo. In most mammals the embryonic globin chains are replaced by 'adult' β-globins in fetal and adult erythrocytes, which arise in the liver and bone marrow, respectively. However, in simian primates (including humans), a distinct 'fetal' type of β-like globin chain predominates in fetal erythroid cells 1,2. Based on the pattern of DNA sequence homologies between different mammalian species, these fetal globin genes, Gγ and Aγ, are thought to have descended from an ancestral gene, 'proto-γ', which was embryonic in its pattern of expression3-5. In the mouse, as well as in most other mammalian species, the descendants of the proto-γ gene continue to function as embryonic genes5,6. To investigate the evolutionary changes that led to the 'fetal recruitment' of the γ-globin genes in primates, we have introduced the cloned human Gγ-globin gene into the mouse germ line. We report here that the human Gγ gene reverts to an embryonic pattern of expression in the developing mouse. This observation suggests that during evolution a shift occurred in the timing of expression of a trans-acting signal controlling the proto-γ gene. © 1986 Nature Publishing Group.