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 expression^3–5. In the mouse, as well as in most other mammalian species, the descendants of the proto-γ gene continue to function as embryonic genes^5,6. 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.