New views of evolution and regulation of vertebrate β-like globin gene clusters from an orphaned gene in marsupials

Few, if any, proteins have been studied in as many organisms as have the hemoglobins. They are found in bacteria, fungi, plants, and animals, serving physiological roles ranging from oxygen transport in the blood of vertebrates to catalyzing the combination of oxygen and nitric oxide to form nitrate in bacteria, yeast, and worms (1, 2). Hence hemoglobins and the globin genes encoding them have been an important system for investigating many biochemical and evolutionary issues. Furthermore, the tissue-specific and developmental regulation of globin gene expression has been studied intensively in mammals and birds. This led to the discovery of many cis-regulatory sequences such as promoters, enhancers, locus control regions (LCRs) (3), and insulators (4). If any model system were well understood both in terms of gene evolution and regulation, this should be the one. However, by their discovery of an orphaned β-like globin gene in marsupials, Wheeler et al. (5) show in a recent issue of PNAS that previously inferred relationships between the β-globin gene clusters in eutherian mammals and birds were oversimplified. The new data force a reconsideration of the evolutionary course of this gene cluster, how these regulatory elements evolved, and how they may be acting today. … the eutherian ɛ-γ-δ-β-globin gene cluster appears to be descended from a different gene cluster from that which led to the avian ρ-β-ɛ cluster.