A globin gene regulatory element discovered in lampreys suggests an ancient origin in ancestral vertebrates. The Miyata et al study of lampreys showed that genes encoding globin polypeptides of the oxygen transporter hemoglobin (HB genes, light orange and red boxes) are adjacent to a ubiquitously expressed NPRL3 gene (violet box) in both major branches of vertebrates, jawed and jawless, despite the separate, convergent evolution of HB genes in each branch, with HB genes in jawless vertebrates more related to CYGB (light orange boxes). Furthermore, an intron of lamprey NPRL3 contains a major regulatory element for globin genes (star), as is the situation in humans. These maps in extant species suggest that the linkage of NPRL3, containing a strong regulatory element, to HB genes occurred in an ancestral vertebrate, represented as Haikouichthys ercaicunensis.10 By hypothesizing multiple ancestral HB genes in the linkage group, one related to CYGB and another related to canonical vertebrate HB (red box), the model can explain convergent evolution of different oxygen-transporting globins as selective expansions of one or the other gene while maintaining strong regulation from the NPRL3 intronic enhancer. Additional genes characteristic of this locus are also shown; boxes above the illustrative DNA helices are transcribed left to right, and those below the DNA are transcribed right to left. The CYBG gene and HB genes are on different chromosomes in humans.