Background: Vertebrate alpha (a)- and beta (ß)-globin gene families exemplify the way in which genomes evolve to produce functional complexity. From tandem duplication of a single globin locus, the a- and ß-globin clusters expanded, and then were separated onto different chromosomes. The previous finding of a fossil ß-globin gene (?) in the marsupial a-cluster, however, suggested that duplication of the a-ß cluster onto two chromosomes, followed by lineage-specific gene loss and duplication, produced paralogous a- and ß-globin clusters in birds and mammals. Here we analyse genomic data from an egg-laying monotreme mammal, the platypus (Ornithorhynchus anatinus), to explore haemoglobin evolution at the stem of the mammalian radiation. Results: The platypus a-globin cluster (chromosome 21) contains embryonic and adult a- globin genes, a ß-like ?-globin gene, and the GBY globin gene with homology to cytoglobin, arranged as 5'-?-?'-aD-a3-a2-a1-?-GBY-3'. The platypus ß-globin cluster (chromosome 2) contains single embryonic and adult globin genes arranged as 5'-e-ß-3'. Surprisingly, all of these globin genes were expressed in some adult tissues. Comparison of flanking sequences revealed that all jawed vertebrate a-globin clusters are flanked by MPG-C16orf35 and LUC7L, whereas all bird and mammal ß-globin clusters are embedded in olfactory genes. Thus, the mammalian a- and ß-globin clusters are orthologous to the bird a-and ß-globin clusters respectively. Conclusion: We propose that a- and ß-globin clusters evolved from an ancient MPG-C16orf35-a-ß-GBY-LUC7L arrangement 410 million years ago. A copy of the original ß (represented by ? in marsupials and monotremes) was inserted into an array of olfactory genes before the amniote radiation (>315 million years ago), then duplicated and diverged to form orthologous clusters of ß-globin genes with different expression profiles in different lineages.
Patel, V., Cooper, S., Deakin, J., Fulton, B., Graves, T., Warren, W., ... Marshall Graves, J. (2008). Platypus globin genes and flanking loci suggest a new insertional model for beta-globin evolution in birds and mammals. BMC Biology, 6:34, 1-22. https://doi.org/10.1186/1741-7007-6-34