Fig. 3.

An evolutionary model describing the independent evolution of erythroid-specific O₂ transport Hbs in gnathostomes and cyclostomes. The gnathostomes are here represented by amniotes, amphibians, and teleost fish. According to this model, the duplication of an ancestral, single-copy globin gene in the stem lineage of vertebrates produced one descendant gene lineage that eventually gave rise to the α- and β-Hbs of gnathostomes (left branch) and another gene lineage that gave rise to the common ancestor of Mb, Cygb, and cyclostome Hb (right branch). In the latter gene lineage, a subsequent duplication before the vertebrate radiation gave rise to Mb (which was secondarily lost in cyclostomes) and Cygb (= cyclostome Hb). In the gnathostome and cyclostome Hb gene lineages, independent origins of O₂ transport functions are denoted by orange lines. In the case of gnathostome Hb, cooperativity of O₂ binding stems from oxygenation-linked transitions in quaternary structure of an α₂β₂ heterotetramer. The origin of cooperativity and allosteric regulation was preceded by duplication and divergence of the proto α- and β-globin genes. In the case of cyclostome Hb, cooperativity stems from oxygenation-linked dissociation of multimers into ligated monomers. The O₂ transport function of gnathostome Hb preceded the divergence of cartilaginous fish from the ancestor of teleosts and tetrapods approximately 500 mya (48, 78), and the O₂ transport function of cyclostome Hb preceded the divergence between representatives of the two extant cyclostome subclasses, Myxini and Hyperoartia, approximately 450 mya (49). Thus, the convergent evolution of erythroid-specific O₂ transport Hbs appears to have occurred in the early Paleozoic (approximately 450–600 mya), after the split between gnathostomes and cyclostomes, but before the split between cartilaginous fish and the ancestor of teleosts and tetrapods and before the split between hagfish and lamprey. Estimated divergence dates are taken from Hedges (78).