444-416 million years ago
The ancestors of bony fish also evolved greater complexity in their immune system, a basic coagulation cascade, hormonal mechanisms to regulate blood vessels, and urinary bladders in both genders.
The enzyme eosinophil peroxidase (whose activity is weak or absent in cartilaginous fish) became part of the innate immune defenses of early bony fish (Hine, 1990). Early bony fish evolved true lymphatic vessels, lined by endothelium to replace the ancestral lymphatic sinuses (Dutta, 371; Dehal, 2002; Torrey, 1979; Romer). Early bony fish evolved natural killer cell receptors encoded in a leukocyte receptor cluster region (Yoder, 2001; Sato, 2003). The Ia set of MHC genes are known as classical loci and are the major determinants of antigen presentation. Classical MHC proteins are present in bony fish and are expressed on similar cell types as those in higher vertebrates (Dijkstra, 2003). Interferons are definitely known from amniotes and possible homologs have also been identified in fish (Magor, 2001).
The ancestral bony fish evolved hormonal responses by blood vessels which are conserved in their descendants. For example, both the gill vessels of fish and lung vessels of amphibians are constricted by Ach and dilated by epinephrine; in fish and mammals epinephrine dilates coronary arteries and constricts most systemic arteries (Prosser, p. 831). The GATA family of transcription factors which is so important in mammalian hematopoeisis evolved in ancestral bony fish (or perhaps earlier point)(Lyons, 2002). Bony fish initiated the regulation of the heart by the spinal sympathetic nervous system (Porges, 1988). The response of the cells of the bowfin aorta to bradykinin is comparable to those of mammals. There is only one amino acid difference between the forms of bradykinin in humans and bowfins (Conlon, 1995).
The early bony fish modified their urinary systems to include a bladder
in both males and females (Romer, p. 416), JG cells in nephrons (Hoar,
1969, Vol. I, p. 97), and an intermediate segment of renal tubule (Hoar,
1969, Vol. I).