488-444 million years ago


The early vertebrates improved the junctions between heart muscle cells, developed a truncus arteriosus, innervation of the heart, arteries and veins homologous to those of their jawed descendants, and began to modify an ancestral immune pathway to allow for the clotting of blood.

The cardiac muscle of primitive vertebrates possessed desmosomes and intercalated disks and was more similar to that of higher vertebrates (Hardisty 242). The heart evolved an additional chamber which followed the ventricle, the truncus arteriosus (Hardisty; (Kardong). In larval vertebrates, the pericardial cavity was connected to the coelomic cavity (as in craniates) but the two cavities separated in adulthood (Weichert, 1970). The sinus venosus received nervous input (although the sinus venosus fuses with the right atrium in higher amniotes (Torrey). Chordae tendinae evolved to attach to the atrioventricular valve (Weichert, 1970). Chromaffin-like cells are present in the hearts of both primitive vertebrates and higher vertebrates including mammals. (Webster, 1974, p. 127). Compared to primitive craniates, the early vertebrates underwent a reduction in blood volume, venous sinuses, and venous propulsors, and an increase in blood pressure (Forster, 1997). The dorsal motor nucleus of the vagus nerve contributed to the regulation of the heart (Porges, 1988).

Artery walls contained smooth muscle and collagen and the walls of the aorta also contained elastic fibers. The walls of veins were thinner with less smooth muscle (Hardisty, p. 248). Unpaired arteries from the dorsal aorta serviced the gastrointestinal tract, including the celiac artery (Hardisty 250). The sinus venosus collected blood from the cardinal veins, jugular vein, and the hepatic vein (Kardong). Vagal input to heart and the heart evolved the ability to respond to ACh (Prosser, 1973). There was a further reduction in the number of aortic arches (Kardong)


The blood cells of primitive vertebrates evolved hemoglobin which could transport carbon dioxide and demonstrate the Haldane effect (Hoar, 1983). Of diverse types of white blood cells, neutrophils were typically the most common and basophils the least common (Torrey). Hematopoeisis occured in the pronephros and in the primitive marrow of cartilaginous provertebral arches (Hardisty 251).
Early vertebrates modified existing molecular pathways to promote the clotting of blood. In vertebrates, some of serine proteases possess the amino acid serine at residue 225. This enabled the binding of sodium and novel protein function. Some serine proteases in blood (such as plasmin and clotting factor XIa) possess a proline at site 225 while others such as thrombin, clotting factor Xa (involved in clotting), and complement protein C1r (involved in immunity) possess a serine. Mutations at site 225 drastically affect the function of thrombin (affecting ligand recognition up to 60,000 times). The change in some of the serine proteases needed to acquire a function in coagulation seems to stem from one ancestral mutation changing the amino acid at residue 225 (Guinto,1998; Dang, 1996).
Vertebrate fibrinogen is composed of several subunits in all vertebrates studied (including lampreys). These subunits are homologous, suggesting that a common ancestral gene duplicated to produce the gene and the precursor of the - genes which duplicated subsequently. The ancestral and fibrinogen gene seems to have resulted from gene fusion with an -like fibrinogen gene (the N-terminus) with a second gene homologous to cytotactin and pT49 in humans (the C-terminus) (Henschen, 1983; Weissbach, 1990).