444-416 million years ago


The ancestors of bony fish evolved many new molecules, including prolactin which mammals would use to control milk production, liver cytochrome enzymes, local hormones, and lipoproteins.

The early bony fish developed the hormoneTSH (Hoar, Vol. 2) and possessed two forms of TRH which have been conserved in their descendants (Harder, 2001). The neurohypophysis and adenohypohysis contacted each other (Gorbman, 1995). The hormone prolactin was adapted to perform a variety of functions, including parental behavior and even examples of producing nourishment for young (Hoar, Vol. 2)219-20). N-acetylation of -MSH and -endorphin occured before these hormones were secreted (Dores, 1994). All of the major groups of steroid hormone receptors found in mammals had evolved in ancestral bony fish (Thornton, 2001). Basal actinopterygians, lungfish, amphibians, marsupials, and primitive placental mammals possess two GnRH genes (Fernald, 1999; King, 1995).

Ancestral bony fish developed the first true enamel for teeth (Romer, p. 338). There was a change in the FABPs expressed in the liver (Baba, 1999) and the enzymes sucrase and chymotrypsin were utilized by the digestive system (Stevens). Seventeen of the eighteen families of P450 enzymes present in mammals are also represented in fish (the only exception being the CYP39 family). Of the eighteen families, duplications of the CYP2 family members have produced the greatest diversity (Nelson, 2003). The CYP2J, CYP2N, and CYP2P subfamilies of P450 enzymes function in arachidonic acid metabolism and are members of a clade of P450 enzymes shared between fish and mammals (Oleksiak, 2003).

Many of the genetic changes of the ancestral bony fish would be conserved in their tetrapod descendants. Tight junctions are a chordate feature, although they have also been found in blood-brain and blood-testis barriers in arthropods. Mammals possess about 20 claudin genes which maintain junctions such as the tight junctions of the blood-brain and blood-testis barriers. Many of these genes (and even their intron position) predate the split of bony fish and tetrapods (Kollmar, 2001).
Ancestral bony fish evolved CC cytokines, CC receptors, and CXC receptors are known in bony fish (Magor, 2001; Knaut, 2003).

ApoA-I and ApoE are expressed in yolk sac. The duplication which produced these two genes from an ancestral gene them predates the evolution of bony fish (Babin, 1997). Cytoglobin is the fourth type of globin known in humans, mice, and fish. It is expressed in almost all tissues and appears to be related to vertebrate myoglobin (Hankeln, 2005; DeSantis, 2004).