488-444 million years ago


The early vertebrates evolved a number of additional features such as the ability to regulate their body fluids, kidneys homologous to those of higher vertebrates, additional keratin genes, and more complex signalling mechanisms.

Primitive vertebrates evolved the ability to regulate body osmolarity unlike primitive craniates in which body fluids had similar ion concentrations as seawater (Romer, p. 401). In vertebrates, the mesonephros and metanephros (together called the opistonephros) not segmented after embryonic development (Romer, p. 405). Nephrons developed collecting ducts and increased the efficiency of renal secretion and reabsorbion (Hoar, 1969, Vol. I, p. 99). Vertebrate kidneys assumed some of excretory functions performed by hagfish liver (Hoar, 1969, Vol. I, p. 99).

Vertebrates amplified their number of keratin genes although some of the primitive vertebrates expressed keratin differently than in higher vertebrates. (Fuchs, 1981; Markl, 1989). Although lampreys possess glial cells which are morphologically similar to astrocytes, they lack the intermediate filaments normally expressed in astrocytes (vimentin and GFAP) and express keratins. Lamprey glial cells express keratins in both the brain and spinal cord that are similar to those of the epidermis (Merrick, 1995).

New transcription factors and mechanisms for the control of gene expression evolved in the first vertebrates such as the duplication of Pax genes(Ogasawara, 2000), the duplication of the Dlx gene(Neidert, 2001; Stock, 1996; Graham, 2002), POU class 3 genes (OMIM), a 5th posterior Hox cluster gene (OMIM; Marinez, 1999), and a change in the expression pattern of Pax genes in the pharyngeal arches which may have promoted the formation of jaws (Ogasawara, 2000).

There is a conservation of retinoic acid response elements (RAREs) in vertebrates (Mainguy, 2003).
Clusters of protocadherins are unique to vertebrates (Frank, 2002). The lamins found in vertebrates possess additional domains and an addition of 42 amino acids in one ancestral domain. (Reimer, 1998). Lampreys have a single lactate dehydrogenase gene which has a mixture of characteristics of the two main LDH genes in higher vertebrates: LDH-A in white skeletal muscle and LDH-B in aerobic tissues such as the heart and brain (OMIM).
Vertebrates evolved more complex signaling mechanisms. A duplication of the ancestral gene occurred before lampreys to produce NPY and PYY(Larhammar, 1993). All vertebrates express neuropeptide Y in central and peripheral nervous systems (Larhammar, 1993). Early in vertebrate evolution, additional duplications WNT occurred (Sidow, 1992). There are three GnRH genes known which appear to have resulted from an ancestral gene which was duplicated in ancestral vertebrates. Two of the three resulting decapeptides have the same amino acid sequence in all known species. GnRH3 is known only in fish to date (Fernald, 1999).
Vertebrates utilize small RNA molecules such as 7SK RNP (Bompfunewerer, 2005).and microRNAs (miRNAs) (Bompfunewerer, 2005).