Additional copies of genes resulting from two whole genome duplications at the base of the vertebrates have been suggested as enabling the evolution of vertebrate-specific structures such as neural crest, a midbrain/hindbrain organizer and neurogenic placodes. These structures, however, did not evolve entirely de novo, but arose from tissues already present in an ancestral chordate. This review discusses the evolutionary history of co-option of old genes for new roles in vertebrate development as well as the relative contributions of changes in cis-regulation and in protein structure. Particular examples are the FoxD, FGF8/17/18 and Pax2/5/8 genes. Comparisons with invertebrate chordates (amphioxus and tunicates) paint a complex picture with co-option of genes into new structures occurring both after and before the whole genome duplications. In addition, while cis-regulatory changes are likely of primary importance in evolution of vertebrate-specific structures, changes in protein structure including alternative splicing are non-trivial.
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