Insert-containing neurotrophins in teleost fish and their relationship to nerve growth factor.

Some teleost species express neurotrophins not known in other vertebrates, namely neurotrophin-6 (NT-6) and neurotrophin-7 (NT-7). Mature proteins of both genes are closely related to nerve growth factor (NGF). We have cloned zebrafish NGF (zNGF) and show that genomic organization and transcript structure of zNGF, zNT-7, and mouse NGF are highly similar. This suggests the vital importance of hitherto unrecognized untranslated regions and principal features of gene structure, retained in species separated 410 mya. Aiming to clarify the relation between NT-6 and NT-7, we have identified partial NGF and NT-6/7 sequences of additional teleost species and a complete set of neurotrophins in two pufferfish genomes (fugu and tetraodon). Interestingly, this includes neurotrophin-4/5, hitherto not described in any fish species. Identification of only one NT-6/7-like gene in pufferfish and salmon, phylogenetic analysis and a strikingly high identity of an untranslated sequence of zNT-7 and the pufferfish NT-6/7 genes strongly suggest that these genes have evolved from a common ancestor after a single "fish specific" duplication of NGF. Evidence for sub- and neofunctionalization is provided.