After the cloning of the leptin gene in mammals, it took more than a decade to clone teleostean leptin orthologues. The reason of this delay lies in a very low amino acid sequence conservation; depending on the fish species between 13–25% homology compared with human leptin. Despite a dramatic difference in primary sequence, true orthology between
fish and other vertebrate leptins was demonstrated based on conserved gene structure, stable clustering with other vertebrate leptin genes in phylogenetic analyses and conserved tertiary structure when modelled with the human leptin structure.