Chondrostean sturgeon hepcidin: An evolutionary link between teleost and tetrapod hepcidins

Hepcidin, a cysteine-rich antimicrobial peptide (AMP), plays key roles as a regulatory hormone in iron homeostasis, providing a link between iron metabolism and innate immunity. Unlike many other AMPs displaying a high degree of sequence variability among closely related organisms, hepcidin is highly conserved from teleosts to mammals. However, little is known about the early ancestry of hepcidins in the vertebrate lineage. Here, we first report potential a prototype hepcidin from the Siberian sturgeon Acipenser baerii, a primitive chondrostean species. The A. baerii hepcidin (AbHAMP) gene showed a tripartite exon-intron organization, which encoded a precursor protein comprised of three structural signatures containing eight cysteine residues, a common structure in vertebrate hepcidin genes and proteins. mRNA expression by iron-overloading and bacterial infection and antibacterial activity revealed that AbHAMP might play a role in iron metabolism regulator in the liver, and in direct and/or indirect host immune response in the kidney against invading pathogen. Comparison of gene and protein sequences reveled that AbHAMP possesses intermediate characteristics between tetrapodian and teleostean hepcidins (HAMP1s). Phylogenetically, AbHAMP had a closer genetic affiliation to tetrapodian orthologs than to teleostean orthologs, suggesting that the structures of this chondrostean hepcidin may closely reflect the structures of an evolutionarily ancestral form that might have evolved into extant hepcidins in tetrapods and teleosts, respectively. Based on the identification of hepcidin from the chondrostean group, the emergence of the common ancestral hepcidin should be traced back to in early Osteichthyes: no later than sarcopterygian (lobe-finned fishes) - actinopterygian (ray-finned fishes) split.