Molecular evolution and gene expression of ferritin family involved in immune defense of lampreys

Ferritin, one of the key regulators of iron homeostasis, is widely present throughout almost all species. The vertebrate ferritin family, which originates from a single gene in the ancestral invertebrates, contains the widest variety of ferritin subtypes among all animal species. However, the evolutionary history of the vertebrate ferritin family remains to be further clarified. In this study, genome-wide identification of the ferritin homologs is performed in lampreys, which are the extant representatives of jawless vertebrates that diverged from the future jawed vertebrates more than 500 million years ago. Molecular evolutionary analyses show that four members of the lamprey ferritin family, L-FT1-4, are derived from a common ancestor with jawed vertebrate ferritins prior to the divergence of the jawed vertebrate ferritin subtypes. The lamprey ferritin family shares evolutionarily conserved characteristics of the ferritin H subunit with higher vertebrates, but certain members such as L-FT1 additionally accumulate some features of the M or L subunits. Expression profiling reveals that lamprey ferritins are highly expressed in the liver. The transcription of L-FT1 is significantly induced in the liver and heart during lipopolysaccharide stimulation, indicating that L-FTs may play a role in the innate immune response to bacterial infection in lampreys. Furthermore, the transcriptional expression of L-FT1 in quiescent and LPS-activated leukocytes is up- and down-regulated by the lamprey TGF-β2, an essential regulator of the inflammatory response, respectively. Our results provide new insights into the origin and evolution of the vertebrate ferritin family and reveal that lamprey ferritins may be involved in immune regulation as target genes of the TGF-β signaling pathway.