Fgf evolution in vertebrates: insights from cyclostomes

Fibroblast growth factors (FGFs) are crucial for animal development, growth and physiological regulation. Early vertebrate evolution was shaped by complex whole-genome duplications (WGDs); after a shared first event (1R V ), jawed vertebrates underwent a second distinct WGD (2R JV ), while cyclostomes (lampreys and hagfishes) experienced a different, lineage-specific genome expansion (2R CY ). Despite their key evolutionary position, the FGF gene family in cyclostomes has remained largely uncharacterized, contrasting with extensive research in jawed vertebrates and their invertebrate chordate relatives. To illuminate this knowledge gap, we conducted a comprehensive genomic survey of FGF genes across four cyclostome species, five jawed vertebrates, and an amphioxus outgroup, leveraging newly available cyclostome genomes. Our analysis surprisingly reveals a significantly reduced FGF repertoire in lampreys (17 genes) and hagfishes (12 genes) compared to jawed vertebrates (22–32 genes). This finding suggests extensive FGF gene loss in cyclostomes following their unique genome duplication history. Phylogenetic and synteny analyses confirm that all eight ancestral FGF subfamilies were first established in the common ancestor of vertebrates. Significantly, we report the discovery of a novel FGF gene, Fgf25 , within the FGF4/5/6/25 subfamily, uniquely retained in actinopterygians but lost in sarcopterygians. We also propose a new evolutionary model for Fgf3 , suggesting its origin via tandem duplication of an unknown Fgf gene after the 1R V but before the second genome duplication, ultimately leading to the conserved Fgf3-Fgf4-Fgf19 gene linkage in jawed vertebrates. This detailed characterization of the cyclostome FGF repertoire provides insights into early vertebrate FGF evolution and a valuable resource for future investigations into cyclostome evolution and development.