HMN 2025: How Hagfish olfactory genes hint at ancient origins of vertebrate sense of smell

The diversity of olfactory receptors in hagfish and the implications for early vertebrate evolution
Credit: Tsukuru Maeda

Researchers at University of Tsukuba and their collaborators have conducted a comprehensive analysis of the olfactory receptor repertoire of the hagfish (Eptatretus burgeri), a jawless vertebrate. This organism retains many primitive features yet possesses a highly developed olfactory system.

The researchers’ findings, published in the journal iScience, reveal that certain olfactory receptor gene families have undergone substantial lineage-specific diversification, suggesting that the vertebrate common ancestor likely possessed a broader and more complex olfactory repertoire than previously proposed.

Animals, including humans, rely on their sense of smell to locate food, avoid predators, and communicate. This sensory ability depends on specialized receptor proteins.

In vertebrates, four major receptor families mediate olfaction; these include olfactory receptors (ORs), vomeronasal type 1 receptors (V1Rs), vomeronasal type 2 receptors (V2Rs), and trace amine-associated receptors (TAARs). However, the evolutionary origin and early diversification patterns of these receptor classes remain poorly understood.

In this study, the researchers examined the hagfish genome for genes linked to ORs. In total, they identified 48 OR genes, two V1R genes, a surprisingly large set of 135 V2R genes, and no TAAR gene.

Subsequent expression analyses confirmed that most of these genes were actively expressed in the olfactory organ, indicating that they may play functional roles in smell perception. Notably, the presence of true V2Rs in hagfish overturns the long-standing assumption that these receptors evolved only in jawed vertebrates.

Conversely, the results of this study suggest that functional V2Rs were already present in the common ancestor of all vertebrates and that they subsequently diversified in a lineage-specific manner.

Overall, this discovery provides critical insight into the evolution of vertebrate olfaction and underscores the importance of hagfish as a model for reconstructing the sensory biology of early vertebrates.

More information:
Hirofumi Kariyayama et al, Hagfish olfactory repertoire illuminates lineage-specific diversification of olfaction in basal vertebrates, iScience (2025). DOI: 10.1016/j.isci.2025.114118


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