A research group led by Assistant Professor Daichi Suzuki of the Institute of Life and Environmental Sciences at the University of Tsukuba, Hirofumi Kariyayama (a graduate student at the time of the research) of the Graduate School of Comprehensive Human Sciences at the University of Tsukuba, and Assistant Professor Yoko Yamaguchi of the Institute of Agricultural and Life Sciences, Academic Assembly at Shimane University have revealed that specific olfactory-related receptor genes in the cyclostome "hagfish" have independently increased in number. The hagfish has developed its olfactory system while retaining many characteristics of primitive vertebrates. This discovery suggests that early vertebrates may have possessed a more diverse range of olfactory-related receptors than previously thought. This finding is expected to contribute to understanding the evolution of olfaction in vertebrates, including humans. The results were published in iScience on December 19.
Provided by Suzuki from the Institute of Life and Environmental Science, University of Tsukuba
Humans rely on olfactory receptors to use our environment's odor information to search for food and to detect danger. Vertebrates, including humans, have four types of olfactory receptor proteins: ORs (olfactory receptors), V1Rs (vomeronasal type 1 receptors), V2Rs (vomeronasal type 2 receptors), and TAARs (trace amine-associated receptors). These responses are known to differ depending on the type of odor molecule. However, it is unknown when these olfactory-related receptors were acquired during vertebrate evolution and how exactly they diversified.
One reason behind this was the limited progress on research regarding olfactory-related receptors in hagfishes. Hagfishes are cyclostomes that retain many characteristics of primitive vertebrates, with well-developed olfaction. However, they can only be readily obtained in limited regions.
Therefore, the research group first examined publicly available genome information for the representative hagfish species Eptatretus burgeri to determine which olfactory-related receptors existed and how many of them there are.
They found 48 ORs, 2 V1Rs, and as many as 135 V2R genes in hagfish. There were no TAARs.
Molecular phylogenetic analysis revealed that ORs and V2Rs diversified independently in the hagfish lineage. When examining the genomic distribution of the remarkably numerous V2Rs, the researchers found that many exist at high density in specific regions, with phylogenetically related V2Rs also located in close proximity on the genome. It was suggested that V2Rs may have increased in number through repeated local duplications.
Next, the research group examined gene expression of these olfactory-related receptors. This was carried out to verify whether the olfactory-related receptors identified are actually involved in odor substance reception.
Transcriptome analysis was performed based on total RNA extracted from various hagfish tissues, including the olfactory organ, brain, and liver.
The results showed that almost all of the identified olfactory-related receptor genes tended to be expressed relatively strongly in the olfactory organ. Furthermore, the researchers confirmed that the OR, V1R, and V2R olfactory-related receptor genes identified were expressed in olfactory sensory neurons that receive odors. These findings demonstrated that the identified genes are true olfactory-related receptor genes responsible for olfaction.
Until now, it was thought that cyclostomes lack true V2Rs that function as olfactory receptors, and therefore that the common ancestor of vertebrates did not possess true V2Rs. However, this study suggests the possibility that true V2Rs already existed at the common ancestor stage.
In the future, the group plans to examine interspecific diversity within hagfishes, physiological responses of hagfish to odor substances, and olfactory behavior.
Suzuki commented: "Many aspects of the olfactory information processing mechanism and evolutionary origin remain unexplained. Using this research as a starting point, I hope to advance research that deepens our understanding of the olfactory systems not only of hagfish but of vertebrates in general. I also hope this can serve as a foothold for elucidating the ecology of hagfish as 'ocean scavengers' that feed on the carcasses of whales and other animals, potentially leading to marine environmental conservation."
Journal Information
Publication: iScience
Title: Hagfish olfactory repertoire illuminates lineage-specific diversification of olfaction in basal vertebrates
DOI: 10.1016/j.isci.2025.114118
This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.