RT Journal Article
T1 Divergence of Leptin Receptor and Interleukin-6 Receptor Subunit b in Early Vertebrate Evolution and Physiological Insights from the Sea Lamprey
A1 Gong, Ningping
A1 Barany Ruiz, André
A1 Norstog, Jessica L.
A1 Larhammar, Dan
A1 Björnsson, Björn Thrandur
A1 Regish, Amy M.
A1 McCormick, Stephen D.
A1 Sheridan, Mark A.
AB Current knowledge of class-I cytokine receptors comes primarily from studies in jawed vertebrates (gnathostomes), and their origin and evolution remain unresolved. In this study, we identified a leptin receptor-like sequence (LepRL) and three interleukin-6 receptor subunit b-like sequences (IL6RBL) from a jawless vertebrate (cyclostome), the sea lamprey (Petromyzon marinus). Based on structural, phylogenetic, and syntenic analyses, we deduced that these lamprey receptors are likely distinct ohnologs to gnathostome LepR and IL6RB-related receptors, respectively, that arose in the two rounds of vertebrate whole-genome duplication (1R and 2R). Notably, lamprey LepRL likely originated from a different 1R progenitor than the one giving rise to gnathostome LepR during cyclostome hexaploidization. Differential patterns in mRNA expression of LepRL and IL6RBLs were observed among adult tissues, during larval metamorphosis, and in response to juvenile feeding. Feeding stimulated hepatic expression of LepRL and IL6RBL (namely, IL6RBL1) mRNAs in correlation with upregulation of insulin-like growth factor mRNA, whereas brain LepRL and IL6RBL1 mRNA expression was correlated positively with neuropeptide Y but inversely with intestinal content in fed juveniles. Notably, these observations along with immunolocalization of LepRL in the hypothalamus suggest a role of leptin signaling in regulating energy balance that is conserved among vertebrates. Additionally, seawater exposure stimulated branchial LepRL expression coincident with increased expression of ion transporters in ionocytes, indicating a role of leptin signaling in osmoregulation. These findings provide new insight into the early evolution of class-I cytokine receptors and reveal diverse functions of the leptin signaling system in jawless vertebrate.
PB Oxford University Press
SN 0737-4038
YR 2025
FD 2025-07-01
LK https://hdl.handle.net/20.500.14352/123560
UL https://hdl.handle.net/20.500.14352/123560
LA eng
NO Gong, N., Barany, A., Norstog, J. L., Larhammar, D., Björnsson, B. T., Regish, A. M., McCormick, S. D., & Sheridan, M. A. (2025). Divergence of Leptin Receptor and Interleukin-6 Receptor Subunit b in Early Vertebrate Evolution and Physiological Insights from the Sea Lamprey. Molecular Biology and Evolution, 42(7). https://doi.org/10.1093/MOLBEV/MSAF157
NO This work was supported by the U.S. National Science Foundation (NSF grant 1558037 to M.A.S. and S.D.M.) and the Swedish Research Council for Sustainable Development (FORMAS grant 2015-00724 to B.Th.B.).
NO National Science Foundation (USA)
NO Swedish Research Council for Sustainable Development
DS Docta Complutense
RD 7 sept 2025