Monotreme glucagon-like peptide-1 in venom and gut: one gene - two very different functions
AuthorTsend-Ayush, E; He, C; Myers, MA; Andrikopoulos, S; Wong, N; Sexton, PM; Wootten, D; Forbes, BE; Grutzner, F
Source TitleScientific Reports
PublisherNATURE PUBLISHING GROUP
AffiliationMedicine and Radiology
Document TypeJournal Article
CitationsTsend-Ayush, E., He, C., Myers, M. A., Andrikopoulos, S., Wong, N., Sexton, P. M., Wootten, D., Forbes, B. E. & Grutzner, F. (2016). Monotreme glucagon-like peptide-1 in venom and gut: one gene - two very different functions. SCIENTIFIC REPORTS, 6 (1), https://doi.org/10.1038/srep37744.
Access StatusOpen Access
The importance of Glucagon like peptide 1 (GLP-1) for metabolic control and insulin release sparked the evolution of genes mimicking GLP-1 action in venomous species (e.g. Exendin-4 in Heloderma suspectum (gila monster)). We discovered that platypus and echidna express a single GLP-1 peptide in both intestine and venom. Specific changes in GLP-1 of monotreme mammals result in resistance to DPP-4 cleavage which is also observed in the GLP-1 like Exendin-4 expressed in Heloderma venom. Remarkably we discovered that monotremes evolved an alternative mechanism to degrade GLP-1. We also show that monotreme GLP-1 stimulates insulin release in cultured rodent islets, but surprisingly shows low receptor affinity and bias toward Erk signaling. We propose that these changes in monotreme GLP-1 are the result of conflicting function of this peptide in metabolic control and venom. This evolutionary path is fundamentally different from the generally accepted idea that conflicting functions in a single gene favour duplication and diversification, as is the case for Exendin-4 in gila monster. This provides novel insight into the remarkably different metabolic control mechanism and venom function in monotremes and an unique example of how different selective pressures act upon a single gene in the absence of gene duplication.
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