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dc.contributor.authorTsend-Ayush, E
dc.contributor.authorHe, C
dc.contributor.authorMyers, MA
dc.contributor.authorAndrikopoulos, S
dc.contributor.authorWong, N
dc.contributor.authorSexton, PM
dc.contributor.authorWootten, D
dc.contributor.authorForbes, BE
dc.contributor.authorGrutzner, F
dc.date.accessioned2020-12-21T03:48:08Z
dc.date.available2020-12-21T03:48:08Z
dc.date.issued2016-11-29
dc.identifierpii: srep37744
dc.identifier.citationTsend-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.
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/11343/257358
dc.description.abstractThe 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.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleMonotreme glucagon-like peptide-1 in venom and gut: one gene - two very different functions
dc.typeJournal Article
dc.identifier.doi10.1038/srep37744
melbourne.affiliation.departmentMedicine (Austin & Northern Health)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleScientific Reports
melbourne.source.volume6
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1121114
melbourne.contributor.authorAndrikopoulos, Sofianos
melbourne.contributor.authorWONG, NICOLE
dc.identifier.eissn2045-2322
melbourne.accessrightsOpen Access


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