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Multiple mutations in the Nav1.4 sodium channel of New Guinean toxic birds provide autoresistance to deadly batrachotoxin
Natural History Museum of Denmark University of Copenhagen Copenhagen Denmark.ORCID iD: 0000-0002-6095-9059
Natural History Museum of Denmark University of Copenhagen Copenhagen Denmark.
Chemical Biology of Microbe–Host Interactions Leibniz Institute for Natural Product Research and Infection Biology e. V., Hans‐Knöll‐Institute Jena Germany.
Chemical Biology of Microbe–Host Interactions Leibniz Institute for Natural Product Research and Infection Biology e. V., Hans‐Knöll‐Institute Jena Germany;Institute for Pharmaceutical Microbiology, University of Bonn Bonn Germany.
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2024 (English)In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 33, p. 1-14Article in journal, News item (Refereed) Published
Abstract [en]

Toxicity has evolved multiple times across the tree of life and serves important func-tions related to hunting, defence and parasite deterrence. Toxins are produced either insitu by the toxic organism itself or associated symbionts, or acquired through diet. Theability to exploit toxins from external sources requires adaptations that prevent toxiceffects on the consumer (autoresistance). Here, we examine genomic adaptations thatcould facilitate autoresistance to the diet-acquired potent neurotoxic alkaloid batra-chotoxin (BTX) in New Guinean toxic birds. Our work documents two new toxic birdspecies and shows that toxic birds carry multiple mutations in the SCN4A gene thatare under positive selection. This gene encodes the most common vertebrate muscleNav channel (Nav1.4). Molecular docking results indicate that some of the mutationsthat are present in the pore-forming segment of the Nav channel, where BTX binds,could reduce its binding affinity. These mutations should therefore prevent the con-tinuous opening of the sodium channels that BTX binding elicits, thereby preventingmuscle paralysis and ultimately death. Although these mutations are different fromthose present in Neotropical Phyllobates poison dart frogs, they occur in the samesegments of the Nav1.4 channel. Consequently, in addition to uncovering a greater diversity of toxic bird species than previously known, our work provides an intriguingexample of molecular-level convergent adaptations allowing frogs and birds to ingestand use the same neurotoxin. This suggests that genetically modified Nav1.4 chan-nels represent a key adaptation to BTX tolerance and exploitation across vertebrates.

Place, publisher, year, edition, pages
2024. Vol. 33, p. 1-14
Keywords [en]
Ifrita, neurotoxins, Pachycephalidae, Pitohui, voltage-gated sodium channels
National Category
Natural Sciences
Research subject
Diversity of life
Identifiers
URN: urn:nbn:se:nrm:diva-5738DOI: 10.1111/mec.16878OAI: oai:DiVA.org:nrm-5738DiVA, id: diva2:1918050
Funder
German Research Foundation (DFG), 239748522 ‐ CRC1127Available from: 2024-12-04 Created: 2024-12-04 Last updated: 2025-09-12Bibliographically approved

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Bodawatta, Kasun H.Beemelmanns, ChristinePoulsen, MichaelJønsson, Knud A.
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