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Domain loss enabled evolution of novel functions in the snake three-finger toxin gene superfamily

Author

Listed:
  • Ivan Koludarov

    (TUM (Technical University of Munich) Department of Informatics, Bioinformatics & Computational Biology—i12)

  • Tobias Senoner

    (TUM (Technical University of Munich) Department of Informatics, Bioinformatics & Computational Biology—i12)

  • Timothy N. W. Jackson

    (University of Melbourne)

  • Daniel Dashevsky

    (Commonwealth Scientific & Industrial Research Organisation)

  • Michael Heinzinger

    (TUM (Technical University of Munich) Department of Informatics, Bioinformatics & Computational Biology—i12)

  • Steven D. Aird

    (7744-23 Hotaka Ariake)

  • Burkhard Rost

    (TUM (Technical University of Munich) Department of Informatics, Bioinformatics & Computational Biology—i12
    Institute for Advanced Study (TUM-IAS)
    TUM School of Life Sciences Weihenstephan (WZW))

Abstract

Three-finger toxins (3FTXs) are a functionally diverse family of toxins, apparently unique to venoms of caenophidian snakes. Although the ancestral function of 3FTXs is antagonism of nicotinic acetylcholine receptors, redundancy conferred by the accumulation of duplicate genes has facilitated extensive neofunctionalization, such that derived members of the family interact with a range of targets. 3FTXs are members of the LY6/UPAR family, but their non-toxin ancestor remains unknown. Combining traditional phylogenetic approaches, manual synteny analysis, and machine learning techniques (including AlphaFold2 and ProtT5), we have reconstructed a detailed evolutionary history of 3FTXs. We identify their immediate ancestor as a non-secretory LY6, unique to squamate reptiles, and propose that changes in molecular ecology resulting from loss of a membrane-anchoring domain and changes in gene expression, paved the way for the evolution of one of the most important families of snake toxins.

Suggested Citation

  • Ivan Koludarov & Tobias Senoner & Timothy N. W. Jackson & Daniel Dashevsky & Michael Heinzinger & Steven D. Aird & Burkhard Rost, 2023. "Domain loss enabled evolution of novel functions in the snake three-finger toxin gene superfamily," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40550-0
    DOI: 10.1038/s41467-023-40550-0
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    References listed on IDEAS

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    3. Nicholas R. Casewell & Gavin A. Huttley & Wolfgang Wüster, 2012. "Dynamic evolution of venom proteins in squamate reptiles," Nature Communications, Nature, vol. 3(1), pages 1-10, January.
    4. Martin Steinegger & Johannes Söding, 2018. "Clustering huge protein sequence sets in linear time," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
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