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Domain loss enabled evolution of novel functions in the snake three-finger toxin gene superfamily
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 extens...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421932/ https://www.ncbi.nlm.nih.gov/pubmed/37567881 http://dx.doi.org/10.1038/s41467-023-40550-0 |
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author | Koludarov, Ivan Senoner, Tobias Jackson, Timothy N. W. Dashevsky, Daniel Heinzinger, Michael Aird, Steven D. Rost, Burkhard |
author_facet | Koludarov, Ivan Senoner, Tobias Jackson, Timothy N. W. Dashevsky, Daniel Heinzinger, Michael Aird, Steven D. Rost, Burkhard |
author_sort | Koludarov, Ivan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10421932 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104219322023-08-13 Domain loss enabled evolution of novel functions in the snake three-finger toxin gene superfamily Koludarov, Ivan Senoner, Tobias Jackson, Timothy N. W. Dashevsky, Daniel Heinzinger, Michael Aird, Steven D. Rost, Burkhard Nat Commun Article 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. Nature Publishing Group UK 2023-08-11 /pmc/articles/PMC10421932/ /pubmed/37567881 http://dx.doi.org/10.1038/s41467-023-40550-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Koludarov, Ivan Senoner, Tobias Jackson, Timothy N. W. Dashevsky, Daniel Heinzinger, Michael Aird, Steven D. Rost, Burkhard Domain loss enabled evolution of novel functions in the snake three-finger toxin gene superfamily |
title | Domain loss enabled evolution of novel functions in the snake three-finger toxin gene superfamily |
title_full | Domain loss enabled evolution of novel functions in the snake three-finger toxin gene superfamily |
title_fullStr | Domain loss enabled evolution of novel functions in the snake three-finger toxin gene superfamily |
title_full_unstemmed | Domain loss enabled evolution of novel functions in the snake three-finger toxin gene superfamily |
title_short | Domain loss enabled evolution of novel functions in the snake three-finger toxin gene superfamily |
title_sort | domain loss enabled evolution of novel functions in the snake three-finger toxin gene superfamily |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421932/ https://www.ncbi.nlm.nih.gov/pubmed/37567881 http://dx.doi.org/10.1038/s41467-023-40550-0 |
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