Ancestrally Reconstructed von Willebrand Factor Reveals Evidence for Trench Warfare Coevolution between Opossums and Pit Vipers

Danielle H. Drabeck, Alexandra Rucavado, Erika Hingst-Zaher, Antony Dean, Sharon A. Jansa

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Opossums in the tribe Didelphini are resistant to pit viper venoms and are hypothesized to be coevolving with venomous snakes. Specifically, a protein involved in blood clotting (von Willebrand factor [vWF] which is targeted by snake venom C-type lectins [CTLs]) has been found to undergo rapid adaptive evolution in Didelphini. Several unique amino acid changes in vWF could explain their resistance; however, experimental evidence that these changes disrupt binding to venom CTLs was lacking. Furthermore, without explicit testing of ancestral phenotypes to reveal the mode of evolution, the assertion that this system represents an example of coevolution rather than noncoevolutionary adaptation remains unsupported. Using expressed vWF proteins and purified venom CTLs, we quantified binding affinity for vWF proteins from all resistant taxa, their venom-sensitive relatives, and their ancestors. We show that CTL-resistant vWF is present in opossums outside clade Didelphini and likely across a wider swath of opossums (family Didelphidae) than previously thought. Ancestral reconstruction and in vitro testing of vWF phenotypes in a clade of rapidly evolving opossums reveal a pattern consistent with trench warfare coevolution between opossums and their venomous snake prey.

Original languageEnglish (US)
Article numbermsac140
JournalMolecular biology and evolution
Issue number7
StatePublished - Jul 1 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.


  • ancestral-state reconstruction
  • coevolution
  • convergent evolution
  • functional synthesis
  • opossums
  • trench warfare
  • venom resistance

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural


Dive into the research topics of 'Ancestrally Reconstructed von Willebrand Factor Reveals Evidence for Trench Warfare Coevolution between Opossums and Pit Vipers'. Together they form a unique fingerprint.

Cite this