Molding the business end of neurotoxins by diversifying evolution

Adi Kozminsky-Atias, Noam Zilberberg

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

A diverse range of organisms utilize neurotoxins that target specific ion channels and modulate their activity. Typically, toxins are clustered into several multigene families, providing an organism with the upper hand in the never-ending predator-prey arms race. Several gene families, including those encoding certain neurotoxins, have been subject to diversifying selection forces, resulting in rapid gene evolution. Here we sought a spatial pattern in the distribution of both diversifying and purifying selection forces common to neurotoxin gene families. Utilizing the mechanistic empirical combination model, we analyzed various toxin families from different phyla affecting various receptors and relying on diverse modes of action. Through this approach, we were able to detect clear correlations between the pharmacological surface of a toxin and rapidly evolving domains, rich in positively selected residues. On the other hand, patches of negatively selected residues were restricted to the nontoxic face of the molecule and most likely help in stabilizing the tertiary structure of the toxin. We thus propose a mutual evolutionary strategy of venomous animals in which adaptive molecular evolution is directed toward the toxin active surface. Furthermore, we propose that the binding domains of unstudied toxins could be readily predicted using evolutionary considerations.

Original languageEnglish
Pages (from-to)576-586
Number of pages11
JournalFASEB Journal
Volume26
Issue number2
DOIs
StatePublished - 1 Feb 2012

Keywords

  • Active surface
  • Ion channels
  • Multigene families

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint

Dive into the research topics of 'Molding the business end of neurotoxins by diversifying evolution'. Together they form a unique fingerprint.

Cite this