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.—Kozminsky-Atias, A., Zilberberg, N. Molding the business end of neurotoxins by diversifying evolution. active surface ion channels multigene families Footnotes This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information. Received June 9, 2011. Accepted October 6, 2011. © FASEB Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? « Previous | Next Article » Table of Contents This Article Published online before print October 18, 2011 , doi: 10.1096/fj.11-187179 February 2012 The FASEB Journal vol. 26 no. 2 576-586 » Abstract Full Text Full Text (PDF) Supplemental Data All Versions of this Article: fj.11-187179v1 26/2/576 most recent Classifications Research Communications Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Kozminsky-Atias, A. Articles by Zilberberg, N. PubMed PubMed citation Articles by Kozminsky-Atias, A. Articles by Zilberberg, N. Related Content Load related web page information Sharing Email this article to a colleague Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? Current Issue February 2012, 26 (2) Alert me to new issues of The FASEB Journal Submit Manuscripts Online Press Room Information for Authors Information for Reviewers Editorial Board Editorial Policies Subscriptions Librarian's Resource Activate Online View Collected Papers Breakthroughs in Bioscience Advertising Copyright Permissions Feedback Subscribe to RSS FASEB Publication Services Go to FASEB Online Copyright © 2012 by the Federation of American Societies for Experimental Biology Print ISSN: 0892-6638 Online ISSN: 1530-6860 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-23107677-1"); pageTracker._trackPageview();

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