Evolution of weak cooperative interactions for biological specificity
Name
E11053.full.pdf
Description
Published version
Size
804.65 KB
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Unknown
Checksum (MD5)
06107467bfdcde3293ad5a624b730755
Author(s)
Gao, Ang
Shrinivas, Krishna
Lepeudry, Paul
Suzuki, Hiroshi I.
Sharp, Phillip A.
Chakraborty, Arup K.
Date Issued
November 2018
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Version
Final published version
Abstract
© 2018 National Academy of Sciences. All rights reserved. A hallmark of biological systems is that particular functions and outcomes are realized in specific contexts, such as when particular signals are received. One mechanism for mediating specificity is described by Fisher’s “lock and key” metaphor, exemplified by enzymes that bind selectively to a particular substrate via specific finely tuned interactions. Another mechanism, more prevalent in multicellular organisms, relies on multivalent weak cooperative interactions. Its importance has recently been illustrated by the recognition that liquid-liquid phase transitions underlie the formation of mem-braneless condensates that perform specific cellular functions. Based on computer simulations of an evolutionary model, we report that the latter mechanism likely became evolutionarily prominent when a large number of tasks had to be performed specifically for organisms to function properly. We find that the emergence of weak cooperative interactions for mediating specificity results in organisms that can evolve to accomplish new tasks with fewer, and likely less lethal, mutations. We argue that this makes the system more capable of undergoing evolutionary changes robustly, and thus this mechanism has been repeatedly positively selected in increasingly complex organisms. Specificity mediated by weak cooperative interactions results in some useful cross-reactivity for related tasks, but at the same time increases susceptibility to misregulation that might lead to pathologies.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Physics
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1815912115
