Evolutionary fates within a microbial population highlight an essential role for protein folding during natural selection.

Molecular Systems Biology
Matthew I PeñaYousif Shamoo

Abstract

Systems biology can offer a great deal of insight into evolution by quantitatively linking complex properties such as protein structure, folding, and function to the fitness of an organism. Although the link between diseases such as Alzheimer's and misfolding is well appreciated, directly showing the importance of protein folding to success in evolution has been more difficult. We show here that predicting success during adaptation can depend critically on enzyme kinetic and folding models. We used a 'weak link' method to favor mutations to an essential, but maladapted, adenylate kinase gene within a microbial population that resulted in the identification of five mutants that arose nearly simultaneously and competed for success. Physicochemical characterization of these mutants showed that, although steady-state enzyme activity is important, success within the population is critically dependent on resistance to denaturation and aggregation. A fitness function based on in vitro measurements of enzyme activity, reversible and irreversible unfolding, and the physiological context reproduces in vivo evolutionary fates in the population linking organismal adaptation to its physical basis.

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Citations

Mar 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·Shimon BershteinEugene I Shakhnovich
Dec 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·Katarzyna WalkiewiczYousif Shamoo
Mar 23, 2012·Bioinformatics·William H MatherLev S Tsimring
Oct 25, 2011·Applied and Environmental Microbiology·Ian K BlabyEudes de Crécy
May 3, 2014·Applied Microbiology and Biotechnology·Kristen BlanchardIchiro Matsumura
Feb 16, 2013·Genetics·Jennifer LachowiecChristine Queitsch
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Jul 15, 2016·Biophysical Journal·Liskin Swint-Kruse
Aug 21, 2013·Antimicrobial Agents and Chemotherapy·Corwin MillerYousif Shamoo
Jul 19, 2013·Nature Reviews. Genetics·Michael J Harms, Joseph W Thornton
Dec 24, 2017·Molecular Systems Biology·Anisha M PerezYousif Shamoo
Sep 24, 2011·Science·Ryan L Frisch, Susan M Rosenberg
Jun 22, 2017·FEMS Microbiology Reviews·Herwig BachmannBas Teusink
Apr 10, 2019·Molecular Systems Biology·Natalia Sanchez de GrootM Madan Babu

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Methods Mentioned

BETA
PCR
differential scanning calorimetry
protein folding
protein-folding

Software Mentioned

GraphPad
Prism
Origin

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