Emergent expression of fitness-conferring genes by phenotypic selection
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Published version
Author(s)
Type
Journal Article
Abstract
Genotypic and phenotypic adaptation is the consequence of ongoing natural selection in populations and is key to predicting and preventing drug resistance. Whereas classic antibiotic persistence is all-or-nothing, here we demonstrate that an antibiotic resistance gene displays linear dose-responsive selection for increased expression in proportion to rising antibiotic concentration in growing E. coli populations. Furthermore, we report the potentially wide-spread nature of this form of emergent gene expression by instantaneous phenotypic selection process under bactericidal and bacteriostatic antxibiotic treatment, as well as an amino acid synthesis pathway enzyme under a range of auxotrophic conditions. We propose an analogy to Ohm’s law in electricity (V=IR) where selection pressure acts similarly to voltage (V), gene expression to current (I), and resistance (R) to cellular machinery constraints and costs. Lastly, mathematical modelling using agent-based models of stochastic gene expression in growing populations and Bayesian model selection reveal that the emergent gene expression mechanism requires variability in gene expression within an isogenic population, and a cellular ‘memory’ from positive feedbacks between growth and expression of any fitness-conferring gene. Finally, we discuss the connection of the observed phenomenon to a previously described general fluctuation-response relationship in biology.
Date Issued
2022-07
Date Acceptance
2022-05-23
Citation
PNAS Nexus, 2022, 1 (3), pp.1-13
ISSN
2752-6542
Publisher
Oxford University Press
Start Page
1
End Page
13
Journal / Book Title
PNAS Nexus
Volume
1
Issue
3
Copyright Statement
© The Author(s) 2022. Published by Oxford University Press on behalf of National Academy of Sciences.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Wellcome Trust
Wellcome Trust
Identifier
https://academic.oup.com/pnasnexus/article/1/3/pgac069/6605288
Grant Number
102944/Z/13/Z
102944/Z/13/Z
Publication Status
Published
Date Publish Online
2022-06-10