@article{Ciechonska:2022:pnasnexus/pgac069,
author = {Ciechonska, M and Sturrock, M and Grob, A and Larrouy-Maumus, G and Shahrezaei, V and Isalan, M},
doi = {pnasnexus/pgac069},
journal = {PNAS Nexus},
pages = {1--13},
title = {Emergent expression of fitness-conferring genes by phenotypic selection},
url = {http://dx.doi.org/10.1093/pnasnexus/pgac069},
volume = {1},
year = {2022}
}

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TY  - JOUR
AB  - 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.
AU  - Ciechonska,M
AU  - Sturrock,M
AU  - Grob,A
AU  - Larrouy-Maumus,G
AU  - Shahrezaei,V
AU  - Isalan,M
DO  - pnasnexus/pgac069
EP  - 13
PY  - 2022///
SN  - 2752-6542
SP  - 1
TI  - Emergent expression of fitness-conferring genes by phenotypic selection
T2  - PNAS Nexus
UR  - http://dx.doi.org/10.1093/pnasnexus/pgac069
UR  - https://academic.oup.com/pnasnexus/article/1/3/pgac069/6605288
UR  - http://hdl.handle.net/10044/1/97390
VL  - 1
ER  - 

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