Universität zu Köln

van Dijk, Thomas ORCID: 0000-0001-9063-4338, Hwang, Sungmin, Krug, Joachim ORCID: 0000-0002-2143-6490, de Visser, J. Arjan G. M. and Zwart, Mark P. (2017). Mutation supply and the repeatability of selection for antibiotic resistance. Phys. Biol., 14 (5). BRISTOL: IOP PUBLISHING LTD. ISSN 1478-3975

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Abstract

Whether evolution can be predicted is a key question in evolutionary biology. Here we set out to better understand the repeatability of evolution, which is a necessary condition for predictability. We explored experimentally the effect of mutation supply and the strength of selective pressure on the repeatability of selection from standing genetic variation. Different sizes of mutant libraries of antibiotic resistance gene TEM-1 beta-lactamase in Escherichia coli, generated by error-prone PCR, were subjected to different antibiotic concentrations. We determined whether populations went extinct or survived, and sequenced the TEM gene of the surviving populations. The distribution of mutations per allele in our mutant libraries followed a Poisson distribution. Extinction patterns could be explained by a simple stochastic model that assumed the sampling of beneficial mutations was key for survival. In most surviving populations, alleles containing at least one known large-effect beneficial mutation were present. These genotype data also support a model which only invokes sampling effects to describe the occurrence of alleles containing large-effect driver mutations. Hence, evolution is largely predictable given cursory knowledge of mutational fitness effects, the mutation rate and population size. There were no clear trends in the repeatability of selected mutants when we considered all mutations present. However, when only known large-effect mutations were considered, the outcome of selection is less repeatable for large libraries, in contrast to expectations. We show experimentally that alleles carrying multiple mutations selected from large libraries confer higher resistance levels relative to alleles with only a known large-effect mutation, suggesting that the scarcity of high-resistance alleles carrying multiple mutations may contribute to the decrease in repeatability at large library sizes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code van Dijk, Thomas UNSPECIFIED orcid.org/0000-0001-9063-4338 UNSPECIFIED Hwang, Sungmin UNSPECIFIED UNSPECIFIED UNSPECIFIED Krug, Joachim UNSPECIFIED orcid.org/0000-0002-2143-6490 UNSPECIFIED de Visser, J. Arjan G. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zwart, Mark P. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-217273
DOI:	10.1088/1478-3975/aa7f36
Journal or Publication Title:	Phys. Biol.
Volume:	14
Number:	5
Date:	2017
Publisher:	IOP PUBLISHING LTD
Place of Publication:	BRISTOL
ISSN:	1478-3975
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Physics > Institut für Biologische Physik
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TEM-1 BETA-LACTAMASE; BENEFICIAL MUTATIONS; FITNESS LANDSCAPES; NATURAL EVOLUTION; EPISTASIS; POPULATION; MODEL; CONVERGENCE; ADAPTATION; PROTEINS Multiple languages Biochemistry & Molecular Biology; Biophysics Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21727