Universität zu Köln

Salverda, Merijn L. M., Koomen, Jeroen, Koopmanschap, Bertha, Zwart, Mark P. and de Vissera, J. Arjan G. M. (2017). Adaptive benefits from small mutation supplies in an antibiotic resistance enzyme. Proc. Natl. Acad. Sci. U. S. A., 114 (48). S. 12773 - 12779. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

Populations with large mutation supplies adapt via the greedy substitution of the fittest genotype available, leading to fast and repeatable short-term responses. At longer time scales, smaller mutation supplies may in theory lead to larger improvements when distant high-fitness genotypes more readily evolve from lower-fitness intermediates. Here we test for long-term adaptive benefits from small mutation supplies using in vitro evolution of an antibiotic-degrading enzyme in the presence of a novel antibiotic. Consistent with predictions, large mutant libraries cause rapid initial adaptation via the substitution of cohorts of mutations, but show later deceleration and convergence. Smaller libraries show on average smaller initial, but also more variable, improvements, with two lines yielding alleles with exceptionally high resistance levels. These two alleles share three mutations with the large-library alleles, which are known from previous work, but also have unique mutations. Replay evolution experiments and analyses of the adaptive landscape of the enzyme suggest that the benefit resulted from a combination of avoiding mutational cohorts leading to local peaks and chance. Our results demonstrate adaptive benefits from limited mutation supplies on a rugged fitness landscape, which has implications for artificial selection protocols in biotechnology and argues for a better understanding of mutation supplies in clinical settings.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Salverda, Merijn L. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koomen, Jeroen UNSPECIFIED UNSPECIFIED UNSPECIFIED Koopmanschap, Bertha UNSPECIFIED UNSPECIFIED UNSPECIFIED Zwart, Mark P. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Vissera, J. Arjan G. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-210888
DOI:	10.1073/pnas.1712999114
Journal or Publication Title:	Proc. Natl. Acad. Sci. U. S. A.
Volume:	114
Number:	48
Page Range:	S. 12773 - 12779
Date:	2017
Publisher:	NATL ACAD SCIENCES
Place of Publication:	WASHINGTON
ISSN:	0027-8424
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TEM-1 BETA-LACTAMASE; PROTEIN EVOLUTION; ASEXUAL POPULATIONS; NATURAL EVOLUTION; ESCHERICHIA-COLI; FITNESS; PREDICTABILITY; EPISTASIS; SELECTION; TRAJECTORIES Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21088