---
_id: '9410'
abstract:
- lang: eng
  text: Antibiotic concentrations vary dramatically in the body and the environment.
    Hence, understanding the dynamics of resistance evolution along antibiotic concentration
    gradients is critical for predicting and slowing the emergence and spread of resistance.
    While it has been shown that increasing the concentration of an antibiotic slows
    resistance evolution, how adaptation to one antibiotic concentration correlates
    with fitness at other points along the gradient has not received much attention.
    Here, we selected populations of Escherichia coli at several points along a concentration
    gradient for three different antibiotics, asking how rapidly resistance evolved
    and whether populations became specialized to the antibiotic concentration they
    were selected on. Populations selected at higher concentrations evolved resistance
    more slowly but exhibited equal or higher fitness across the whole gradient. Populations
    selected at lower concentrations evolved resistance rapidly, but overall fitness
    in the presence of antibiotics was lower. However, these populations readily adapted
    to higher concentrations upon subsequent selection. Our results indicate that
    resistance management strategies must account not only for the rates of resistance
    evolution but also for the fitness of evolved strains.
acknowledgement: We would like to thank Martin Ackermann, Camilo Barbosa, Nick Barton,
  Jonathan Bollback, Sebastian Bonhoeffer, Nick Colegrave, Calin Guet, Alex Hall,
  Sally Otto, Tiago Paixao, Srdjan Sarikas, Hinrich Schulenburg, Marjon de Vos and
  Michael Whitlock for insightful support.
article_number: '20200913'
article_processing_charge: No
author:
- first_name: Mato
  full_name: Lagator, Mato
  id: 345D25EC-F248-11E8-B48F-1D18A9856A87
  last_name: Lagator
- first_name: Hildegard
  full_name: Uecker, Hildegard
  id: 2DB8F68A-F248-11E8-B48F-1D18A9856A87
  last_name: Uecker
  orcid: 0000-0001-9435-2813
- first_name: Paul
  full_name: Neve, Paul
  last_name: Neve
citation:
  ama: Lagator M, Uecker H, Neve P. Adaptation at different points along antibiotic
    concentration gradients. <i>Biology letters</i>. 2021;17(5). doi:<a href="https://doi.org/10.1098/rsbl.2020.0913">10.1098/rsbl.2020.0913</a>
  apa: Lagator, M., Uecker, H., &#38; Neve, P. (2021). Adaptation at different points
    along antibiotic concentration gradients. <i>Biology Letters</i>. Royal Society
    of London. <a href="https://doi.org/10.1098/rsbl.2020.0913">https://doi.org/10.1098/rsbl.2020.0913</a>
  chicago: Lagator, Mato, Hildegard Uecker, and Paul Neve. “Adaptation at Different
    Points along Antibiotic Concentration Gradients.” <i>Biology Letters</i>. Royal
    Society of London, 2021. <a href="https://doi.org/10.1098/rsbl.2020.0913">https://doi.org/10.1098/rsbl.2020.0913</a>.
  ieee: M. Lagator, H. Uecker, and P. Neve, “Adaptation at different points along
    antibiotic concentration gradients,” <i>Biology letters</i>, vol. 17, no. 5. Royal
    Society of London, 2021.
  ista: Lagator M, Uecker H, Neve P. 2021. Adaptation at different points along antibiotic
    concentration gradients. Biology letters. 17(5), 20200913.
  mla: Lagator, Mato, et al. “Adaptation at Different Points along Antibiotic Concentration
    Gradients.” <i>Biology Letters</i>, vol. 17, no. 5, 20200913, Royal Society of
    London, 2021, doi:<a href="https://doi.org/10.1098/rsbl.2020.0913">10.1098/rsbl.2020.0913</a>.
  short: M. Lagator, H. Uecker, P. Neve, Biology Letters 17 (2021).
date_created: 2021-05-23T22:01:43Z
date_published: 2021-05-12T00:00:00Z
date_updated: 2025-05-28T11:42:50Z
day: '12'
ddc:
- '570'
department:
- _id: NiBa
doi: 10.1098/rsbl.2020.0913
ec_funded: 1
external_id:
  isi:
  - '000651501400001'
  pmid:
  - ' 33975485'
file:
- access_level: open_access
  checksum: 9c13c1f5af7609c97c741f11d293188a
  content_type: application/pdf
  creator: kschuh
  date_created: 2021-05-25T14:09:03Z
  date_updated: 2021-05-25T14:09:03Z
  file_id: '9425'
  file_name: 2021_BiologyLetters_Lagator.pdf
  file_size: 726759
  relation: main_file
  success: 1
file_date_updated: 2021-05-25T14:09:03Z
has_accepted_license: '1'
intvolume: '        17'
isi: 1
issue: '5'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B07788-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '250152'
  name: Limits to selection in biology and in evolutionary computation
publication: Biology letters
publication_identifier:
  eissn:
  - 1744957X
publication_status: published
publisher: Royal Society of London
quality_controlled: '1'
scopus_import: '1'
status: public
title: Adaptation at different points along antibiotic concentration gradients
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 17
year: '2021'
...
---
_id: '6467'
abstract:
- lang: eng
  text: Fitness interactions between mutations can influence a population’s evolution
    in many different ways. While epistatic effects are difficult to measure precisely,
    important information is captured by the mean and variance of log fitnesses for
    individuals carrying different numbers of mutations. We derive predictions for
    these quantities from a class of simple fitness landscapes, based on models of
    optimizing selection on quantitative traits. We also explore extensions to the
    models, including modular pleiotropy, variable effect sizes, mutational bias and
    maladaptation of the wild type. We illustrate our approach by reanalysing a large
    dataset of mutant effects in a yeast snoRNA (small nucleolar RNA). Though characterized
    by some large epistatic effects, these data give a good overall fit to the non-epistatic
    null model, suggesting that epistasis might have limited influence on the evolutionary
    dynamics in this system. We also show how the amount of epistasis depends on both
    the underlying fitness landscape and the distribution of mutations, and so is
    expected to vary in consistent ways between new mutations, standing variation
    and fixed mutations.
article_number: '0881'
article_processing_charge: No
article_type: original
author:
- first_name: Christelle
  full_name: Fraisse, Christelle
  id: 32DF5794-F248-11E8-B48F-1D18A9856A87
  last_name: Fraisse
  orcid: 0000-0001-8441-5075
- first_name: John J.
  full_name: Welch, John J.
  last_name: Welch
citation:
  ama: Fraisse C, Welch JJ. The distribution of epistasis on simple fitness landscapes.
    <i>Biology Letters</i>. 2019;15(4). doi:<a href="https://doi.org/10.1098/rsbl.2018.0881">10.1098/rsbl.2018.0881</a>
  apa: Fraisse, C., &#38; Welch, J. J. (2019). The distribution of epistasis on simple
    fitness landscapes. <i>Biology Letters</i>. Royal Society of London. <a href="https://doi.org/10.1098/rsbl.2018.0881">https://doi.org/10.1098/rsbl.2018.0881</a>
  chicago: Fraisse, Christelle, and John J. Welch. “The Distribution of Epistasis
    on Simple Fitness Landscapes.” <i>Biology Letters</i>. Royal Society of London,
    2019. <a href="https://doi.org/10.1098/rsbl.2018.0881">https://doi.org/10.1098/rsbl.2018.0881</a>.
  ieee: C. Fraisse and J. J. Welch, “The distribution of epistasis on simple fitness
    landscapes,” <i>Biology Letters</i>, vol. 15, no. 4. Royal Society of London,
    2019.
  ista: Fraisse C, Welch JJ. 2019. The distribution of epistasis on simple fitness
    landscapes. Biology Letters. 15(4), 0881.
  mla: Fraisse, Christelle, and John J. Welch. “The Distribution of Epistasis on Simple
    Fitness Landscapes.” <i>Biology Letters</i>, vol. 15, no. 4, 0881, Royal Society
    of London, 2019, doi:<a href="https://doi.org/10.1098/rsbl.2018.0881">10.1098/rsbl.2018.0881</a>.
  short: C. Fraisse, J.J. Welch, Biology Letters 15 (2019).
date_created: 2019-05-19T21:59:15Z
date_published: 2019-04-03T00:00:00Z
date_updated: 2023-08-25T10:34:41Z
day: '03'
department:
- _id: BeVi
- _id: NiBa
doi: 10.1098/rsbl.2018.0881
ec_funded: 1
external_id:
  isi:
  - '000465405300010'
  pmid:
  - '31014191'
intvolume: '        15'
isi: 1
issue: '4'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1098/rsbl.2018.0881
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
publication: Biology Letters
publication_identifier:
  eissn:
  - 1744957X
  issn:
  - '17449561'
publication_status: published
publisher: Royal Society of London
quality_controlled: '1'
related_material:
  link:
  - relation: supplementary_material
    url: https://dx.doi.org/10.6084/m9.figshare.c.4461008
  record:
  - id: '9798'
    relation: research_data
    status: public
  - id: '9799'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: The distribution of epistasis on simple fitness landscapes
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 15
year: '2019'
...