---
_id: '1571'
abstract:
- lang: eng
text: Epistatic interactions can frustrate and shape evolutionary change. Indeed,
phenotypes may fail to evolve when essential mutations are only accessible through
positive selection if they are fixed simultaneously. How environmental variability
affects such constraints is poorly understood. Here, we studied genetic constraints
in fixed and fluctuating environments using the Escherichia coli lac operon as
a model system for genotype-environment interactions. We found that, in different
fixed environments, all trajectories that were reconstructed by applying point
mutations within the transcription factor-operator interface became trapped at
suboptima, where no additional improvements were possible. Paradoxically, repeated
switching between these same environments allows unconstrained adaptation by continuous
improvements. This evolutionary mode is explained by pervasive cross-environmental
tradeoffs that reposition the peaks in such a way that trapped genotypes can repeatedly
climb ascending slopes and hence, escape adaptive stasis. Using a Markov approach,
we developed a mathematical framework to quantify the landscape-crossing rates
and show that this ratchet-like adaptive mechanism is robust in a wide spectrum
of fluctuating environments. Overall, this study shows that genetic constraints
can be overcome by environmental change and that crossenvironmental tradeoffs
do not necessarily impede but also, can facilitate adaptive evolution. Because
tradeoffs and environmental variability are ubiquitous in nature, we speculate
this evolutionary mode to be of general relevance.
acknowledgement: This work is part of the research program of the Foundation for Fundamental
Research on Matter, which is part of the Netherlands Organization for Scientific
Research (NWO). M.G.J.d.V. was (partially) funded by NWO Earth and Life Sciences
(ALW), project 863.14.015. We thank D. M. Weinreich, J. A. G. M. de Visser, T. Paixão,
J. Polechová, T. Friedlander, and A. E. Mayo for reading and commenting on earlier
versions of the manuscript and B. Houchmandzadeh, O. Rivoire, and M. Hemery for
discussions and suggestions on the Markov computation. Furthermore, we thank F.
J. Poelwijk for sharing plasmid pCascade5 and pRD007 and Y. Yokobayashi for sharing
plasmid pINV-110. We also thank the anonymous reviewers for remarks on the initial
version of the manuscript.
author:
- first_name: Marjon
full_name: De Vos, Marjon
id: 3111FFAC-F248-11E8-B48F-1D18A9856A87
last_name: De Vos
- first_name: Alexandre
full_name: Dawid, Alexandre
last_name: Dawid
- first_name: Vanda
full_name: Šunderlíková, Vanda
last_name: Šunderlíková
- first_name: Sander
full_name: Tans, Sander
last_name: Tans
citation:
ama: de Vos M, Dawid A, Šunderlíková V, Tans S. Breaking evolutionary constraint
with a tradeoff ratchet. PNAS. 2015;112(48):14906-14911. doi:10.1073/pnas.1510282112
apa: de Vos, M., Dawid, A., Šunderlíková, V., & Tans, S. (2015). Breaking evolutionary
constraint with a tradeoff ratchet. PNAS. National Academy of Sciences.
https://doi.org/10.1073/pnas.1510282112
chicago: Vos, Marjon de, Alexandre Dawid, Vanda Šunderlíková, and Sander Tans. “Breaking
Evolutionary Constraint with a Tradeoff Ratchet.” PNAS. National Academy
of Sciences, 2015. https://doi.org/10.1073/pnas.1510282112.
ieee: M. de Vos, A. Dawid, V. Šunderlíková, and S. Tans, “Breaking evolutionary
constraint with a tradeoff ratchet,” PNAS, vol. 112, no. 48. National Academy
of Sciences, pp. 14906–14911, 2015.
ista: de Vos M, Dawid A, Šunderlíková V, Tans S. 2015. Breaking evolutionary constraint
with a tradeoff ratchet. PNAS. 112(48), 14906–14911.
mla: de Vos, Marjon, et al. “Breaking Evolutionary Constraint with a Tradeoff Ratchet.”
PNAS, vol. 112, no. 48, National Academy of Sciences, 2015, pp. 14906–11,
doi:10.1073/pnas.1510282112.
short: M. de Vos, A. Dawid, V. Šunderlíková, S. Tans, PNAS 112 (2015) 14906–14911.
date_created: 2018-12-11T11:52:47Z
date_published: 2015-12-01T00:00:00Z
date_updated: 2021-01-12T06:51:40Z
day: '01'
department:
- _id: ToBo
doi: 10.1073/pnas.1510282112
intvolume: ' 112'
issue: '48'
language:
- iso: eng
month: '12'
oa_version: None
page: 14906 - 14911
publication: PNAS
publication_status: published
publisher: National Academy of Sciences
publist_id: '5600'
quality_controlled: '1'
scopus_import: 1
status: public
title: Breaking evolutionary constraint with a tradeoff ratchet
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 112
year: '2015'
...
---
_id: '1581'
abstract:
- lang: eng
text: In animal embryos, morphogen gradients determine tissue patterning and morphogenesis.
Shyer et al. provide evidence that, during vertebrate gut formation, tissue folding
generates graded activity of signals required for subsequent steps of gut growth
and differentiation, thereby revealing an intriguing link between tissue morphogenesis
and morphogen gradient formation.
article_processing_charge: No
author:
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
citation:
ama: Bollenbach MT, Heisenberg C-PJ. Gradients are shaping up. Cell. 2015;161(3):431-432.
doi:10.1016/j.cell.2015.04.009
apa: Bollenbach, M. T., & Heisenberg, C.-P. J. (2015). Gradients are shaping
up. Cell. Cell Press. https://doi.org/10.1016/j.cell.2015.04.009
chicago: Bollenbach, Mark Tobias, and Carl-Philipp J Heisenberg. “Gradients Are
Shaping Up.” Cell. Cell Press, 2015. https://doi.org/10.1016/j.cell.2015.04.009.
ieee: M. T. Bollenbach and C.-P. J. Heisenberg, “Gradients are shaping up,” Cell,
vol. 161, no. 3. Cell Press, pp. 431–432, 2015.
ista: Bollenbach MT, Heisenberg C-PJ. 2015. Gradients are shaping up. Cell. 161(3),
431–432.
mla: Bollenbach, Mark Tobias, and Carl-Philipp J. Heisenberg. “Gradients Are Shaping
Up.” Cell, vol. 161, no. 3, Cell Press, 2015, pp. 431–32, doi:10.1016/j.cell.2015.04.009.
short: M.T. Bollenbach, C.-P.J. Heisenberg, Cell 161 (2015) 431–432.
date_created: 2018-12-11T11:52:50Z
date_published: 2015-04-23T00:00:00Z
date_updated: 2022-08-25T13:56:10Z
day: '23'
department:
- _id: ToBo
- _id: CaHe
doi: 10.1016/j.cell.2015.04.009
intvolume: ' 161'
issue: '3'
language:
- iso: eng
month: '04'
oa_version: None
page: 431 - 432
publication: Cell
publication_status: published
publisher: Cell Press
publist_id: '5590'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Gradients are shaping up
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 161
year: '2015'
...
---
_id: '1586'
abstract:
- lang: eng
text: Through metabolic engineering cyanobacteria can be employed in biotechnology.
Combining the capacity for oxygenic photosynthesis and carbon fixation with an
engineered metabolic pathway allows carbon-based product formation from CO2, light,
and water directly. Such cyanobacterial 'cell factories' are constructed to produce
biofuels, bioplastics, and commodity chemicals. Efforts of metabolic engineers
and synthetic biologists allow the modification of the intermediary metabolism
at various branching points, expanding the product range. The new biosynthesis
routes 'tap' the metabolism ever more efficiently, particularly through the engineering
of driving forces and utilization of cofactors generated during the light reactions
of photosynthesis, resulting in higher product titers. High rates of carbon rechanneling
ultimately allow an almost-complete allocation of fixed carbon to product above
biomass.
author:
- first_name: Andreas
full_name: Angermayr, Andreas
id: 4677C796-F248-11E8-B48F-1D18A9856A87
last_name: Angermayr
orcid: 0000-0001-8619-2223
- first_name: Aleix
full_name: Gorchs, Aleix
last_name: Gorchs
- first_name: Klaas
full_name: Hellingwerf, Klaas
last_name: Hellingwerf
citation:
ama: Angermayr A, Gorchs A, Hellingwerf K. Metabolic engineering of cyanobacteria
for the synthesis of commodity products. Trends in Biotechnology. 2015;33(6):352-361.
doi:10.1016/j.tibtech.2015.03.009
apa: Angermayr, A., Gorchs, A., & Hellingwerf, K. (2015). Metabolic engineering
of cyanobacteria for the synthesis of commodity products. Trends in Biotechnology.
Elsevier. https://doi.org/10.1016/j.tibtech.2015.03.009
chicago: Angermayr, Andreas, Aleix Gorchs, and Klaas Hellingwerf. “Metabolic Engineering
of Cyanobacteria for the Synthesis of Commodity Products.” Trends in Biotechnology.
Elsevier, 2015. https://doi.org/10.1016/j.tibtech.2015.03.009.
ieee: A. Angermayr, A. Gorchs, and K. Hellingwerf, “Metabolic engineering of cyanobacteria
for the synthesis of commodity products,” Trends in Biotechnology, vol.
33, no. 6. Elsevier, pp. 352–361, 2015.
ista: Angermayr A, Gorchs A, Hellingwerf K. 2015. Metabolic engineering of cyanobacteria
for the synthesis of commodity products. Trends in Biotechnology. 33(6), 352–361.
mla: Angermayr, Andreas, et al. “Metabolic Engineering of Cyanobacteria for the
Synthesis of Commodity Products.” Trends in Biotechnology, vol. 33, no.
6, Elsevier, 2015, pp. 352–61, doi:10.1016/j.tibtech.2015.03.009.
short: A. Angermayr, A. Gorchs, K. Hellingwerf, Trends in Biotechnology 33 (2015)
352–361.
date_created: 2018-12-11T11:52:52Z
date_published: 2015-06-01T00:00:00Z
date_updated: 2021-01-12T06:51:46Z
day: '01'
department:
- _id: ToBo
doi: 10.1016/j.tibtech.2015.03.009
intvolume: ' 33'
issue: '6'
language:
- iso: eng
month: '06'
oa_version: None
page: 352 - 361
publication: Trends in Biotechnology
publication_status: published
publisher: Elsevier
publist_id: '5585'
quality_controlled: '1'
scopus_import: 1
status: public
title: Metabolic engineering of cyanobacteria for the synthesis of commodity products
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 33
year: '2015'
...
---
_id: '1623'
abstract:
- lang: eng
text: "Background\r\nPhotosynthetic cyanobacteria are attractive for a range of
biotechnological applications including biofuel production. However, due to slow
growth, screening of mutant libraries using microtiter plates is not feasible.\r\nResults\r\nWe
present a method for high-throughput, single-cell analysis and sorting of genetically
engineered l-lactate-producing strains of Synechocystis sp. PCC6803. A microfluidic
device is used to encapsulate single cells in picoliter droplets, assay the droplets
for l-lactate production, and sort strains with high productivity. We demonstrate
the separation of low- and high-producing reference strains, as well as enrichment
of a more productive l-lactate-synthesizing population after UV-induced mutagenesis.
The droplet platform also revealed population heterogeneity in photosynthetic
growth and lactate production, as well as the presence of metabolically stalled
cells.\r\nConclusions\r\nThe workflow will facilitate metabolic engineering and
directed evolution studies and will be useful in studies of cyanobacteria biochemistry
and physiology.\r\n"
article_number: '193'
author:
- first_name: Petter
full_name: Hammar, Petter
last_name: Hammar
- first_name: Andreas
full_name: Angermayr, Andreas
id: 4677C796-F248-11E8-B48F-1D18A9856A87
last_name: Angermayr
orcid: 0000-0001-8619-2223
- first_name: Staffan
full_name: Sjostrom, Staffan
last_name: Sjostrom
- first_name: Josefin
full_name: Van Der Meer, Josefin
last_name: Van Der Meer
- first_name: Klaas
full_name: Hellingwerf, Klaas
last_name: Hellingwerf
- first_name: Elton
full_name: Hudson, Elton
last_name: Hudson
- first_name: Hakaan
full_name: Joensson, Hakaan
last_name: Joensson
citation:
ama: Hammar P, Angermayr A, Sjostrom S, et al. Single-cell screening of photosynthetic
growth and lactate production by cyanobacteria. Biotechnology for Biofuels.
2015;8(1). doi:10.1186/s13068-015-0380-2
apa: Hammar, P., Angermayr, A., Sjostrom, S., Van Der Meer, J., Hellingwerf, K.,
Hudson, E., & Joensson, H. (2015). Single-cell screening of photosynthetic
growth and lactate production by cyanobacteria. Biotechnology for Biofuels.
BioMed Central. https://doi.org/10.1186/s13068-015-0380-2
chicago: Hammar, Petter, Andreas Angermayr, Staffan Sjostrom, Josefin Van Der Meer,
Klaas Hellingwerf, Elton Hudson, and Hakaan Joensson. “Single-Cell Screening of
Photosynthetic Growth and Lactate Production by Cyanobacteria.” Biotechnology
for Biofuels. BioMed Central, 2015. https://doi.org/10.1186/s13068-015-0380-2.
ieee: P. Hammar et al., “Single-cell screening of photosynthetic growth and
lactate production by cyanobacteria,” Biotechnology for Biofuels, vol.
8, no. 1. BioMed Central, 2015.
ista: Hammar P, Angermayr A, Sjostrom S, Van Der Meer J, Hellingwerf K, Hudson E,
Joensson H. 2015. Single-cell screening of photosynthetic growth and lactate production
by cyanobacteria. Biotechnology for Biofuels. 8(1), 193.
mla: Hammar, Petter, et al. “Single-Cell Screening of Photosynthetic Growth and
Lactate Production by Cyanobacteria.” Biotechnology for Biofuels, vol.
8, no. 1, 193, BioMed Central, 2015, doi:10.1186/s13068-015-0380-2.
short: P. Hammar, A. Angermayr, S. Sjostrom, J. Van Der Meer, K. Hellingwerf, E.
Hudson, H. Joensson, Biotechnology for Biofuels 8 (2015).
date_created: 2018-12-11T11:53:05Z
date_published: 2015-11-25T00:00:00Z
date_updated: 2021-01-12T06:52:04Z
day: '25'
ddc:
- '570'
department:
- _id: ToBo
doi: 10.1186/s13068-015-0380-2
file:
- access_level: open_access
checksum: 172b0b6f4eb2e5c22b7cec1d57dc0107
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:10:11Z
date_updated: 2020-07-14T12:45:07Z
file_id: '4796'
file_name: IST-2016-467-v1+1_s13068-015-0380-2.pdf
file_size: 2914089
relation: main_file
file_date_updated: 2020-07-14T12:45:07Z
has_accepted_license: '1'
intvolume: ' 8'
issue: '1'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
publication: Biotechnology for Biofuels
publication_status: published
publisher: BioMed Central
publist_id: '5537'
pubrep_id: '467'
quality_controlled: '1'
scopus_import: 1
status: public
title: Single-cell screening of photosynthetic growth and lactate production by cyanobacteria
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 8
year: '2015'
...
---
_id: '1810'
abstract:
- lang: eng
text: Combining antibiotics is a promising strategy for increasing treatment efficacy
and for controlling resistance evolution. When drugs are combined, their effects
on cells may be amplified or weakened, that is the drugs may show synergistic
or antagonistic interactions. Recent work revealed the underlying mechanisms of
such drug interactions by elucidating the drugs'; joint effects on cell physiology.
Moreover, new treatment strategies that use drug combinations to exploit evolutionary
tradeoffs were shown to affect the rate of resistance evolution in predictable
ways. High throughput studies have further identified drug candidates based on
their interactions with established antibiotics and general principles that enable
the prediction of drug interactions were suggested. Overall, the conceptual and
technical foundation for the rational design of potent drug combinations is rapidly
developing.
author:
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: 'Bollenbach MT. Antimicrobial interactions: Mechanisms and implications for
drug discovery and resistance evolution. Current Opinion in Microbiology.
2015;27:1-9. doi:10.1016/j.mib.2015.05.008'
apa: 'Bollenbach, M. T. (2015). Antimicrobial interactions: Mechanisms and implications
for drug discovery and resistance evolution. Current Opinion in Microbiology.
Elsevier. https://doi.org/10.1016/j.mib.2015.05.008'
chicago: 'Bollenbach, Mark Tobias. “Antimicrobial Interactions: Mechanisms and Implications
for Drug Discovery and Resistance Evolution.” Current Opinion in Microbiology.
Elsevier, 2015. https://doi.org/10.1016/j.mib.2015.05.008.'
ieee: 'M. T. Bollenbach, “Antimicrobial interactions: Mechanisms and implications
for drug discovery and resistance evolution,” Current Opinion in Microbiology,
vol. 27. Elsevier, pp. 1–9, 2015.'
ista: 'Bollenbach MT. 2015. Antimicrobial interactions: Mechanisms and implications
for drug discovery and resistance evolution. Current Opinion in Microbiology.
27, 1–9.'
mla: 'Bollenbach, Mark Tobias. “Antimicrobial Interactions: Mechanisms and Implications
for Drug Discovery and Resistance Evolution.” Current Opinion in Microbiology,
vol. 27, Elsevier, 2015, pp. 1–9, doi:10.1016/j.mib.2015.05.008.'
short: M.T. Bollenbach, Current Opinion in Microbiology 27 (2015) 1–9.
date_created: 2018-12-11T11:54:08Z
date_published: 2015-06-01T00:00:00Z
date_updated: 2021-01-12T06:53:21Z
day: '01'
ddc:
- '570'
department:
- _id: ToBo
doi: 10.1016/j.mib.2015.05.008
ec_funded: 1
file:
- access_level: open_access
checksum: 1683bb0f42ef892a5b3b71a050d65d25
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:17:23Z
date_updated: 2020-07-14T12:45:17Z
file_id: '5277'
file_name: IST-2016-493-v1+1_1-s2.0-S1369527415000594-main.pdf
file_size: 1047255
relation: main_file
file_date_updated: 2020-07-14T12:45:17Z
has_accepted_license: '1'
intvolume: ' 27'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: 1 - 9
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
- _id: 25E83C2C-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '303507'
name: Optimality principles in responses to antibiotics
- _id: 25EB3A80-B435-11E9-9278-68D0E5697425
grant_number: RGP0042/2013
name: Revealing the fundamental limits of cell growth
publication: Current Opinion in Microbiology
publication_status: published
publisher: Elsevier
publist_id: '5298'
pubrep_id: '493'
quality_controlled: '1'
scopus_import: 1
status: public
title: 'Antimicrobial interactions: Mechanisms and implications for drug discovery
and resistance evolution'
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 27
year: '2015'
...