---
_id: '423'
abstract:
- lang: eng
text: Herd immunity, a process in which resistant individuals limit the spread of
a pathogen among susceptible hosts has been extensively studied in eukaryotes.
Even though bacteria have evolved multiple immune systems against their phage
pathogens, herd immunity in bacteria remains unexplored. Here we experimentally
demonstrate that herd immunity arises during phage epidemics in structured and
unstructured Escherichia coli populations consisting of differing frequencies
of susceptible and resistant cells harboring CRISPR immunity. In addition, we
develop a mathematical model that quantifies how herd immunity is affected by
spatial population structure, bacterial growth rate, and phage replication rate.
Using our model we infer a general epidemiological rule describing the relative
speed of an epidemic in partially resistant spatially structured populations.
Our experimental and theoretical findings indicate that herd immunity may be important
in bacterial communities, allowing for stable coexistence of bacteria and their
phages and the maintenance of polymorphism in bacterial immunity.
acknowledgement: "We are grateful to Remy Chait for his help and assistance with establishing
our experimental setups and to Tobias Bergmiller for valuable insights into some
specific experimental details. We thank Luciano Marraffini for donating us the pCas9
plasmid used in this study. We also want to express our gratitude to Seth Barribeau,
Andrea Betancourt, Călin Guet, Mato Lagator, Tiago Paixão and Maroš Pleška for valuable
discussions on the manuscript. Finally, we would like to thank the \r\neditors and
reviewers for their helpful comments and suggestions."
article_number: e32035
article_processing_charge: No
author:
- first_name: Pavel
full_name: Payne, Pavel
id: 35F78294-F248-11E8-B48F-1D18A9856A87
last_name: Payne
orcid: 0000-0002-2711-9453
- first_name: Lukas
full_name: Geyrhofer, Lukas
last_name: Geyrhofer
- first_name: Nicholas H
full_name: Barton, Nicholas H
id: 4880FE40-F248-11E8-B48F-1D18A9856A87
last_name: Barton
orcid: 0000-0002-8548-5240
- first_name: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
citation:
ama: Payne P, Geyrhofer L, Barton NH, Bollback JP. CRISPR-based herd immunity can
limit phage epidemics in bacterial populations. eLife. 2018;7. doi:10.7554/eLife.32035
apa: Payne, P., Geyrhofer, L., Barton, N. H., & Bollback, J. P. (2018). CRISPR-based
herd immunity can limit phage epidemics in bacterial populations. ELife.
eLife Sciences Publications. https://doi.org/10.7554/eLife.32035
chicago: Payne, Pavel, Lukas Geyrhofer, Nicholas H Barton, and Jonathan P Bollback.
“CRISPR-Based Herd Immunity Can Limit Phage Epidemics in Bacterial Populations.”
ELife. eLife Sciences Publications, 2018. https://doi.org/10.7554/eLife.32035.
ieee: P. Payne, L. Geyrhofer, N. H. Barton, and J. P. Bollback, “CRISPR-based herd
immunity can limit phage epidemics in bacterial populations,” eLife, vol.
7. eLife Sciences Publications, 2018.
ista: Payne P, Geyrhofer L, Barton NH, Bollback JP. 2018. CRISPR-based herd immunity
can limit phage epidemics in bacterial populations. eLife. 7, e32035.
mla: Payne, Pavel, et al. “CRISPR-Based Herd Immunity Can Limit Phage Epidemics
in Bacterial Populations.” ELife, vol. 7, e32035, eLife Sciences Publications,
2018, doi:10.7554/eLife.32035.
short: P. Payne, L. Geyrhofer, N.H. Barton, J.P. Bollback, ELife 7 (2018).
date_created: 2018-12-11T11:46:23Z
date_published: 2018-03-09T00:00:00Z
date_updated: 2023-09-11T12:49:17Z
day: '09'
ddc:
- '576'
department:
- _id: NiBa
- _id: JoBo
doi: 10.7554/eLife.32035
ec_funded: 1
external_id:
isi:
- '000431035800001'
file:
- access_level: open_access
checksum: 447cf6e680bdc3c01062a8737d876569
content_type: application/pdf
creator: dernst
date_created: 2018-12-17T10:36:07Z
date_updated: 2020-07-14T12:46:25Z
file_id: '5689'
file_name: 2018_eLife_Payne.pdf
file_size: 3533881
relation: main_file
file_date_updated: 2020-07-14T12:46:25Z
has_accepted_license: '1'
intvolume: ' 7'
isi: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '03'
oa: 1
oa_version: Published Version
project:
- _id: 2578D616-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '648440'
name: Selective Barriers to Horizontal Gene Transfer
publication: eLife
publication_status: published
publisher: eLife Sciences Publications
publist_id: '7400'
quality_controlled: '1'
related_material:
record:
- id: '9840'
relation: research_data
status: public
scopus_import: '1'
status: public
title: CRISPR-based herd immunity can limit phage epidemics in bacterial populations
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 7
year: '2018'
...
---
_id: '9840'
abstract:
- lang: eng
text: Herd immunity, a process in which resistant individuals limit the spread of
a pathogen among susceptible hosts has been extensively studied in eukaryotes.
Even though bacteria have evolved multiple immune systems against their phage
pathogens, herd immunity in bacteria remains unexplored. Here we experimentally
demonstrate that herd immunity arises during phage epidemics in structured and
unstructured Escherichia coli populations consisting of differing frequencies
of susceptible and resistant cells harboring CRISPR immunity. In addition, we
develop a mathematical model that quantifies how herd immunity is affected by
spatial population structure, bacterial growth rate, and phage replication rate.
Using our model we infer a general epidemiological rule describing the relative
speed of an epidemic in partially resistant spatially structured populations.
Our experimental and theoretical findings indicate that herd immunity may be important
in bacterial communities, allowing for stable coexistence of bacteria and their
phages and the maintenance of polymorphism in bacterial immunity.
article_processing_charge: No
author:
- first_name: Pavel
full_name: Payne, Pavel
id: 35F78294-F248-11E8-B48F-1D18A9856A87
last_name: Payne
orcid: 0000-0002-2711-9453
- first_name: Lukas
full_name: Geyrhofer, Lukas
last_name: Geyrhofer
- first_name: Nicholas H
full_name: Barton, Nicholas H
id: 4880FE40-F248-11E8-B48F-1D18A9856A87
last_name: Barton
orcid: 0000-0002-8548-5240
- first_name: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
citation:
ama: 'Payne P, Geyrhofer L, Barton NH, Bollback JP. Data from: CRISPR-based herd
immunity limits phage epidemics in bacterial populations. 2018. doi:10.5061/dryad.42n44'
apa: 'Payne, P., Geyrhofer, L., Barton, N. H., & Bollback, J. P. (2018). Data
from: CRISPR-based herd immunity limits phage epidemics in bacterial populations.
Dryad. https://doi.org/10.5061/dryad.42n44'
chicago: 'Payne, Pavel, Lukas Geyrhofer, Nicholas H Barton, and Jonathan P Bollback.
“Data from: CRISPR-Based Herd Immunity Limits Phage Epidemics in Bacterial Populations.”
Dryad, 2018. https://doi.org/10.5061/dryad.42n44.'
ieee: 'P. Payne, L. Geyrhofer, N. H. Barton, and J. P. Bollback, “Data from: CRISPR-based
herd immunity limits phage epidemics in bacterial populations.” Dryad, 2018.'
ista: 'Payne P, Geyrhofer L, Barton NH, Bollback JP. 2018. Data from: CRISPR-based
herd immunity limits phage epidemics in bacterial populations, Dryad, 10.5061/dryad.42n44.'
mla: 'Payne, Pavel, et al. Data from: CRISPR-Based Herd Immunity Limits Phage
Epidemics in Bacterial Populations. Dryad, 2018, doi:10.5061/dryad.42n44.'
short: P. Payne, L. Geyrhofer, N.H. Barton, J.P. Bollback, (2018).
date_created: 2021-08-09T13:10:02Z
date_published: 2018-03-12T00:00:00Z
date_updated: 2023-09-11T12:49:17Z
day: '12'
department:
- _id: NiBa
- _id: JoBo
doi: 10.5061/dryad.42n44
main_file_link:
- open_access: '1'
url: https://doi.org/10.5061/dryad.42n44
month: '03'
oa: 1
oa_version: Published Version
publisher: Dryad
related_material:
record:
- id: '423'
relation: used_in_publication
status: public
status: public
title: 'Data from: CRISPR-based herd immunity limits phage epidemics in bacterial
populations'
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2018'
...
---
_id: '67'
abstract:
- lang: eng
text: 'Gene regulatory networks evolve through rewiring of individual components—that
is, through changes in regulatory connections. However, the mechanistic basis
of regulatory rewiring is poorly understood. Using a canonical gene regulatory
system, we quantify the properties of transcription factors that determine the
evolutionary potential for rewiring of regulatory connections: robustness, tunability
and evolvability. In vivo repression measurements of two repressors at mutated
operator sites reveal their contrasting evolutionary potential: while robustness
and evolvability were positively correlated, both were in trade-off with tunability.
Epistatic interactions between adjacent operators alleviated this trade-off. A
thermodynamic model explains how the differences in robustness, tunability and
evolvability arise from biophysical characteristics of repressor–DNA binding.
The model also uncovers that the energy matrix, which describes how mutations
affect repressor–DNA binding, encodes crucial information about the evolutionary
potential of a repressor. The biophysical determinants of evolutionary potential
for regulatory rewiring constitute a mechanistic framework for understanding network
evolution.'
article_processing_charge: No
article_type: original
author:
- first_name: Claudia
full_name: Igler, Claudia
id: 46613666-F248-11E8-B48F-1D18A9856A87
last_name: Igler
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
- first_name: Gasper
full_name: Tkacik, Gasper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkacik
orcid: 0000-0002-6699-1455
- first_name: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
citation:
ama: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Evolutionary potential
of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution.
2018;2(10):1633-1643. doi:10.1038/s41559-018-0651-y
apa: Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., & Guet, C. C. (2018).
Evolutionary potential of transcription factors for gene regulatory rewiring.
Nature Ecology and Evolution. Nature Publishing Group. https://doi.org/10.1038/s41559-018-0651-y
chicago: Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin
C Guet. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.”
Nature Ecology and Evolution. Nature Publishing Group, 2018. https://doi.org/10.1038/s41559-018-0651-y.
ieee: C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Evolutionary
potential of transcription factors for gene regulatory rewiring,” Nature Ecology
and Evolution, vol. 2, no. 10. Nature Publishing Group, pp. 1633–1643, 2018.
ista: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Evolutionary potential
of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution.
2(10), 1633–1643.
mla: Igler, Claudia, et al. “Evolutionary Potential of Transcription Factors for
Gene Regulatory Rewiring.” Nature Ecology and Evolution, vol. 2, no. 10,
Nature Publishing Group, 2018, pp. 1633–43, doi:10.1038/s41559-018-0651-y.
short: C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, Nature Ecology
and Evolution 2 (2018) 1633–1643.
date_created: 2018-12-11T11:44:27Z
date_published: 2018-09-10T00:00:00Z
date_updated: 2024-03-28T23:30:49Z
day: '10'
ddc:
- '570'
department:
- _id: CaGu
- _id: GaTk
- _id: JoBo
doi: 10.1038/s41559-018-0651-y
ec_funded: 1
external_id:
isi:
- '000447947600021'
file:
- access_level: open_access
checksum: 383a2e2c944a856e2e821ec8e7bf71b6
content_type: application/pdf
creator: dernst
date_created: 2020-05-14T11:28:52Z
date_updated: 2020-07-14T12:47:37Z
file_id: '7830'
file_name: 2018_NatureEcology_Igler.pdf
file_size: 1135973
relation: main_file
file_date_updated: 2020-07-14T12:47:37Z
has_accepted_license: '1'
intvolume: ' 2'
isi: 1
issue: '10'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Submitted Version
page: 1633 - 1643
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 2578D616-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '648440'
name: Selective Barriers to Horizontal Gene Transfer
- _id: 251EE76E-B435-11E9-9278-68D0E5697425
grant_number: '24573'
name: Design principles underlying genetic switch architecture (DOC Fellowship)
publication: Nature Ecology and Evolution
publication_status: published
publisher: Nature Publishing Group
publist_id: '7987'
quality_controlled: '1'
related_material:
record:
- id: '5585'
relation: popular_science
status: public
- id: '6371'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Evolutionary potential of transcription factors for gene regulatory rewiring
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 2
year: '2018'
...
---
_id: '570'
abstract:
- lang: eng
text: 'Most phenotypes are determined by molecular systems composed of specifically
interacting molecules. However, unlike for individual components, little is known
about the distributions of mutational effects of molecular systems as a whole.
We ask how the distribution of mutational effects of a transcriptional regulatory
system differs from the distributions of its components, by first independently,
and then simultaneously, mutating a transcription factor and the associated promoter
it represses. We find that the system distribution exhibits increased phenotypic
variation compared to individual component distributions - an effect arising from
intermolecular epistasis between the transcription factor and its DNA-binding
site. In large part, this epistasis can be qualitatively attributed to the structure
of the transcriptional regulatory system and could therefore be a common feature
in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the
constraints of individual components, thereby increasing phenotypic variation
that selection could act on and facilitating adaptive evolution. '
article_number: e28921
author:
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
- first_name: Srdjan
full_name: Sarikas, Srdjan
id: 35F0286E-F248-11E8-B48F-1D18A9856A87
last_name: Sarikas
- first_name: Hande
full_name: Acar, Hande
id: 2DDF136A-F248-11E8-B48F-1D18A9856A87
last_name: Acar
orcid: 0000-0003-1986-9753
- first_name: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
citation:
ama: Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. Regulatory network structure
determines patterns of intermolecular epistasis. eLife. 2017;6. doi:10.7554/eLife.28921
apa: Lagator, M., Sarikas, S., Acar, H., Bollback, J. P., & Guet, C. C. (2017).
Regulatory network structure determines patterns of intermolecular epistasis.
ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.28921
chicago: Lagator, Mato, Srdjan Sarikas, Hande Acar, Jonathan P Bollback, and Calin
C Guet. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.”
ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.28921.
ieee: M. Lagator, S. Sarikas, H. Acar, J. P. Bollback, and C. C. Guet, “Regulatory
network structure determines patterns of intermolecular epistasis,” eLife,
vol. 6. eLife Sciences Publications, 2017.
ista: Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network
structure determines patterns of intermolecular epistasis. eLife. 6, e28921.
mla: Lagator, Mato, et al. “Regulatory Network Structure Determines Patterns of
Intermolecular Epistasis.” ELife, vol. 6, e28921, eLife Sciences Publications,
2017, doi:10.7554/eLife.28921.
short: M. Lagator, S. Sarikas, H. Acar, J.P. Bollback, C.C. Guet, ELife 6 (2017).
date_created: 2018-12-11T11:47:14Z
date_published: 2017-11-13T00:00:00Z
date_updated: 2021-01-12T08:03:15Z
day: '13'
ddc:
- '576'
department:
- _id: CaGu
- _id: JoBo
- _id: NiBa
doi: 10.7554/eLife.28921
ec_funded: 1
file:
- access_level: open_access
checksum: 273ab17f33305e4eaafd911ff88e7c5b
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:14:42Z
date_updated: 2020-07-14T12:47:10Z
file_id: '5096'
file_name: IST-2017-918-v1+1_elife-28921-figures-v3.pdf
file_size: 8453470
relation: main_file
- access_level: open_access
checksum: b433f90576c7be597cd43367946f8e7f
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:14:43Z
date_updated: 2020-07-14T12:47:10Z
file_id: '5097'
file_name: IST-2017-918-v1+2_elife-28921-v3.pdf
file_size: 1953221
relation: main_file
file_date_updated: 2020-07-14T12:47:10Z
has_accepted_license: '1'
intvolume: ' 6'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 2578D616-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '648440'
name: Selective Barriers to Horizontal Gene Transfer
publication: eLife
publication_identifier:
issn:
- 2050084X
publication_status: published
publisher: eLife Sciences Publications
publist_id: '7244'
pubrep_id: '918'
quality_controlled: '1'
scopus_import: 1
status: public
title: Regulatory network structure determines patterns of intermolecular epistasis
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: 6
year: '2017'
...
---
_id: '6291'
abstract:
- lang: eng
text: Bacteria and their pathogens – phages – are the most abundant living entities
on Earth. Throughout their coevolution, bacteria have evolved multiple immune
systems to overcome the ubiquitous threat from the phages. Although the molecu-
lar details of these immune systems’ functions are relatively well understood,
their epidemiological consequences for the phage-bacterial communities have been
largely neglected. In this thesis we employed both experimental and theoretical
methods to explore whether herd and social immunity may arise in bacterial popu-
lations. Using our experimental system consisting of Escherichia coli strains
with a CRISPR based immunity to the T7 phage we show that herd immunity arises
in phage-bacterial communities and that it is accentuated when the populations
are spatially structured. By fitting a mathematical model, we inferred expressions
for the herd immunity threshold and the velocity of spread of a phage epidemic
in partially resistant bacterial populations, which both depend on the bacterial
growth rate, phage burst size and phage latent period. We also investigated the
poten- tial for social immunity in Streptococcus thermophilus and its phage 2972
using a bioinformatic analysis of potentially coding short open reading frames
with a signalling signature, encoded within the CRISPR associated genes. Subsequently,
we tested one identified potentially signalling peptide and found that its addition
to a phage-challenged culture increases probability of survival of bacteria two
fold, although the results were only marginally significant. Together, these results
demonstrate that the ubiquitous arms races between bacteria and phages have further
consequences at the level of the population.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Pavel
full_name: Payne, Pavel
id: 35F78294-F248-11E8-B48F-1D18A9856A87
last_name: Payne
orcid: 0000-0002-2711-9453
citation:
ama: Payne P. Bacterial herd and social immunity to phages. 2017.
apa: Payne, P. (2017). Bacterial herd and social immunity to phages. Institute
of Science and Technology Austria.
chicago: Payne, Pavel. “Bacterial Herd and Social Immunity to Phages.” Institute
of Science and Technology Austria, 2017.
ieee: P. Payne, “Bacterial herd and social immunity to phages,” Institute of Science
and Technology Austria, 2017.
ista: Payne P. 2017. Bacterial herd and social immunity to phages. Institute of
Science and Technology Austria.
mla: Payne, Pavel. Bacterial Herd and Social Immunity to Phages. Institute
of Science and Technology Austria, 2017.
short: P. Payne, Bacterial Herd and Social Immunity to Phages, Institute of Science
and Technology Austria, 2017.
date_created: 2019-04-09T15:16:45Z
date_published: 2017-02-01T00:00:00Z
date_updated: 2023-09-07T12:00:00Z
day: '01'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: NiBa
- _id: JoBo
file:
- access_level: closed
checksum: a0fc5c26a89c0ea759947ffba87d0d8f
content_type: application/pdf
creator: dernst
date_created: 2019-04-09T15:15:32Z
date_updated: 2020-07-14T12:47:27Z
file_id: '6292'
file_name: thesis_pavel_payne_final_w_signature_page.pdf
file_size: 3025175
relation: main_file
- access_level: open_access
checksum: af531e921a7f64a9e0af4cd8783b2226
content_type: application/pdf
creator: dernst
date_created: 2021-02-22T13:45:59Z
date_updated: 2021-02-22T13:45:59Z
file_id: '9187'
file_name: 2017_Payne_Thesis.pdf
file_size: 3111536
relation: main_file
success: 1
file_date_updated: 2021-02-22T13:45:59Z
has_accepted_license: '1'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: '83'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
- first_name: Nicholas H
full_name: Barton, Nicholas H
id: 4880FE40-F248-11E8-B48F-1D18A9856A87
last_name: Barton
orcid: 0000-0002-8548-5240
title: Bacterial herd and social immunity to phages
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2017'
...
---
_id: '820'
abstract:
- lang: eng
text: "The lac operon is a classic model system for bacterial gene regulation, and
has been studied extensively in E. coli, a classic model organism. However, not
much is known about E. coli’s ecology and life outside the laboratory, in particular
in soil and water environments. The natural diversity of the lac operon outside
the laboratory, its role in the ecology of E. coli and the selection pressures
it is exposed to, are similarly unknown.\r\nIn Chapter Two of this thesis, I explore
the genetic diversity, phylogenetic history and signatures of selection of the
lac operon across 20 natural isolates of E. coli and divergent clades of Escherichia.
I found that complete lac operons were present in all isolates examined, which
in all but one case were functional. The lac operon phylogeny conformed to the
whole-genome phylogeny of the divergent Escherichia clades, which excludes horizontal
gene transfer as an explanation for the presence of functional lac operons in
these clades. All lac operon genes showed a signature of purifying selection;
this signature was strongest for the lacY gene. Lac operon genes of human and
environmental isolates showed similar signatures of selection, except the lacZ
gene, which showed a stronger signature of selection in environmental isolates.\r\nIn
Chapter Three, I try to identify the natural genetic variation relevant for phenotype
and fitness in the lac operon, comparing growth rate on lactose and LacZ activity
of the lac operons of these wild isolates in a common genetic background. Sequence
variation in the lac promoter region, upstream of the -10 and -35 RNA polymerase
binding motif, predicted variation in LacZ activity at full induction, using a
thermodynamic model of polymerase binding (Tugrul, 2016). However, neither variation
in LacZ activity, nor RNA polymerase binding predicted by the model correlated
with variation in growth rate. Lac operons of human and environmental isolates
did not differ systematically in either growth rate on lactose or LacZ protein
activity, suggesting that these lac operons have been exposed to similar selection
pressures. We thus have no evidence that the phenotypic variation we measured
is relevant for fitness.\r\nTo start assessing the effect of genomic background
on the growth phenotype conferred by the lac operon, I compared growth on minimal
medium with lactose between lac operon constructs and the corresponding original
isolates, I found that maximal growth rate was determined by genomic background,
with almost all backgrounds conferring higher growth rates than lab strain K12
MG1655. However, I found no evidence that the lactose concentration at which growth
was half maximal depended on genomic background."
acknowledgement: "ERC H2020 programme (grant agreement no. 648440)\r\nThanks to Jon
Bollback for giving me the chance to do this work, for sharing the ideas that lay
at the basis of this work, for his honesty and openness, showing himself to me as
a person and not just as a boss. Thanks to Nick Barton for his guidance at the last
stage, reading and commenting extensively on several versions of this manuscript,
and for his encouragement; thanks to both Jon and Nick for their kindness and patience.
Thanks to Erik van Nimwegen and Calin Guet for their time and willingness to be
in my thesis committee, and to Erik van Nimwegen especially for agreeing to enter
my thesis committee at the last moment, and for his very sharp, helpful and relevant
comments during and after the defense. Thanks to my collaborators and discussion
partners: Anne Kupczok, for her guidance, ideas and discussions during the construction
of the manuscript of Chapter Two, and her comments on the manuscript; Georg Rieckh
for making me aware of the issue of parameter identifiability, suggesting how to
solve it, and for his unfortunate idea to start the plasmid enterprise in the first
place; Murat Tugrul for sharing his model, for his enthusiasm, and his comments
on Chapter Three; Srdjan Sarikas for his collaboration on the Monod model fitting,
fast forwarding the analysis to turbo speed and making beautiful figures, and making
the discussion fun on top of it all; Vanessa Barone for her last minute comments,
especially on Chapter Three, providing a sharp and very helpful experimentalist
perspective at the last moment; Maros Pleska and Marjon de Vos for their comments
on the manuscript of Chapter Two; Gasper Tkacik for his crucial input on the relation
between growth rate and lactose concentration; Bor Kavcic for his input on growth
rate modeling and error propagation. Thanks to the Bollback, Bollenbach, Barton,
Guet and Tkacik group members for both pro- viding an inspiring and supportive scientific
environment to work in, as well as a lot of warmth and colour to everyday life.
And thanks to the friends I found here, to the people who were there for me and
to the people who changed my life, making it stranger and more beautiful than I
could have imagined, Maros, Vanessa, Tade, Suzi, Andrej, Peter, Tiago, Kristof,
Karin, Irene, Misha, Mato, Guillaume and Zanin. "
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Fabienne
full_name: Jesse, Fabienne
id: 4C8C26A4-F248-11E8-B48F-1D18A9856A87
last_name: Jesse
citation:
ama: Jesse F. The lac operon in the wild. 2017. doi:10.15479/AT:ISTA:th_857
apa: Jesse, F. (2017). The lac operon in the wild. Institute of Science and
Technology Austria. https://doi.org/10.15479/AT:ISTA:th_857
chicago: Jesse, Fabienne. “The Lac Operon in the Wild.” Institute of Science and
Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:th_857.
ieee: F. Jesse, “The lac operon in the wild,” Institute of Science and Technology
Austria, 2017.
ista: Jesse F. 2017. The lac operon in the wild. Institute of Science and Technology
Austria.
mla: Jesse, Fabienne. The Lac Operon in the Wild. Institute of Science and
Technology Austria, 2017, doi:10.15479/AT:ISTA:th_857.
short: F. Jesse, The Lac Operon in the Wild, Institute of Science and Technology
Austria, 2017.
date_created: 2018-12-11T11:48:41Z
date_published: 2017-08-25T00:00:00Z
date_updated: 2023-09-07T12:01:21Z
day: '25'
ddc:
- '576'
- '577'
- '579'
degree_awarded: PhD
department:
- _id: JoBo
doi: 10.15479/AT:ISTA:th_857
ec_funded: 1
file:
- access_level: open_access
checksum: c62257a7bff0c5f39e1abffc6bfcca5c
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:17:00Z
date_updated: 2020-07-14T12:48:10Z
file_id: '5252'
file_name: IST-2017-857-v1+1_thesis_fabienne.pdf
file_size: 3417773
relation: main_file
- access_level: closed
checksum: fc87d7d72fce52824a3ae7dcad0413a8
content_type: application/x-tex
creator: dernst
date_created: 2019-04-05T08:51:59Z
date_updated: 2020-07-14T12:48:10Z
file_id: '6212'
file_name: 2017_thesis_Jesse_source.tex
file_size: 215899
relation: source_file
file_date_updated: 2020-07-14T12:48:10Z
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '87'
project:
- _id: 2578D616-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '648440'
name: Selective Barriers to Horizontal Gene Transfer
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '6829'
pubrep_id: '857'
status: public
supervisor:
- first_name: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
title: The lac operon in the wild
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: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2017'
...
---
_id: '1077'
abstract:
- lang: eng
text: Viral capsids are structurally constrained by interactions among the amino
acids (AAs) of their constituent proteins. Therefore, epistasis is expected to
evolve among physically interacting sites and to influence the rates of substitution.
To study the evolution of epistasis, we focused on the major structural protein
of the fX174 phage family by first reconstructing the ancestral protein sequences
of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction
differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each
ancestral haplotype and the extant species, we estimated, in silico, the distribution
of free energies and epistasis of the capsid structure. We found that free energy
has not significantly increased but epistasis has. We decomposed epistasis up
to fifth order and found that higher-order epistasis sometimes compensates pairwise
interactions making the free energy seem additive. The dN/dS ratio is low, suggesting
strong purifying selection, and that structure is under stabilizing selection.
We synthesized phages carrying ancestral haplotypes of the coat protein gene and
measured their fitness experimentally. Our findings indicate that stabilizing
mutations can have higher fitness, and that fitness optima do not necessarily
coincide with energy minima.
article_number: '20160139'
article_processing_charge: Yes (in subscription journal)
author:
- first_name: Rodrigo A
full_name: Fernandes Redondo, Rodrigo A
id: 409D5C96-F248-11E8-B48F-1D18A9856A87
last_name: Fernandes Redondo
orcid: 0000-0002-5837-2793
- first_name: Harold
full_name: Vladar, Harold
id: 2A181218-F248-11E8-B48F-1D18A9856A87
last_name: Vladar
orcid: 0000-0002-5985-7653
- first_name: Tomasz
full_name: Włodarski, Tomasz
last_name: Włodarski
- first_name: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
citation:
ama: Fernandes Redondo RA, de Vladar H, Włodarski T, Bollback JP. Evolutionary interplay
between structure, energy and epistasis in the coat protein of the ϕX174 phage
family. Journal of the Royal Society Interface. 2017;14(126). doi:10.1098/rsif.2016.0139
apa: Fernandes Redondo, R. A., de Vladar, H., Włodarski, T., & Bollback, J.
P. (2017). Evolutionary interplay between structure, energy and epistasis in the
coat protein of the ϕX174 phage family. Journal of the Royal Society Interface.
Royal Society of London. https://doi.org/10.1098/rsif.2016.0139
chicago: Fernandes Redondo, Rodrigo A, Harold de Vladar, Tomasz Włodarski, and Jonathan
P Bollback. “Evolutionary Interplay between Structure, Energy and Epistasis in
the Coat Protein of the ΦX174 Phage Family.” Journal of the Royal Society Interface.
Royal Society of London, 2017. https://doi.org/10.1098/rsif.2016.0139.
ieee: R. A. Fernandes Redondo, H. de Vladar, T. Włodarski, and J. P. Bollback, “Evolutionary
interplay between structure, energy and epistasis in the coat protein of the ϕX174
phage family,” Journal of the Royal Society Interface, vol. 14, no. 126.
Royal Society of London, 2017.
ista: Fernandes Redondo RA, de Vladar H, Włodarski T, Bollback JP. 2017. Evolutionary
interplay between structure, energy and epistasis in the coat protein of the ϕX174
phage family. Journal of the Royal Society Interface. 14(126), 20160139.
mla: Fernandes Redondo, Rodrigo A., et al. “Evolutionary Interplay between Structure,
Energy and Epistasis in the Coat Protein of the ΦX174 Phage Family.” Journal
of the Royal Society Interface, vol. 14, no. 126, 20160139, Royal Society
of London, 2017, doi:10.1098/rsif.2016.0139.
short: R.A. Fernandes Redondo, H. de Vladar, T. Włodarski, J.P. Bollback, Journal
of the Royal Society Interface 14 (2017).
date_created: 2018-12-11T11:50:01Z
date_published: 2017-01-04T00:00:00Z
date_updated: 2023-09-20T11:56:34Z
day: '04'
ddc:
- '570'
department:
- _id: NiBa
- _id: JoBo
doi: 10.1098/rsif.2016.0139
ec_funded: 1
external_id:
isi:
- '000393380400001'
file:
- access_level: open_access
content_type: application/pdf
creator: dernst
date_created: 2019-01-18T09:14:02Z
date_updated: 2019-01-18T09:14:02Z
file_id: '5843'
file_name: 2017_JRSI_Redondo.pdf
file_size: 1092015
relation: main_file
success: 1
file_date_updated: 2019-01-18T09:14:02Z
has_accepted_license: '1'
intvolume: ' 14'
isi: 1
issue: '126'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
project:
- _id: 25B07788-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '250152'
name: Limits to selection in biology and in evolutionary computation
- _id: 2578D616-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '648440'
name: Selective Barriers to Horizontal Gene Transfer
publication: Journal of the Royal Society Interface
publication_identifier:
issn:
- '17425689'
publication_status: published
publisher: Royal Society of London
publist_id: '6303'
quality_controlled: '1'
related_material:
record:
- id: '9864'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Evolutionary interplay between structure, energy and epistasis in the coat
protein of the ϕX174 phage family
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 14
year: '2017'
...
---
_id: '954'
abstract:
- lang: eng
text: Understanding the relation between genotype and phenotype remains a major
challenge. The difficulty of predicting individual mutation effects, and particularly
the interactions between them, has prevented the development of a comprehensive
theory that links genotypic changes to their phenotypic effects. We show that
a general thermodynamic framework for gene regulation, based on a biophysical
understanding of protein-DNA binding, accurately predicts the sign of epistasis
in a canonical cis-regulatory element consisting of overlapping RNA polymerase
and repressor binding sites. Sign and magnitude of individual mutation effects
are sufficient to predict the sign of epistasis and its environmental dependence.
Thus, the thermodynamic model offers the correct null prediction for epistasis
between mutations across DNA-binding sites. Our results indicate that a predictive
theory for the effects of cis-regulatory mutations is possible from first principles,
as long as the essential molecular mechanisms and the constraints these impose
on a biological system are accounted for.
article_number: e25192
article_processing_charge: Yes
author:
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
- first_name: Tiago
full_name: Paixao, Tiago
id: 2C5658E6-F248-11E8-B48F-1D18A9856A87
last_name: Paixao
orcid: 0000-0003-2361-3953
- first_name: Nicholas H
full_name: Barton, Nicholas H
id: 4880FE40-F248-11E8-B48F-1D18A9856A87
last_name: Barton
orcid: 0000-0002-8548-5240
- first_name: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
citation:
ama: Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. On the mechanistic nature
of epistasis in a canonical cis-regulatory element. eLife. 2017;6. doi:10.7554/eLife.25192
apa: Lagator, M., Paixao, T., Barton, N. H., Bollback, J. P., & Guet, C. C.
(2017). On the mechanistic nature of epistasis in a canonical cis-regulatory element.
ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25192
chicago: Lagator, Mato, Tiago Paixao, Nicholas H Barton, Jonathan P Bollback, and
Calin C Guet. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory
Element.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25192.
ieee: M. Lagator, T. Paixao, N. H. Barton, J. P. Bollback, and C. C. Guet, “On the
mechanistic nature of epistasis in a canonical cis-regulatory element,” eLife,
vol. 6. eLife Sciences Publications, 2017.
ista: Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. 2017. On the mechanistic
nature of epistasis in a canonical cis-regulatory element. eLife. 6, e25192.
mla: Lagator, Mato, et al. “On the Mechanistic Nature of Epistasis in a Canonical
Cis-Regulatory Element.” ELife, vol. 6, e25192, eLife Sciences Publications,
2017, doi:10.7554/eLife.25192.
short: M. Lagator, T. Paixao, N.H. Barton, J.P. Bollback, C.C. Guet, ELife 6 (2017).
date_created: 2018-12-11T11:49:23Z
date_published: 2017-05-18T00:00:00Z
date_updated: 2023-09-22T10:01:17Z
day: '18'
ddc:
- '576'
department:
- _id: CaGu
- _id: NiBa
- _id: JoBo
doi: 10.7554/eLife.25192
ec_funded: 1
external_id:
isi:
- '000404024800001'
file:
- access_level: open_access
checksum: 59cdd4400fb41280122d414fea971546
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:17:49Z
date_updated: 2020-07-14T12:48:16Z
file_id: '5306'
file_name: IST-2017-841-v1+1_elife-25192-v2.pdf
file_size: 2441529
relation: main_file
- access_level: open_access
checksum: b69024880558b858eb8c5d47a92b6377
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:17:50Z
date_updated: 2020-07-14T12:48:16Z
file_id: '5307'
file_name: IST-2017-841-v1+2_elife-25192-figures-v2.pdf
file_size: 3752660
relation: main_file
file_date_updated: 2020-07-14T12:48:16Z
has_accepted_license: '1'
intvolume: ' 6'
isi: 1
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 25B1EC9E-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618091'
name: Speed of Adaptation in Population Genetics and Evolutionary Computation
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 2578D616-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '648440'
name: Selective Barriers to Horizontal Gene Transfer
publication: eLife
publication_identifier:
issn:
- 2050084X
publication_status: published
publisher: eLife Sciences Publications
publist_id: '6460'
pubrep_id: '841'
quality_controlled: '1'
scopus_import: '1'
status: public
title: On the mechanistic nature of epistasis in a canonical cis-regulatory element
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 6
year: '2017'
...
---
_id: '1427'
abstract:
- lang: eng
text: Changes in gene expression are an important mode of evolution; however, the
proximate mechanism of these changes is poorly understood. In particular, little
is known about the effects of mutations within cis binding sites for transcription
factors, or the nature of epistatic interactions between these mutations. Here,
we tested the effects of single and double mutants in two cis binding sites involved
in the transcriptional regulation of the Escherichia coli araBAD operon, a component
of arabinose metabolism, using a synthetic system. This system decouples transcriptional
control from any posttranslational effects on fitness, allowing a precise estimate
of the effect of single and double mutations, and hence epistasis, on gene expression.
We found that epistatic interactions between mutations in the araBAD cis-regulatory
element are common, and that the predominant form of epistasis is negative. The
magnitude of the interactions depended on whether the mutations are located in
the same or in different operator sites. Importantly, these epistatic interactions
were dependent on the presence of arabinose, a native inducer of the araBAD operon
in vivo, with some interactions changing in sign (e.g., from negative to positive)
in its presence. This study thus reveals that mutations in even relatively simple
cis-regulatory elements interact in complex ways such that selection on the level
of gene expression in one environment might perturb regulation in the other environment
in an unpredictable and uncorrelated manner.
author:
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
- first_name: Claudia
full_name: Igler, Claudia
id: 46613666-F248-11E8-B48F-1D18A9856A87
last_name: Igler
- first_name: Anaisa
full_name: Moreno, Anaisa
last_name: Moreno
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
citation:
ama: Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. Epistatic interactions
in the arabinose cis-regulatory element. Molecular Biology and Evolution.
2016;33(3):761-769. doi:10.1093/molbev/msv269
apa: Lagator, M., Igler, C., Moreno, A., Guet, C. C., & Bollback, J. P. (2016).
Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology
and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv269
chicago: Lagator, Mato, Claudia Igler, Anaisa Moreno, Calin C Guet, and Jonathan
P Bollback. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.”
Molecular Biology and Evolution. Oxford University Press, 2016. https://doi.org/10.1093/molbev/msv269.
ieee: M. Lagator, C. Igler, A. Moreno, C. C. Guet, and J. P. Bollback, “Epistatic
interactions in the arabinose cis-regulatory element,” Molecular Biology and
Evolution, vol. 33, no. 3. Oxford University Press, pp. 761–769, 2016.
ista: Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. 2016. Epistatic interactions
in the arabinose cis-regulatory element. Molecular Biology and Evolution. 33(3),
761–769.
mla: Lagator, Mato, et al. “Epistatic Interactions in the Arabinose Cis-Regulatory
Element.” Molecular Biology and Evolution, vol. 33, no. 3, Oxford University
Press, 2016, pp. 761–69, doi:10.1093/molbev/msv269.
short: M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology
and Evolution 33 (2016) 761–769.
date_created: 2018-12-11T11:51:57Z
date_published: 2016-03-01T00:00:00Z
date_updated: 2021-01-12T06:50:39Z
day: '01'
ddc:
- '570'
- '576'
department:
- _id: CaGu
- _id: JoBo
doi: 10.1093/molbev/msv269
ec_funded: 1
file:
- access_level: open_access
checksum: 1f456ce1d2aa2f67176a1709f9702ecf
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:09:27Z
date_updated: 2020-07-14T12:44:53Z
file_id: '4751'
file_name: IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf
file_size: 648115
relation: main_file
file_date_updated: 2020-07-14T12:44:53Z
has_accepted_license: '1'
intvolume: ' 33'
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: 761 - 769
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: Molecular Biology and Evolution
publication_status: published
publisher: Oxford University Press
publist_id: '5772'
pubrep_id: '588'
quality_controlled: '1'
scopus_import: 1
status: public
title: Epistatic interactions in the arabinose cis-regulatory element
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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 33
year: '2016'
...
---
_id: '1121'
abstract:
- lang: eng
text: "Horizontal gene transfer (HGT), the lateral acquisition of genes across existing
species\r\nboundaries, is a major evolutionary force shaping microbial genomes
that facilitates\r\nadaptation to new environments as well as resistance to antimicrobial
drugs. As such,\r\nunderstanding the mechanisms and constraints that determine
the outcomes of HGT\r\nevents is crucial to understand the dynamics of HGT and
to design better strategies to\r\novercome the challenges that originate from
it.\r\nFollowing the insertion and expression of a newly transferred gene, the
success of an\r\nHGT event will depend on the fitness effect it has on the recipient
(host) cell. Therefore,\r\npredicting the impact of HGT on the genetic composition
of a population critically\r\ndepends on the distribution of fitness effects (DFE)
of horizontally transferred genes.\r\nHowever, to date, we have little knowledge
of the DFE of newly transferred genes, and\r\nhence little is known about the
shape and scale of this distribution.\r\nIt is particularly important to better
understand the selective barriers that determine\r\nthe fitness effects of newly
transferred genes. In spite of substantial bioinformatics\r\nefforts to identify
horizontally transferred genes and selective barriers, a systematic\r\nexperimental
approach to elucidate the roles of different selective barriers in defining\r\nthe
fate of a transfer event has largely been absent. Similarly, although the fact
that\r\nenvironment might alter the fitness effect of a horizontally transferred
gene may seem\r\nobvious, little attention has been given to it in a systematic
experimental manner.\r\nIn this study, we developed a systematic experimental
approach that consists of\r\ntransferring 44 arbitrarily selected Salmonella typhimurium
orthologous genes into an\r\nEscherichia coli host, and estimating the fitness
effects of these transferred genes at a\r\nconstant expression level by performing
competition assays against the wild type.\r\nIn chapter 2, we performed one-to-one
competition assays between a mutant strain\r\ncarrying a transferred gene and
the wild type strain. By using flow cytometry we\r\nestimated selection coefficients
for the transferred genes with a precision level of 10-3,and obtained the DFE
of horizontally transferred genes. We then investigated if these\r\nfitness effects
could be predicted by any of the intrinsic properties of the genes, namely,\r\nfunctional
category, degree of complexity (protein-protein interactions), GC content,\r\ncodon
usage and length. Our analyses revealed that the functional category and length\r\nof
the genes act as potential selective barriers. Finally, using the same procedure
with\r\nthe endogenous E. coli orthologs of these 44 genes, we demonstrated that
gene dosage is\r\nthe most prominent selective barrier to HGT.\r\nIn chapter 3,
using the same set of genes we investigated the role of environment on the\r\nsuccess
of HGT events. Under six different environments with different levels of stress\r\nwe
performed more complex competition assays, where we mixed all 44 mutant strains\r\ncarrying
transferred genes with the wild type strain. To estimate the fitness effects of\r\ngenes
relative to wild type we used next generation sequencing. We found that the DFEs\r\nof
horizontally transferred genes are highly dependent on the environment, with\r\nabundant
gene–by-environment interactions. Furthermore, we demonstrated a\r\nrelationship
between average fitness effect of a gene across all environments and its\r\nenvironmental
variance, and thus its predictability. Finally, in spite of the fitness effects\r\nof
genes being highly environment-dependent, we still observed a common shape of\r\nDFEs
across all tested environments."
acknowledgement: "This study was supported by European Research Council ERC CoG 2014
– EVOLHGT,\r\nunder the grant number 648440.\r\n\r\nIt is a pleasure to thank the
many people who made this thesis possible.\r\nI would like to first thank my advisor,
Jonathan Paul Bollback for providing guidance in\r\nall aspects of my life, encouragement,
sound advice, and good teaching over the last six\r\nyears.\r\nI would also like
to thank the members of my dissertation committee – Călin C. Guet\r\nand John F.
Baines – not only for their time and guidance, but for their intellectual\r\ncontributions
to my development as a scientist.\r\nI would like to thank Flavia Gama and Rodrigo
Redondo who have taught me all the\r\nskills in the laboratory with their graciousness
and friendship. Also special thanks to\r\nBollback group for their support and for
providing a stimulating and fun environment:\r\nIsabella Tomanek, Fabienne Jesse,
Claudia Igler, and Pavel Payne.\r\nJerneja Beslagic is not only an amazing assistant,
she also has a smile brighter and\r\nwarmer than the sunshine, bringing happiness
to every moment. Always keep your light\r\nNeja, I will miss our invaluable chatters
a lot."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Hande
full_name: Acar, Hande
id: 2DDF136A-F248-11E8-B48F-1D18A9856A87
last_name: Acar
orcid: 0000-0003-1986-9753
citation:
ama: Acar H. Selective barriers to horizontal gene transfer. 2016.
apa: Acar, H. (2016). Selective barriers to horizontal gene transfer. Institute
of Science and Technology Austria.
chicago: Acar, Hande. “Selective Barriers to Horizontal Gene Transfer.” Institute
of Science and Technology Austria, 2016.
ieee: H. Acar, “Selective barriers to horizontal gene transfer,” Institute of Science
and Technology Austria, 2016.
ista: Acar H. 2016. Selective barriers to horizontal gene transfer. Institute of
Science and Technology Austria.
mla: Acar, Hande. Selective Barriers to Horizontal Gene Transfer. Institute
of Science and Technology Austria, 2016.
short: H. Acar, Selective Barriers to Horizontal Gene Transfer, Institute of Science
and Technology Austria, 2016.
date_created: 2018-12-11T11:50:16Z
date_published: 2016-12-01T00:00:00Z
date_updated: 2023-09-07T11:42:26Z
day: '01'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: JoBo
ec_funded: 1
file:
- access_level: closed
checksum: 94bbbc754c36115bf37f8fc11fad43c4
content_type: application/pdf
creator: dernst
date_created: 2019-08-13T11:17:50Z
date_updated: 2019-08-13T11:17:50Z
file_id: '6814'
file_name: PhDThesis_HandeAcar_1230.pdf
file_size: 3682711
relation: main_file
- access_level: open_access
checksum: 94bbbc754c36115bf37f8fc11fad43c4
content_type: application/pdf
creator: dernst
date_created: 2021-02-22T11:51:13Z
date_updated: 2021-02-22T11:51:13Z
file_id: '9184'
file_name: 2016_Thesis_HandeAcar.pdf
file_size: 3682711
relation: main_file
success: 1
file_date_updated: 2021-02-22T11:51:13Z
has_accepted_license: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: '75'
project:
- _id: 2578D616-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '648440'
name: Selective Barriers to Horizontal Gene Transfer
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '6239'
status: public
supervisor:
- first_name: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
title: Selective barriers to horizontal gene transfer
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2016'
...