---
_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'
...
---
_id: '9864'
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 ϕX174 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_processing_charge: No
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: de Vladar, Harold
id: 2A181218-F248-11E8-B48F-1D18A9856A87
last_name: de 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. Data from evolutionary
interplay between structure, energy and epistasis in the coat protein of the ϕX174
phage family. 2016. doi:10.6084/m9.figshare.4315652.v1
apa: Fernandes Redondo, R. A., de Vladar, H., Włodarski, T., & Bollback, J.
P. (2016). Data from evolutionary interplay between structure, energy and epistasis
in the coat protein of the ϕX174 phage family. The Royal Society. https://doi.org/10.6084/m9.figshare.4315652.v1
chicago: Fernandes Redondo, Rodrigo A, Harold de Vladar, Tomasz Włodarski, and Jonathan
P Bollback. “Data from Evolutionary Interplay between Structure, Energy and Epistasis
in the Coat Protein of the ΦX174 Phage Family.” The Royal Society, 2016. https://doi.org/10.6084/m9.figshare.4315652.v1.
ieee: R. A. Fernandes Redondo, H. de Vladar, T. Włodarski, and J. P. Bollback, “Data
from evolutionary interplay between structure, energy and epistasis in the coat
protein of the ϕX174 phage family.” The Royal Society, 2016.
ista: Fernandes Redondo RA, de Vladar H, Włodarski T, Bollback JP. 2016. Data from
evolutionary interplay between structure, energy and epistasis in the coat protein
of the ϕX174 phage family, The Royal Society, 10.6084/m9.figshare.4315652.v1.
mla: Fernandes Redondo, Rodrigo A., et al. Data from Evolutionary Interplay between
Structure, Energy and Epistasis in the Coat Protein of the ΦX174 Phage Family.
The Royal Society, 2016, doi:10.6084/m9.figshare.4315652.v1.
short: R.A. Fernandes Redondo, H. de Vladar, T. Włodarski, J.P. Bollback, (2016).
date_created: 2021-08-10T08:29:47Z
date_published: 2016-12-14T00:00:00Z
date_updated: 2023-09-20T11:56:33Z
day: '14'
department:
- _id: NiBa
- _id: JoBo
doi: 10.6084/m9.figshare.4315652.v1
main_file_link:
- open_access: '1'
url: https://doi.org/10.6084/m9.figshare.4315652.v1
month: '12'
oa: 1
oa_version: Published Version
publisher: The Royal Society
related_material:
record:
- id: '1077'
relation: used_in_publication
status: public
status: public
title: Data from evolutionary interplay between structure, energy and epistasis in
the coat protein of the ϕX174 phage family
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2016'
...
---
_id: '5554'
abstract:
- lang: eng
text: "The data stored here is used in Murat Tugrul's PhD thesis (Chapter 3), which
is related to the evolution of bacterial RNA polymerase binding.\r\nMagdalena
Steinrueck (PhD Student in Calin Guet's group at IST Austria) performed the experiments
and created the data on de novo promoter evolution. Fabienne Jesse (PhD Student
in Jon Bollback's group at IST Austria) performed the experiments and created
the data on lac promoter evolution."
article_processing_charge: No
author:
- first_name: Murat
full_name: Tugrul, Murat
id: 37C323C6-F248-11E8-B48F-1D18A9856A87
last_name: Tugrul
orcid: 0000-0002-8523-0758
citation:
ama: Tugrul M. Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase.
2016. doi:10.15479/AT:ISTA:43
apa: Tugrul, M. (2016). Experimental Data for Binding Site Evolution of Bacterial
RNA Polymerase. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:43
chicago: Tugrul, Murat. “Experimental Data for Binding Site Evolution of Bacterial
RNA Polymerase.” Institute of Science and Technology Austria, 2016. https://doi.org/10.15479/AT:ISTA:43.
ieee: M. Tugrul, “Experimental Data for Binding Site Evolution of Bacterial RNA
Polymerase.” Institute of Science and Technology Austria, 2016.
ista: Tugrul M. 2016. Experimental Data for Binding Site Evolution of Bacterial
RNA Polymerase, Institute of Science and Technology Austria, 10.15479/AT:ISTA:43.
mla: Tugrul, Murat. Experimental Data for Binding Site Evolution of Bacterial
RNA Polymerase. Institute of Science and Technology Austria, 2016, doi:10.15479/AT:ISTA:43.
short: M. Tugrul, (2016).
contributor:
- contributor_type: researcher
first_name: Magdalena
id: 2C023F40-F248-11E8-B48F-1D18A9856A87
last_name: Steinrück
- contributor_type: researcher
first_name: Fabienne
id: 4C8C26A4-F248-11E8-B48F-1D18A9856A87
last_name: Jesse
datarep_id: '43'
date_created: 2018-12-12T12:31:30Z
date_published: 2016-05-12T00:00:00Z
date_updated: 2024-02-21T13:50:34Z
day: '12'
department:
- _id: NiBa
- _id: JoBo
doi: 10.15479/AT:ISTA:43
file:
- access_level: open_access
checksum: 1fc0a10bb7ce110fcb5e1fbe3cf0c4e2
content_type: application/zip
creator: system
date_created: 2018-12-12T13:03:08Z
date_updated: 2020-07-14T12:47:01Z
file_id: '5626'
file_name: IST-2016-43-v1+1_DATA_MTugrul_PhDThesis_Chapter3.zip
file_size: 1123495
relation: main_file
file_date_updated: 2020-07-14T12:47:01Z
has_accepted_license: '1'
keyword:
- RNAP binding
- de novo promoter evolution
- lac promoter
license: https://creativecommons.org/publicdomain/zero/1.0/
month: '05'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '1131'
relation: used_in_publication
status: public
status: public
title: Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase
tmp:
image: /images/cc_0.png
legal_code_url: https://creativecommons.org/publicdomain/zero/1.0/legalcode
name: Creative Commons Public Domain Dedication (CC0 1.0)
short: CC0 (1.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2016'
...
---
_id: '1902'
abstract:
- lang: eng
text: In the 1960s-1980s, determination of bacterial growth rates was an important
tool in microbial genetics, biochemistry, molecular biology, and microbial physiology.
The exciting technical developments of the 1990s and the 2000s eclipsed that tool;
as a result, many investigators today lack experience with growth rate measurements.
Recently, investigators in a number of areas have started to use measurements
of bacterial growth rates for a variety of purposes. Those measurements have been
greatly facilitated by the availability of microwell plate readers that permit
the simultaneous measurements on up to 384 different cultures. Only the exponential
(logarithmic) portions of the resulting growth curves are useful for determining
growth rates, and manual determination of that portion and calculation of growth
rates can be tedious for high-throughput purposes. Here, we introduce the program
GrowthRates that uses plate reader output files to automatically determine the
exponential portion of the curve and to automatically calculate the growth rate,
the maximum culture density, and the duration of the growth lag phase. GrowthRates
is freely available for Macintosh, Windows, and Linux.We discuss the effects of
culture volume, the classical bacterial growth curve, and the differences between
determinations in rich media and minimal (mineral salts) media. This protocol
covers calibration of the plate reader, growth of culture inocula for both rich
and minimal media, and experimental setup. As a guide to reliability, we report
typical day-to-day variation in growth rates and variation within experiments
with respect to position of wells within the plates.
article_processing_charge: No
article_type: original
author:
- first_name: Barry
full_name: Hall, Barry
last_name: Hall
- first_name: Hande
full_name: Acar, Hande
id: 2DDF136A-F248-11E8-B48F-1D18A9856A87
last_name: Acar
orcid: 0000-0003-1986-9753
- first_name: Anna
full_name: Nandipati, Anna
last_name: Nandipati
- first_name: Miriam
full_name: Barlow, Miriam
last_name: Barlow
citation:
ama: Hall B, Acar H, Nandipati A, Barlow M. Growth rates made easy. Molecular
Biology and Evolution. 2014;31(1):232-238. doi:10.1093/molbev/mst187
apa: Hall, B., Acar, H., Nandipati, A., & Barlow, M. (2014). Growth rates made
easy. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/mst187
chicago: Hall, Barry, Hande Acar, Anna Nandipati, and Miriam Barlow. “Growth Rates
Made Easy.” Molecular Biology and Evolution. Oxford University Press, 2014.
https://doi.org/10.1093/molbev/mst187.
ieee: B. Hall, H. Acar, A. Nandipati, and M. Barlow, “Growth rates made easy,” Molecular
Biology and Evolution, vol. 31, no. 1. Oxford University Press, pp. 232–238,
2014.
ista: Hall B, Acar H, Nandipati A, Barlow M. 2014. Growth rates made easy. Molecular
Biology and Evolution. 31(1), 232–238.
mla: Hall, Barry, et al. “Growth Rates Made Easy.” Molecular Biology and Evolution,
vol. 31, no. 1, Oxford University Press, 2014, pp. 232–38, doi:10.1093/molbev/mst187.
short: B. Hall, H. Acar, A. Nandipati, M. Barlow, Molecular Biology and Evolution
31 (2014) 232–238.
date_created: 2018-12-11T11:54:37Z
date_published: 2014-01-01T00:00:00Z
date_updated: 2022-06-07T11:08:13Z
day: '01'
department:
- _id: JoBo
doi: 10.1093/molbev/mst187
external_id:
pmid:
- '24170494'
intvolume: ' 31'
issue: '1'
language:
- iso: eng
month: '01'
oa_version: None
page: 232 - 238
pmid: 1
publication: Molecular Biology and Evolution
publication_identifier:
eissn:
- 1537-1719
issn:
- 0737-4038
publication_status: published
publisher: Oxford University Press
publist_id: '5193'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Growth rates made easy
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 31
year: '2014'
...
---
_id: '2042'
abstract:
- lang: eng
text: 'Background: CRISPR is a microbial immune system likely to be involved in
host-parasite coevolution. It functions using target sequences encoded by the
bacterial genome, which interfere with invading nucleic acids using a homology-dependent
system. The system also requires protospacer associated motifs (PAMs), short motifs
close to the target sequence that are required for interference in CRISPR types
I and II. Here, we investigate whether PAMs are depleted in phage genomes due
to selection pressure to escape recognition.Results: To this end, we analyzed
two data sets. Phages infecting all bacterial hosts were analyzed first, followed
by a detailed analysis of phages infecting the genus Streptococcus, where PAMs
are best understood. We use two different measures of motif underrepresentation
that control for codon bias and the frequency of submotifs. We compare phages
infecting species with a particular CRISPR type to those infecting species without
that type. Since only known PAMs were investigated, the analysis is restricted
to CRISPR types I-C and I-E and in Streptococcus to types I-C and II. We found
evidence for PAM depletion in Streptococcus phages infecting hosts with CRISPR
type I-C, in Vibrio phages infecting hosts with CRISPR type I-E and in Streptococcus
thermopilus phages infecting hosts with type II-A, known as CRISPR3.Conclusions:
The observed motif depletion in phages with hosts having CRISPR can be attributed
to selection rather than to mutational bias, as mutational bias should affect
the phages of all hosts. This observation implies that the CRISPR system has been
efficient in the groups discussed here.'
article_number: '663'
author:
- first_name: Anne
full_name: Kupczok, Anne
id: 2BB22BC2-F248-11E8-B48F-1D18A9856A87
last_name: Kupczok
- 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: Kupczok A, Bollback JP. Motif depletion in bacteriophages infecting hosts with
CRISPR systems. BMC Genomics. 2014;15(1). doi:10.1186/1471-2164-15-663
apa: Kupczok, A., & Bollback, J. P. (2014). Motif depletion in bacteriophages
infecting hosts with CRISPR systems. BMC Genomics. BioMed Central. https://doi.org/10.1186/1471-2164-15-663
chicago: Kupczok, Anne, and Jonathan P Bollback. “Motif Depletion in Bacteriophages
Infecting Hosts with CRISPR Systems.” BMC Genomics. BioMed Central, 2014.
https://doi.org/10.1186/1471-2164-15-663.
ieee: A. Kupczok and J. P. Bollback, “Motif depletion in bacteriophages infecting
hosts with CRISPR systems,” BMC Genomics, vol. 15, no. 1. BioMed Central,
2014.
ista: Kupczok A, Bollback JP. 2014. Motif depletion in bacteriophages infecting
hosts with CRISPR systems. BMC Genomics. 15(1), 663.
mla: Kupczok, Anne, and Jonathan P. Bollback. “Motif Depletion in Bacteriophages
Infecting Hosts with CRISPR Systems.” BMC Genomics, vol. 15, no. 1, 663,
BioMed Central, 2014, doi:10.1186/1471-2164-15-663.
short: A. Kupczok, J.P. Bollback, BMC Genomics 15 (2014).
date_created: 2018-12-11T11:55:23Z
date_published: 2014-08-08T00:00:00Z
date_updated: 2021-01-12T06:54:56Z
day: '08'
ddc:
- '570'
department:
- _id: JoBo
doi: 10.1186/1471-2164-15-663
file:
- access_level: open_access
checksum: 3f6d2776b90a842a28359cc957d3d04b
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:11:24Z
date_updated: 2020-07-14T12:45:26Z
file_id: '4878'
file_name: IST-2015-396-v1+1_1471-2164-15-663.pdf
file_size: 1489769
relation: main_file
file_date_updated: 2020-07-14T12:45:26Z
has_accepted_license: '1'
intvolume: ' 15'
issue: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
publication: BMC Genomics
publication_status: published
publisher: BioMed Central
publist_id: '5009'
pubrep_id: '396'
quality_controlled: '1'
scopus_import: 1
status: public
title: Motif depletion in bacteriophages infecting hosts with CRISPR systems
tmp:
image: /images/cc_0.png
legal_code_url: https://creativecommons.org/publicdomain/zero/1.0/legalcode
name: Creative Commons Public Domain Dedication (CC0 1.0)
short: CC0 (1.0)
type: journal_article
user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87
volume: 15
year: '2014'
...
---
_id: '2412'
abstract:
- lang: eng
text: 'Background: The CRISPR/Cas system is known to act as an adaptive and heritable
immune system in Eubacteria and Archaea. Immunity is encoded in an array of spacer
sequences. Each spacer can provide specific immunity to invasive elements that
carry the same or a similar sequence. Even in closely related strains, spacer
content is very dynamic and evolves quickly. Standard models of nucleotide evolutioncannot
be applied to quantify its rate of change since processes other than single nucleotide
changes determine its evolution.Methods We present probabilistic models that are
specific for spacer content evolution. They account for the different processes
of insertion and deletion. Insertions can be constrained to occur on one end only
or are allowed to occur throughout the array. One deletion event can affect one
spacer or a whole fragment of adjacent spacers. Parameters of the underlying models
are estimated for a pair of arrays by maximum likelihood using explicit ancestor
enumeration.Results Simulations show that parameters are well estimated on average
under the models presented here. There is a bias in the rate estimation when including
fragment deletions. The models also estimate times between pairs of strains. But
with increasing time, spacer overlap goes to zero, and thus there is an upper
bound on the distance that can be estimated. Spacer content similarities are displayed
in a distance based phylogeny using the estimated times.We use the presented models
to analyze different Yersinia pestis data sets and find that the results among
them are largely congruent. The models also capture the variation in diversity
of spacers among the data sets. A comparison of spacer-based phylogenies and Cas
gene phylogenies shows that they resolve very different time scales for this data
set.Conclusions The simulations and data analyses show that the presented models
are useful for quantifying spacer content evolution and for displaying spacer
content similarities of closely related strains in a phylogeny. This allows for
comparisons of different CRISPR arrays or for comparisons between CRISPR arrays
and nucleotide substitution rates.'
author:
- first_name: Anne
full_name: Kupczok, Anne
id: 2BB22BC2-F248-11E8-B48F-1D18A9856A87
last_name: Kupczok
- 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: Kupczok A, Bollback JP. Probabilistic models for CRISPR spacer content evolution
. BMC Evolutionary Biology. 2013;13(1):54-54. doi:10.1186/1471-2148-13-54
apa: Kupczok, A., & Bollback, J. P. (2013). Probabilistic models for CRISPR
spacer content evolution . BMC Evolutionary Biology. BioMed Central. https://doi.org/10.1186/1471-2148-13-54
chicago: Kupczok, Anne, and Jonathan P Bollback. “Probabilistic Models for CRISPR
Spacer Content Evolution .” BMC Evolutionary Biology. BioMed Central, 2013.
https://doi.org/10.1186/1471-2148-13-54.
ieee: A. Kupczok and J. P. Bollback, “Probabilistic models for CRISPR spacer content
evolution ,” BMC Evolutionary Biology, vol. 13, no. 1. BioMed Central,
pp. 54–54, 2013.
ista: Kupczok A, Bollback JP. 2013. Probabilistic models for CRISPR spacer content
evolution . BMC Evolutionary Biology. 13(1), 54–54.
mla: Kupczok, Anne, and Jonathan P. Bollback. “Probabilistic Models for CRISPR Spacer
Content Evolution .” BMC Evolutionary Biology, vol. 13, no. 1, BioMed Central,
2013, pp. 54–54, doi:10.1186/1471-2148-13-54.
short: A. Kupczok, J.P. Bollback, BMC Evolutionary Biology 13 (2013) 54–54.
date_created: 2018-12-11T11:57:31Z
date_published: 2013-02-26T00:00:00Z
date_updated: 2021-01-12T06:57:20Z
day: '26'
ddc:
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department:
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doi: 10.1186/1471-2148-13-54
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publication: BMC Evolutionary Biology
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title: 'Probabilistic models for CRISPR spacer content evolution '
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