---
_id: '1131'
abstract:
- lang: eng
text: "Evolution of gene regulation is important for phenotypic evolution and diversity.
Sequence-specific binding of regulatory proteins is one of the key regulatory
mechanisms determining gene expression. Although there has been intense interest
in evolution of regulatory binding sites in the last decades, a theoretical understanding
is far from being complete. In this thesis, I aim at a better understanding of
the evolution of transcriptional regulatory binding sequences by using biophysical
and population genetic models.\r\nIn the first part of the thesis, I discuss how
to formulate the evolutionary dynamics of binding se- quences in a single isolated
binding site and in promoter/enhancer regions. I develop a theoretical framework
bridging between a thermodynamical model for transcription and a mutation-selection-drift
model for monomorphic populations. I mainly address the typical evolutionary rates,
and how they de- pend on biophysical parameters (e.g. binding length and specificity)
and population genetic parameters (e.g. population size and selection strength).\r\nIn
the second part of the thesis, I analyse empirical data for a better evolutionary
and biophysical understanding of sequence-specific binding of bacterial RNA polymerase.
First, I infer selection on regulatory and non-regulatory binding sites of RNA
polymerase in the E. coli K12 genome. Second, I infer the chemical potential of
RNA polymerase, an important but unknown physical parameter defining the threshold
energy for strong binding. Furthermore, I try to understand the relation between
the lac promoter sequence diversity and the LacZ activity variation among 20 bacterial
isolates by constructing a simple but biophysically motivated gene expression
model. Lastly, I lay out a statistical framework to predict adaptive point mutations
in de novo promoter evolution in a selection experiment."
acknowledgement: This PhD thesis may not have been completed without the help and
care I received from some peo- ple during my PhD life. I am especially grateful
to Tiago Paixao, Gasper Tkacik, Nick Barton, not only for their scientific advices
but also for their patience and support. I thank Calin Guet and Jonathan Bollback
for allowing me to “play around” in their labs and get some experience on experimental
evolution. I thank Magdalena Steinrueck and Fabienne Jesse for collaborating and
sharing their experimental data with me. I thank Johannes Jaeger for reviewing my
thesis. I thank all members of Barton group (aka bartonians) for their feedback,
and all workers of IST Austria for making the best working conditions. Lastly, I
thank two special women, Nejla Sag ̆lam and Setenay Dog ̆an, for their continuous
support and encouragement. I truly had a great chance of having right people around
me.
alternative_title:
- ISTA Thesis
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. Evolution of transcriptional regulatory sequences. 2016.
apa: Tugrul, M. (2016). Evolution of transcriptional regulatory sequences.
Institute of Science and Technology Austria.
chicago: Tugrul, Murat. “Evolution of Transcriptional Regulatory Sequences.” Institute
of Science and Technology Austria, 2016.
ieee: M. Tugrul, “Evolution of transcriptional regulatory sequences,” Institute
of Science and Technology Austria, 2016.
ista: Tugrul M. 2016. Evolution of transcriptional regulatory sequences. Institute
of Science and Technology Austria.
mla: Tugrul, Murat. Evolution of Transcriptional Regulatory Sequences. Institute
of Science and Technology Austria, 2016.
short: M. Tugrul, Evolution of Transcriptional Regulatory Sequences, Institute of
Science and Technology Austria, 2016.
date_created: 2018-12-11T11:50:19Z
date_published: 2016-07-01T00:00:00Z
date_updated: 2024-02-21T13:50:34Z
day: '01'
ddc:
- '576'
degree_awarded: PhD
department:
- _id: NiBa
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creator: dernst
date_created: 2021-02-22T11:45:20Z
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language:
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oa: 1
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page: '89'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '6229'
related_material:
record:
- id: '1666'
relation: part_of_dissertation
status: public
- id: '5554'
relation: research_data
status: public
status: public
supervisor:
- first_name: Nicholas H
full_name: Barton, Nicholas H
id: 4880FE40-F248-11E8-B48F-1D18A9856A87
last_name: Barton
orcid: 0000-0002-8548-5240
title: Evolution of transcriptional regulatory sequences
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
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:
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checksum: 1fc0a10bb7ce110fcb5e1fbe3cf0c4e2
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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:
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relation: used_in_publication
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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: '1883'
abstract:
- lang: eng
text: "We introduce a one-parametric family of tree growth models, in which branching
probabilities decrease with branch age τ as τ-α. Depending on the exponent α,
the scaling of tree depth with tree size n displays a transition between the logarithmic
scaling of random trees and an algebraic growth. At the transition (α=1) tree
depth grows as (logn)2. This anomalous scaling is in good agreement with the trend
observed in evolution of biological species, thus providing a theoretical support
for age-dependent speciation and associating it to the occurrence of a critical
point.\r\n"
article_number: '022803'
article_processing_charge: No
article_type: original
author:
- first_name: Stephanie
full_name: Keller-Schmidt, Stephanie
last_name: Keller-Schmidt
- first_name: Murat
full_name: Tugrul, Murat
id: 37C323C6-F248-11E8-B48F-1D18A9856A87
last_name: Tugrul
orcid: 0000-0002-8523-0758
- first_name: Víctor
full_name: Eguíluz, Víctor
last_name: Eguíluz
- first_name: Emilio
full_name: Hernandez Garcia, Emilio
last_name: Hernandez Garcia
- first_name: Konstantin
full_name: Klemm, Konstantin
last_name: Klemm
citation:
ama: Keller-Schmidt S, Tugrul M, Eguíluz V, Hernandez Garcia E, Klemm K. Anomalous
scaling in an age-dependent branching model. Physical Review E Statistical
Nonlinear and Soft Matter Physics. 2015;91(2). doi:10.1103/PhysRevE.91.022803
apa: Keller-Schmidt, S., Tugrul, M., Eguíluz, V., Hernandez Garcia, E., & Klemm,
K. (2015). Anomalous scaling in an age-dependent branching model. Physical
Review E Statistical Nonlinear and Soft Matter Physics. American Institute
of Physics. https://doi.org/10.1103/PhysRevE.91.022803
chicago: Keller-Schmidt, Stephanie, Murat Tugrul, Víctor Eguíluz, Emilio Hernandez
Garcia, and Konstantin Klemm. “Anomalous Scaling in an Age-Dependent Branching
Model.” Physical Review E Statistical Nonlinear and Soft Matter Physics.
American Institute of Physics, 2015. https://doi.org/10.1103/PhysRevE.91.022803.
ieee: S. Keller-Schmidt, M. Tugrul, V. Eguíluz, E. Hernandez Garcia, and K. Klemm,
“Anomalous scaling in an age-dependent branching model,” Physical Review E
Statistical Nonlinear and Soft Matter Physics, vol. 91, no. 2. American Institute
of Physics, 2015.
ista: Keller-Schmidt S, Tugrul M, Eguíluz V, Hernandez Garcia E, Klemm K. 2015.
Anomalous scaling in an age-dependent branching model. Physical Review E Statistical
Nonlinear and Soft Matter Physics. 91(2), 022803.
mla: Keller-Schmidt, Stephanie, et al. “Anomalous Scaling in an Age-Dependent Branching
Model.” Physical Review E Statistical Nonlinear and Soft Matter Physics,
vol. 91, no. 2, 022803, American Institute of Physics, 2015, doi:10.1103/PhysRevE.91.022803.
short: S. Keller-Schmidt, M. Tugrul, V. Eguíluz, E. Hernandez Garcia, K. Klemm,
Physical Review E Statistical Nonlinear and Soft Matter Physics 91 (2015).
date_created: 2018-12-11T11:54:31Z
date_published: 2015-02-02T00:00:00Z
date_updated: 2021-01-12T06:53:49Z
day: '02'
department:
- _id: NiBa
doi: 10.1103/PhysRevE.91.022803
external_id:
arxiv:
- '1012.3298'
intvolume: ' 91'
issue: '2'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1012.3298
month: '02'
oa: 1
oa_version: Preprint
publication: Physical Review E Statistical Nonlinear and Soft Matter Physics
publication_status: published
publisher: American Institute of Physics
publist_id: '5213'
quality_controlled: '1'
scopus_import: 1
status: public
title: Anomalous scaling in an age-dependent branching model
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 91
year: '2015'
...
---
_id: '9712'
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
- 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: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Tugrul M, Paixao T, Barton NH, Tkačik G. Other fitness models for comparison
& for interacting TFBSs. 2015. doi:10.1371/journal.pgen.1005639.s001
apa: Tugrul, M., Paixao, T., Barton, N. H., & Tkačik, G. (2015). Other fitness
models for comparison & for interacting TFBSs. Public Library of Science.
https://doi.org/10.1371/journal.pgen.1005639.s001
chicago: Tugrul, Murat, Tiago Paixao, Nicholas H Barton, and Gašper Tkačik. “Other
Fitness Models for Comparison & for Interacting TFBSs.” Public Library of
Science, 2015. https://doi.org/10.1371/journal.pgen.1005639.s001.
ieee: M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Other fitness models for
comparison & for interacting TFBSs.” Public Library of Science, 2015.
ista: Tugrul M, Paixao T, Barton NH, Tkačik G. 2015. Other fitness models for comparison
& for interacting TFBSs, Public Library of Science, 10.1371/journal.pgen.1005639.s001.
mla: Tugrul, Murat, et al. Other Fitness Models for Comparison & for Interacting
TFBSs. Public Library of Science, 2015, doi:10.1371/journal.pgen.1005639.s001.
short: M. Tugrul, T. Paixao, N.H. Barton, G. Tkačik, (2015).
date_created: 2021-07-23T12:00:37Z
date_published: 2015-11-06T00:00:00Z
date_updated: 2023-02-23T10:09:08Z
day: '06'
department:
- _id: NiBa
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pgen.1005639.s001
month: '11'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '1666'
relation: used_in_publication
status: public
status: public
title: Other fitness models for comparison & for interacting TFBSs
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2015'
...
---
_id: '1666'
abstract:
- lang: eng
text: Evolution of gene regulation is crucial for our understanding of the phenotypic
differences between species, populations and individuals. Sequence-specific binding
of transcription factors to the regulatory regions on the DNA is a key regulatory
mechanism that determines gene expression and hence heritable phenotypic variation.
We use a biophysical model for directional selection on gene expression to estimate
the rates of gain and loss of transcription factor binding sites (TFBS) in finite
populations under both point and insertion/deletion mutations. Our results show
that these rates are typically slow for a single TFBS in an isolated DNA region,
unless the selection is extremely strong. These rates decrease drastically with
increasing TFBS length or increasingly specific protein-DNA interactions, making
the evolution of sites longer than ∼ 10 bp unlikely on typical eukaryotic speciation
timescales. Similarly, evolution converges to the stationary distribution of binding
sequences very slowly, making the equilibrium assumption questionable. The availability
of longer regulatory sequences in which multiple binding sites can evolve simultaneously,
the presence of “pre-sites” or partially decayed old sites in the initial sequence,
and biophysical cooperativity between transcription factors, can all facilitate
gain of TFBS and reconcile theoretical calculations with timescales inferred from
comparative genomics.
author:
- first_name: Murat
full_name: Tugrul, Murat
id: 37C323C6-F248-11E8-B48F-1D18A9856A87
last_name: Tugrul
orcid: 0000-0002-8523-0758
- 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: Gasper
full_name: Tkacik, Gasper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkacik
orcid: 0000-0002-6699-1455
citation:
ama: Tugrul M, Paixao T, Barton NH, Tkačik G. Dynamics of transcription factor binding
site evolution. PLoS Genetics. 2015;11(11). doi:10.1371/journal.pgen.1005639
apa: Tugrul, M., Paixao, T., Barton, N. H., & Tkačik, G. (2015). Dynamics of
transcription factor binding site evolution. PLoS Genetics. Public Library
of Science. https://doi.org/10.1371/journal.pgen.1005639
chicago: Tugrul, Murat, Tiago Paixao, Nicholas H Barton, and Gašper Tkačik. “Dynamics
of Transcription Factor Binding Site Evolution.” PLoS Genetics. Public
Library of Science, 2015. https://doi.org/10.1371/journal.pgen.1005639.
ieee: M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Dynamics of transcription
factor binding site evolution,” PLoS Genetics, vol. 11, no. 11. Public
Library of Science, 2015.
ista: Tugrul M, Paixao T, Barton NH, Tkačik G. 2015. Dynamics of transcription factor
binding site evolution. PLoS Genetics. 11(11).
mla: Tugrul, Murat, et al. “Dynamics of Transcription Factor Binding Site Evolution.”
PLoS Genetics, vol. 11, no. 11, Public Library of Science, 2015, doi:10.1371/journal.pgen.1005639.
short: M. Tugrul, T. Paixao, N.H. Barton, G. Tkačik, PLoS Genetics 11 (2015).
date_created: 2018-12-11T11:53:21Z
date_published: 2015-11-06T00:00:00Z
date_updated: 2023-09-07T11:53:49Z
day: '06'
ddc:
- '576'
department:
- _id: NiBa
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pgen.1005639
ec_funded: 1
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oa_version: Published Version
project:
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call_identifier: FP7
grant_number: '250152'
name: Limits to selection in biology and in evolutionary computation
publication: PLoS Genetics
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publisher: Public Library of Science
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title: Dynamics of transcription factor binding site evolution
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...