---
_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). <i>Evolution of transcriptional regulatory sequences</i>.
    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. <i>Evolution of Transcriptional Regulatory Sequences</i>. 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: 2025-05-28T11:57:04Z
day: '01'
ddc:
- '576'
degree_awarded: PhD
department:
- _id: NiBa
file:
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has_accepted_license: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: '89'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '6229'
related_material:
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    status: public
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    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:<a href="https://doi.org/10.15479/AT:ISTA:43">10.15479/AT:ISTA:43</a>
  apa: Tugrul, M. (2016). Experimental Data for Binding Site Evolution of Bacterial
    RNA Polymerase. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:43">https://doi.org/10.15479/AT:ISTA:43</a>
  chicago: Tugrul, Murat. “Experimental Data for Binding Site Evolution of Bacterial
    RNA Polymerase.” Institute of Science and Technology Austria, 2016. <a href="https://doi.org/10.15479/AT:ISTA:43">https://doi.org/10.15479/AT:ISTA:43</a>.
  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, <a href="https://doi.org/10.15479/AT:ISTA:43">10.15479/AT:ISTA:43</a>.
  mla: Tugrul, Murat. <i>Experimental Data for Binding Site Evolution of Bacterial
    RNA Polymerase</i>. Institute of Science and Technology Austria, 2016, doi:<a
    href="https://doi.org/10.15479/AT:ISTA:43">10.15479/AT:ISTA:43</a>.
  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
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  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:
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    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: '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. <i>PLoS Genetics</i>. 2015;11(11). doi:<a href="https://doi.org/10.1371/journal.pgen.1005639">10.1371/journal.pgen.1005639</a>
  apa: Tugrul, M., Paixao, T., Barton, N. H., &#38; Tkačik, G. (2015). Dynamics of
    transcription factor binding site evolution. <i>PLoS Genetics</i>. Public Library
    of Science. <a href="https://doi.org/10.1371/journal.pgen.1005639">https://doi.org/10.1371/journal.pgen.1005639</a>
  chicago: Tugrul, Murat, Tiago Paixao, Nicholas H Barton, and Gašper Tkačik. “Dynamics
    of Transcription Factor Binding Site Evolution.” <i>PLoS Genetics</i>. Public
    Library of Science, 2015. <a href="https://doi.org/10.1371/journal.pgen.1005639">https://doi.org/10.1371/journal.pgen.1005639</a>.
  ieee: M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Dynamics of transcription
    factor binding site evolution,” <i>PLoS Genetics</i>, 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.”
    <i>PLoS Genetics</i>, vol. 11, no. 11, Public Library of Science, 2015, doi:<a
    href="https://doi.org/10.1371/journal.pgen.1005639">10.1371/journal.pgen.1005639</a>.
  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
file:
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  date_updated: 2020-07-14T12:45:10Z
  file_id: '4657'
  file_name: IST-2016-463-v1+1_journal.pgen.1005639.pdf
  file_size: 2580778
  relation: main_file
file_date_updated: 2020-07-14T12:45:10Z
has_accepted_license: '1'
intvolume: '        11'
issue: '11'
language:
- iso: eng
month: '11'
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
publication: PLoS Genetics
publication_status: published
publisher: Public Library of Science
publist_id: '5483'
pubrep_id: '463'
quality_controlled: '1'
related_material:
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  - id: '9712'
    relation: research_data
    status: public
  - id: '1131'
    relation: dissertation_contains
    status: public
scopus_import: 1
status: public
title: Dynamics of transcription factor binding site evolution
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 11
year: '2015'
...
---
_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
arxiv: 1
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. <i>Physical Review E Statistical
    Nonlinear and Soft Matter Physics</i>. 2015;91(2). doi:<a href="https://doi.org/10.1103/PhysRevE.91.022803">10.1103/PhysRevE.91.022803</a>
  apa: Keller-Schmidt, S., Tugrul, M., Eguíluz, V., Hernandez Garcia, E., &#38; Klemm,
    K. (2015). Anomalous scaling in an age-dependent branching model. <i>Physical
    Review E Statistical Nonlinear and Soft Matter Physics</i>. American Institute
    of Physics. <a href="https://doi.org/10.1103/PhysRevE.91.022803">https://doi.org/10.1103/PhysRevE.91.022803</a>
  chicago: Keller-Schmidt, Stephanie, Murat Tugrul, Víctor Eguíluz, Emilio Hernandez
    Garcia, and Konstantin Klemm. “Anomalous Scaling in an Age-Dependent Branching
    Model.” <i>Physical Review E Statistical Nonlinear and Soft Matter Physics</i>.
    American Institute of Physics, 2015. <a href="https://doi.org/10.1103/PhysRevE.91.022803">https://doi.org/10.1103/PhysRevE.91.022803</a>.
  ieee: S. Keller-Schmidt, M. Tugrul, V. Eguíluz, E. Hernandez Garcia, and K. Klemm,
    “Anomalous scaling in an age-dependent branching model,” <i>Physical Review E
    Statistical Nonlinear and Soft Matter Physics</i>, 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.” <i>Physical Review E Statistical Nonlinear and Soft Matter Physics</i>,
    vol. 91, no. 2, 022803, American Institute of Physics, 2015, doi:<a href="https://doi.org/10.1103/PhysRevE.91.022803">10.1103/PhysRevE.91.022803</a>.
  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
    &#38; for interacting TFBSs. 2015. doi:<a href="https://doi.org/10.1371/journal.pgen.1005639.s001">10.1371/journal.pgen.1005639.s001</a>
  apa: Tugrul, M., Paixao, T., Barton, N. H., &#38; Tkačik, G. (2015). Other fitness
    models for comparison &#38; for interacting TFBSs. Public Library of Science.
    <a href="https://doi.org/10.1371/journal.pgen.1005639.s001">https://doi.org/10.1371/journal.pgen.1005639.s001</a>
  chicago: Tugrul, Murat, Tiago Paixao, Nicholas H Barton, and Gašper Tkačik. “Other
    Fitness Models for Comparison &#38; for Interacting TFBSs.” Public Library of
    Science, 2015. <a href="https://doi.org/10.1371/journal.pgen.1005639.s001">https://doi.org/10.1371/journal.pgen.1005639.s001</a>.
  ieee: M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Other fitness models for
    comparison &#38; for interacting TFBSs.” Public Library of Science, 2015.
  ista: Tugrul M, Paixao T, Barton NH, Tkačik G. 2015. Other fitness models for comparison
    &#38; for interacting TFBSs, Public Library of Science, <a href="https://doi.org/10.1371/journal.pgen.1005639.s001">10.1371/journal.pgen.1005639.s001</a>.
  mla: Tugrul, Murat, et al. <i>Other Fitness Models for Comparison &#38; for Interacting
    TFBSs</i>. Public Library of Science, 2015, doi:<a href="https://doi.org/10.1371/journal.pgen.1005639.s001">10.1371/journal.pgen.1005639.s001</a>.
  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: 2025-05-28T11:57:04Z
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:
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  - 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'
...