---
_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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language:
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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:
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'
...