---
_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.
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: 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: 2025-09-23T08:31:15Z
day: '06'
ddc:
- '576'
department:
- _id: NiBa
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pgen.1005639
ec_funded: 1
external_id:
  isi:
  - '000366179000022'
file:
- access_level: open_access
  checksum: a4e72fca5ccf40ddacf4d08c8e46b554
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:07:58Z
  date_updated: 2020-07-14T12:45:10Z
  file_id: '4657'
  file_name: IST-2016-463-v1+1_journal.pgen.1005639.pdf
  file_size: 2580778
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file_date_updated: 2020-07-14T12:45:10Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
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:
  record:
  - 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 11
year: '2015'
...