---
_id: '10736'
abstract:
- lang: eng
text: Predicting function from sequence is a central problem of biology. Currently,
this is possible only locally in a narrow mutational neighborhood around a wildtype
sequence rather than globally from any sequence. Using random mutant libraries,
we developed a biophysical model that accounts for multiple features of σ70 binding
bacterial promoters to predict constitutive gene expression levels from any sequence.
We experimentally and theoretically estimated that 10–20% of random sequences
lead to expression and ~80% of non-expressing sequences are one mutation away
from a functional promoter. The potential for generating expression from random
sequences is so pervasive that selection acts against σ70-RNA polymerase binding
sites even within inter-genic, promoter-containing regions. This pervasiveness
of σ70-binding sites implies that emergence of promoters is not the limiting step
in gene regulatory evolution. Ultimately, the inclusion of novel features of promoter
function into a mechanistic model enabled not only more accurate predictions of
gene expression levels, but also identified that promoters evolve more rapidly
than previously thought.
acknowledgement: 'We thank Hande Acar, Nicholas H Barton, Rok Grah, Tiago Paixao,
Maros Pleska, Anna Staron, and Murat Tugrul for insightful comments and input on
the manuscript. This work was supported by: Sir Henry Dale Fellowship jointly funded
by the Wellcome Trust and the Royal Society (grant number 216779/Z/19/Z) to ML;
IPC Grant from IST Austria to ML and SS; European Research Council Funding Programme
7 (2007–2013, grant agreement number 648440) to JPB.'
article_number: e64543
article_processing_charge: No
article_type: original
author:
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
- first_name: Srdjan
full_name: Sarikas, Srdjan
id: 35F0286E-F248-11E8-B48F-1D18A9856A87
last_name: Sarikas
- first_name: Magdalena
full_name: Steinrueck, Magdalena
last_name: Steinrueck
- first_name: David
full_name: Toledo-Aparicio, David
last_name: Toledo-Aparicio
- 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
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Lagator M, Sarikas S, Steinrueck M, et al. Predicting bacterial promoter function
and evolution from random sequences. eLife. 2022;11. doi:10.7554/eLife.64543
apa: Lagator, M., Sarikas, S., Steinrueck, M., Toledo-Aparicio, D., Bollback, J.
P., Guet, C. C., & Tkačik, G. (2022). Predicting bacterial promoter function
and evolution from random sequences. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.64543
chicago: Lagator, Mato, Srdjan Sarikas, Magdalena Steinrueck, David Toledo-Aparicio,
Jonathan P Bollback, Calin C Guet, and Gašper Tkačik. “Predicting Bacterial Promoter
Function and Evolution from Random Sequences.” ELife. eLife Sciences Publications,
2022. https://doi.org/10.7554/eLife.64543.
ieee: M. Lagator et al., “Predicting bacterial promoter function and evolution
from random sequences,” eLife, vol. 11. eLife Sciences Publications, 2022.
ista: Lagator M, Sarikas S, Steinrueck M, Toledo-Aparicio D, Bollback JP, Guet CC,
Tkačik G. 2022. Predicting bacterial promoter function and evolution from random
sequences. eLife. 11, e64543.
mla: Lagator, Mato, et al. “Predicting Bacterial Promoter Function and Evolution
from Random Sequences.” ELife, vol. 11, e64543, eLife Sciences Publications,
2022, doi:10.7554/eLife.64543.
short: M. Lagator, S. Sarikas, M. Steinrueck, D. Toledo-Aparicio, J.P. Bollback,
C.C. Guet, G. Tkačik, ELife 11 (2022).
date_created: 2022-02-06T23:01:32Z
date_published: 2022-01-26T00:00:00Z
date_updated: 2023-08-02T14:09:02Z
day: '26'
ddc:
- '576'
department:
- _id: CaGu
- _id: GaTk
- _id: NiBa
doi: 10.7554/eLife.64543
ec_funded: 1
external_id:
isi:
- '000751104400001'
pmid:
- '35080492'
file:
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creator: cchlebak
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date_updated: 2022-02-07T07:14:09Z
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language:
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project:
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call_identifier: H2020
grant_number: '648440'
name: Selective Barriers to Horizontal Gene Transfer
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Predicting bacterial promoter function and evolution from random sequences
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...
---
_id: '570'
abstract:
- lang: eng
text: 'Most phenotypes are determined by molecular systems composed of specifically
interacting molecules. However, unlike for individual components, little is known
about the distributions of mutational effects of molecular systems as a whole.
We ask how the distribution of mutational effects of a transcriptional regulatory
system differs from the distributions of its components, by first independently,
and then simultaneously, mutating a transcription factor and the associated promoter
it represses. We find that the system distribution exhibits increased phenotypic
variation compared to individual component distributions - an effect arising from
intermolecular epistasis between the transcription factor and its DNA-binding
site. In large part, this epistasis can be qualitatively attributed to the structure
of the transcriptional regulatory system and could therefore be a common feature
in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the
constraints of individual components, thereby increasing phenotypic variation
that selection could act on and facilitating adaptive evolution. '
article_number: e28921
author:
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
- first_name: Srdjan
full_name: Sarikas, Srdjan
id: 35F0286E-F248-11E8-B48F-1D18A9856A87
last_name: Sarikas
- first_name: Hande
full_name: Acar, Hande
id: 2DDF136A-F248-11E8-B48F-1D18A9856A87
last_name: Acar
orcid: 0000-0003-1986-9753
- 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, Sarikas S, Acar H, Bollback JP, Guet CC. Regulatory network structure
determines patterns of intermolecular epistasis. eLife. 2017;6. doi:10.7554/eLife.28921
apa: Lagator, M., Sarikas, S., Acar, H., Bollback, J. P., & Guet, C. C. (2017).
Regulatory network structure determines patterns of intermolecular epistasis.
ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.28921
chicago: Lagator, Mato, Srdjan Sarikas, Hande Acar, Jonathan P Bollback, and Calin
C Guet. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.”
ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.28921.
ieee: M. Lagator, S. Sarikas, H. Acar, J. P. Bollback, and C. C. Guet, “Regulatory
network structure determines patterns of intermolecular epistasis,” eLife,
vol. 6. eLife Sciences Publications, 2017.
ista: Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network
structure determines patterns of intermolecular epistasis. eLife. 6, e28921.
mla: Lagator, Mato, et al. “Regulatory Network Structure Determines Patterns of
Intermolecular Epistasis.” ELife, vol. 6, e28921, eLife Sciences Publications,
2017, doi:10.7554/eLife.28921.
short: M. Lagator, S. Sarikas, H. Acar, J.P. Bollback, C.C. Guet, ELife 6 (2017).
date_created: 2018-12-11T11:47:14Z
date_published: 2017-11-13T00:00:00Z
date_updated: 2021-01-12T08:03:15Z
day: '13'
ddc:
- '576'
department:
- _id: CaGu
- _id: JoBo
- _id: NiBa
doi: 10.7554/eLife.28921
ec_funded: 1
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creator: system
date_created: 2018-12-12T10:14:42Z
date_updated: 2020-07-14T12:47:10Z
file_id: '5096'
file_name: IST-2017-918-v1+1_elife-28921-figures-v3.pdf
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date_updated: 2020-07-14T12:47:10Z
file_id: '5097'
file_name: IST-2017-918-v1+2_elife-28921-v3.pdf
file_size: 1953221
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file_date_updated: 2020-07-14T12:47:10Z
has_accepted_license: '1'
intvolume: ' 6'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _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: '7244'
pubrep_id: '918'
quality_controlled: '1'
scopus_import: 1
status: public
title: Regulatory network structure determines patterns of intermolecular epistasis
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: 6
year: '2017'
...