---
_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: Steinrück, Magdalena
id: 2C023F40-F248-11E8-B48F-1D18A9856A87
last_name: Steinrück
orcid: 0000-0003-1229-9719
- 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, Steinrück 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., Steinrück, 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 Steinrück, 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, Steinrück 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. Steinrück, D. Toledo-Aparicio, J.P. Bollback,
C.C. Guet, G. Tkačik, ELife 11 (2022).
corr_author: '1'
date_created: 2022-02-06T23:01:32Z
date_published: 2022-01-26T00:00:00Z
date_updated: 2025-03-31T16:00:23Z
day: '26'
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department:
- _id: CaGu
- _id: GaTk
- _id: NiBa
doi: 10.7554/eLife.64543
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call_identifier: H2020
grant_number: '648440'
name: Selective Barriers to Horizontal Gene Transfer
publication: eLife
publication_identifier:
eissn:
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publication_status: published
publisher: eLife Sciences Publications
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title: Predicting bacterial promoter function and evolution from random sequences
tmp:
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...
---
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abstract:
- lang: eng
text: Expression of genes is a fundamental molecular phenotype that is subject to
evolution by different types of mutations. Both the rate and the effect of mutations
may depend on the DNA sequence context of a particular gene or a particular promoter
sequence. In this thesis I investigate the nature of this dependence using simple
genetic systems in Escherichia coli. With these systems I explore the evolution
of constitutive gene expression from random starting sequences at different loci
on the chromosome and at different locations in sequence space. First, I dissect
chromosomal neighborhood effects that underlie locus-dependent differences in
the potential of a gene under selection to become more highly expressed. Next,
I find that the effects of point mutations in promoter sequences are dependent
on sequence context, and that an existing energy matrix model performs poorly
in predicting relative expression of unrelated sequences. Finally, I show that
a substantial fraction of random sequences contain functional promoters and I
present an extended thermodynamic model that predicts promoter strength in full
sequence space. Taken together, these results provide new insights and guides
on how to integrate information on sequence context to improve our qualitative
and quantitative understanding of bacterial gene expression, with implications
for rapid evolution of drug resistance, de novo evolution of genes, and horizontal
gene transfer.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Magdalena
full_name: Steinrück, Magdalena
id: 2C023F40-F248-11E8-B48F-1D18A9856A87
last_name: Steinrück
orcid: 0000-0003-1229-9719
citation:
ama: Steinrück M. The influence of sequence context on the evolution of bacterial
gene expression. 2018. doi:10.15479/AT:ISTA:th1059
apa: Steinrück, M. (2018). The influence of sequence context on the evolution
of bacterial gene expression. Institute of Science and Technology Austria.
https://doi.org/10.15479/AT:ISTA:th1059
chicago: Steinrück, Magdalena. “The Influence of Sequence Context on the Evolution
of Bacterial Gene Expression.” Institute of Science and Technology Austria, 2018.
https://doi.org/10.15479/AT:ISTA:th1059.
ieee: M. Steinrück, “The influence of sequence context on the evolution of bacterial
gene expression,” Institute of Science and Technology Austria, 2018.
ista: Steinrück M. 2018. The influence of sequence context on the evolution of bacterial
gene expression. Institute of Science and Technology Austria.
mla: Steinrück, Magdalena. The Influence of Sequence Context on the Evolution
of Bacterial Gene Expression. Institute of Science and Technology Austria,
2018, doi:10.15479/AT:ISTA:th1059.
short: M. Steinrück, The Influence of Sequence Context on the Evolution of Bacterial
Gene Expression, Institute of Science and Technology Austria, 2018.
corr_author: '1'
date_created: 2018-12-11T11:44:14Z
date_published: 2018-10-30T00:00:00Z
date_updated: 2026-04-08T14:15:35Z
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status: public
supervisor:
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full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
title: The influence of sequence context on the evolution of bacterial gene expression
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2018'
...
---
_id: '5564'
abstract:
- lang: eng
text: Compressed Fastq files with whole-genome sequencing data of IS-wt strain D
and clones from four evolved populations (A11, C08, C10, D08). Information on
this data collection is available in the Methods Section of the primary publication.
article_processing_charge: No
author:
- first_name: Magdalena
full_name: Steinrück, Magdalena
id: 2C023F40-F248-11E8-B48F-1D18A9856A87
last_name: Steinrück
orcid: 0000-0003-1229-9719
- 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: Steinrück M, Guet CC. Fastq files for “Complex chromosomal neighborhood effects
determine the adaptive potential of a gene under selection.” 2017. doi:10.15479/AT:ISTA:65
apa: Steinrück, M., & Guet, C. C. (2017). Fastq files for “Complex chromosomal
neighborhood effects determine the adaptive potential of a gene under selection.”
Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:65
chicago: Steinrück, Magdalena, and Calin C Guet. “Fastq Files for ‘Complex Chromosomal
Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.’”
Institute of Science and Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:65.
ieee: M. Steinrück and C. C. Guet, “Fastq files for ‘Complex chromosomal neighborhood
effects determine the adaptive potential of a gene under selection.’” Institute
of Science and Technology Austria, 2017.
ista: Steinrück M, Guet CC. 2017. Fastq files for ‘Complex chromosomal neighborhood
effects determine the adaptive potential of a gene under selection’, Institute
of Science and Technology Austria, 10.15479/AT:ISTA:65.
mla: Steinrück, Magdalena, and Calin C. Guet. Fastq Files for “Complex Chromosomal
Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.”
Institute of Science and Technology Austria, 2017, doi:10.15479/AT:ISTA:65.
short: M. Steinrück, C.C. Guet, (2017).
datarep_id: '65'
date_created: 2018-12-12T12:31:33Z
date_published: 2017-04-11T00:00:00Z
date_updated: 2025-09-10T11:06:52Z
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ddc:
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department:
- _id: CaGu
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title: Fastq files for "Complex chromosomal neighborhood effects determine the adaptive
potential of a gene under selection"
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...
---
_id: '704'
abstract:
- lang: eng
text: 'How the organization of genes on a chromosome shapes adaptation is essential
for understanding evolutionary paths. Here, we investigate how adaptation to rapidly
increasing levels of antibiotic depends on the chromosomal neighborhood of a drug-resistance
gene inserted at different positions of the Escherichia coli chromosome. Using
a dual-fluorescence reporter that allows us to distinguish gene amplifications
from other up-mutations, we track in real-time adaptive changes in expression
of the drug-resistance gene. We find that the relative contribution of several
mutation types differs systematically between loci due to properties of neighboring
genes: essentiality, expression, orientation, termination, and presence of duplicates.
These properties determine rate and fitness effects of gene amplification, deletions,
and mutations compromising transcriptional termination. Thus, the adaptive potential
of a gene under selection is a system-property with a complex genetic basis that
is specific for each chromosomal locus, and it can be inferred from detailed functional
and genomic data.'
article_number: e25100
article_processing_charge: No
author:
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full_name: Steinrück, Magdalena
id: 2C023F40-F248-11E8-B48F-1D18A9856A87
last_name: Steinrück
orcid: 0000-0003-1229-9719
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
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citation:
ama: Steinrück M, Guet CC. Complex chromosomal neighborhood effects determine the
adaptive potential of a gene under selection. eLife. 2017;6. doi:10.7554/eLife.25100
apa: Steinrück, M., & Guet, C. C. (2017). Complex chromosomal neighborhood effects
determine the adaptive potential of a gene under selection. ELife. eLife
Sciences Publications. https://doi.org/10.7554/eLife.25100
chicago: Steinrück, Magdalena, and Calin C Guet. “Complex Chromosomal Neighborhood
Effects Determine the Adaptive Potential of a Gene under Selection.” ELife.
eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25100.
ieee: M. Steinrück and C. C. Guet, “Complex chromosomal neighborhood effects determine
the adaptive potential of a gene under selection,” eLife, vol. 6. eLife
Sciences Publications, 2017.
ista: Steinrück M, Guet CC. 2017. Complex chromosomal neighborhood effects determine
the adaptive potential of a gene under selection. eLife. 6, e25100.
mla: Steinrück, Magdalena, and Calin C. Guet. “Complex Chromosomal Neighborhood
Effects Determine the Adaptive Potential of a Gene under Selection.” ELife,
vol. 6, e25100, eLife Sciences Publications, 2017, doi:10.7554/eLife.25100.
short: M. Steinrück, C.C. Guet, ELife 6 (2017).
corr_author: '1'
date_created: 2018-12-11T11:48:01Z
date_published: 2017-07-25T00:00:00Z
date_updated: 2026-08-29T22:30:13Z
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title: Complex chromosomal neighborhood effects determine the adaptive potential of
a gene under selection
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...