Predicting bacterial promoter function and evolution from random sequences

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.

Download
OA 2022_ELife_Lagator.pdf 5.60 MB

Journal Article | Published | English

Scopus indexed
Author
Abstract
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.
Publishing Year
Date Published
2022-01-26
Journal Title
eLife
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.
Volume
11
Article Number
e64543
eISSN
IST-REx-ID

Cite this

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
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
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.
M. Lagator et al., “Predicting bacterial promoter function and evolution from random sequences,” eLife, vol. 11. eLife Sciences Publications, 2022.
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.
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.
All files available under the following license(s):
Creative Commons Attribution 4.0 International Public License (CC-BY 4.0):
Main File(s)
File Name
Access Level
OA Open Access
Date Uploaded
2022-02-07
MD5 Checksum
decdcdf600ff51e9a9703b49ca114170


Export

Marked Publications

Open Data ISTA Research Explorer

Web of Science

View record in Web of Science®

Sources

PMID: 35080492
PubMed | Europe PMC

Search this title in

Google Scholar