Lagator, Mato, Sarikas, Srdjan, Steinrueck, Magdalena, Toledo-Aparicio, David, Bollback, Jonathan P 
ORCID: 0000-0002-4624-4612, Guet, Calin C and Tkacik, Gasper
(2022)
Predicting bacterial promoter function and evolution from random sequences.
ELIFE, 11.
e64543-.
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 σ<sup>70</sup> 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 σ<sup>70</sup>-RNA polymerase binding sites even within inter-genic, promoter-containing regions. This pervasiveness of σ<sup>70</sup>-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Escherichia coli, Evolution, Molecular, Gene Expression, Mutation, Genome, Bacterial, Models, Theoretical, Promoter Regions, Genetic |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 19 May 2022 09:32 |
| Last Modified: | 20 Jan 2024 22:32 |
| DOI: | 10.7554/eLife.64543 |
| Open Access URL: | https://doi.org/10.7554/eLife.64543 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3155132 |
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