Predicting bacterial promoter function and evolution from random sequences

eLife

Jonathan P Bollback¹  Gašper Tkačik²  Calin C Guet²  Magdalena Steinrueck²  David Toledo-Aparicio²  Srdjan Sarikas³  Mato Lagator⁴ 

[1] Institute of Integrative Biology, Functional and Comparative Genomics, University of Liverpool, Liverpool, United Kingdom;Institute of Science and Technology Austria, Klosterneuburg, Austria;Institute of Science and Technology Austria, Klosterneuburg, Austria;Center for Physiology and Pharmacology, Medical University of Vienna, Klosterneuburg, Austria;School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom;Institute of Science and Technology Austria, Klosterneuburg, Austria;

关键词: gene regulation;    RNA polymerase;    genotype-phenotype map;    adaptive evolution;    promoter;    E. coli;   

DOI  :  10.7554/eLife.64543

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY