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Predicting bacterial promoter function and evolution from random sequences
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DOI：10.7554/eLife.64543.png)
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Abstract
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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 sigma(70) 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 similar to 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 sigma(70)-RNA polymerase binding sites even within intergenic, promoter-containing regions. This pervasiveness of sigma(70)-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.
Keywords:
TRANSCRIPTIONAL REGULATION
ESCHERICHIA-COLI
GENE-EXPRESSION
BINDING
MECHANISMS
NUMBERS
FITNESS
PROTEIN
MODEL
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