Comparison of the theoretical and real-world evolutionary potential of a genetic circuit

Razo-Mejia, M., Boedicker, J. Q., Jones, D., Deluna, A., Kinney, J. B., Phillips, R. (April 2014) Comparison of the theoretical and real-world evolutionary potential of a genetic circuit. Physical Biology, 11 (2). ISSN 14783975

DOI: 10.1088/1478-3975/11/2/026005


With the development of next-generation sequencing technologies, many large scale experimental efforts aim to map genotypic variability among individuals. This natural variability in populations fuels many fundamental biological processes, ranging from evolutionary adaptation and speciation to the spread of genetic diseases and drug resistance. An interesting and important component of this variability is present within the regulatory regions of genes. As these regions evolve, accumulated mutations lead to modulation of gene expression, which may have consequences for the phenotype. A simple model system where the link between genetic variability, gene regulation and function can be studied in detail is missing. In this article we develop a model to explore how the sequence of the wild-type lac promoter dictates the fold-change in gene expression. The model combines single-base pair resolution maps of transcription factor and RNA polymerase binding energies with a comprehensive thermodynamic model of gene regulation. The model was validated by predicting and then measuring the variability of lac operon regulation in a collection of natural isolates. We then implement the model to analyze the sensitivity of the promoter sequence to the regulatory output, and predict the potential for regulation to evolve due to point mutations in the promoter region.

Item Type: Paper
Subjects: bioinformatics
bioinformatics > computational biology
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL labs > Kinney lab
CSHL Cancer Center Shared Resources > DNA Sequencing Service
Depositing User: Matt Covey
Date: 20 April 2014
Date Deposited: 02 May 2014 19:32
Last Modified: 18 Jan 2017 16:57
PMCID: PMC4051709
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