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Updated: May 8, 2026
11:34
Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
The evolution of complex gene regulation by low-specificity binding sites.
Alexander J Stewart1, Joshua B Plotkin
1Department of Biology, University of Pennsylvania, Philadelphia, PA, USA.
Proceedings. Biological Sciences
|August 16, 2013
Summary
Complex gene regulatory modules evolve to use less specific binding motifs as they grow larger. This finding explains trends in gene regulation across species, from yeast to humans.
Area of Science:
- Genetics
- Evolutionary Biology
- Systems Biology
Background:
- Gene regulation varies significantly within and across species.
- Transcriptional regulation often relies on modules of multiple transcription factor binding sites.
- Understanding the evolution of these regulatory modules is crucial.
Purpose of the Study:
- To investigate the evolutionary dynamics of transcriptional regulatory modules under natural selection.
- To determine how module size influences the specificity of transcription factor binding motifs.
Main Methods:
- Development of a population-genetic model.
- Analysis of regulatory module evolution.
- Comparison of model predictions with empirical data.
Main Results:
- Larger regulatory modules necessitate less specific binding motifs on average compared to smaller modules.
- This effect is independent of the specific binding logic selected for.
- Stabilizing selection struggles to maintain highly specific sites in extensive regulatory modules.
Conclusions:
- The study provides a general principle governing the evolution of regulatory module complexity.
- Findings explain observed relationships between module size and motif specificity in Saccharomyces cerevisiae.
- Results offer insights into regulatory network evolution across diverse taxa, including prokaryotes and eukaryotes.
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