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Updated: Jan 24, 2026
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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
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A major role for noncoding regulatory mutations in the evolution of enzyme activity
David W Loehlin1,2,3, Jesse R Ames4, Kathy Vaccaro2,3,5
1Biology Department, Williams College, Williamstown, MA 01267; dwl1@williams.edu carrolls@hhmi.org.
Summary
Regulatory mutations, not protein sequence changes, primarily drive quantitative evolution of alcohol dehydrogenase activity in Drosophila. These genetic shifts in gene regulation significantly impact enzyme levels and organism fitness.
Area of Science:
- Evolutionary biology
- Molecular evolution
- Genetics
Background:
- Quantitative changes in protein activity are common but poorly understood.
- Evolution of enzyme activity can stem from altered protein function or expression levels.
Purpose of the Study:
- To identify genetic mechanisms behind quantitative evolution of alcohol dehydrogenase (Adh) activity.
- To differentiate contributions of coding vs. noncoding mutations to Adh activity differences.
Main Methods:
- Used recombinant Adh transgenes in Drosophila to map functional divergence.
- Analyzed differences in Adh enzyme activity between and within Drosophila species.
Main Results:
- Amino acid substitutions explained only a small fraction (0-25%) of Adh activity differences.
- Noncoding substitutions in regulatory regions (promoter, enhancers, UTRs) drove most activity changes.
- Parallel evolution of a transcriptional initiator element suggests core promoter importance.
Conclusions:
- Regulatory mutations are likely the main drivers of quantitative protein activity evolution.
- Both regulatory and coding changes influence fitness (ethanol resistance).
- Highlights the significance of regulatory evolution, often overlooked in protein evolution studies.
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