Neutral drift upon threshold-like selection promotes variation in antibiotic resistance phenotype.

Area of Science:

• Evolutionary Biology
• Microbial Genetics
• Biochemistry

Background:

• Heritable phenotypic variation is key to population adaptation and evolution.
• Understanding genotype-phenotype-environment links is crucial but challenging.
• Existing models struggle to explain the emergence and maintenance of widespread phenotypic variation.

Purpose of the Study:

• To establish a controlled experimental system for studying genotype-phenotype relationships.
• To investigate the conditions promoting phenotypic variation during experimental evolution.
• To explore the evolution of antibiotic resistance in VIM-2 β-lactamase populations.

Main Methods:

• Long-term experimental evolution of VIM-2 β-lactamase.
• Controlled environmental conditions with low antibiotic concentrations.
• Analysis of genotype-phenotype relationships and fitness landscapes.

Main Results:

• Static environments with low antibiotic concentrations promote and maintain significant phenotypic variation.
• Evolved VIM-2 variants showed over 100-fold increased antibiotic resistance.
• A fitness-based model explained the emergence of standing phenotypic variation.

Conclusions:

• Phenotypic variation can emerge and be maintained under static, low-selection conditions.
• The VIM-2 system provides a tractable model for studying population-level evolvability.
• This research offers insights into the mechanisms driving adaptive evolution and resistance.