Evolvability as a function of purifying selection in TEM-1 β-lactamase

Area of Science:

• Evolutionary biology
• Biochemistry
• Molecular evolution

Background:

• Evolvability, the capacity for beneficial heritable variation, is crucial for biological systems.
• The origins and environmental modulation of evolvability remain underexplored.

Purpose of the Study:

• To systematically examine the origins and environmental modulation of evolvability.
• To analyze the fitness effects of mutations in TEM-1 β-lactamase under different selection pressures.

Main Methods:

• Analysis of all single mutations (4,997 variants) in TEM-1 β-lactamase.
• Selection for wild-type function (ampicillin resistance) and a new function (cefotaxime resistance).
• Assessment of mutation tolerance and its dependence on selection strength and enzyme activity.

Main Results:

• Mutation tolerance in TEM-1 β-lactamase is bimodal and contingent on purifying selection strength.
• A steep, non-linear relationship exists between ampicillin resistance, biochemical activity, and fitness.
• New functions (cefotaxime resistance) arise from mutations that vary in effect based on ampicillin levels, highlighting selection's role.

Conclusions:

• Evolvability is controlled by an excess of enzymatic activity relative to selection strength.
• Fluctuating environments may favor the selection of high-activity enzymes, enhancing evolvability.
• The capacity to evolve new functions is intrinsically linked to environmental selection pressures.