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Irrelevant Stimuli and Action Control: Analyzing the Influence of Ignored Stimuli via the Distractor-Response Binding Paradigm
Published on: May 14, 2014
Direct demonstration of an adaptive constraint
Stephen P Miller1, Mark Lunzer, Antony M Dean
1BioTechnology Institute, University of Minnesota, St. Paul, MN 55108, USA.
Science (New York, N.Y.)
|October 21, 2006
Summary
Directed evolution of beta-isopropylmalate dehydrogenase (IMDH) reveals that enzyme constraints, like cofactor inhibition, shape adaptive evolution. These limitations explain why engineered enzymes evolve lower affinities for nicotinamide adenine dinucleotide phosphate (NADP).
Area of Science:
- Biochemistry
- Evolutionary Biology
- Enzyme Engineering
Background:
- The role of evolutionary constraints in shaping adaptation remains incompletely understood.
- Beta-isopropylmalate dehydrogenase (IMDH) naturally uses nicotinamide adenine dinucleotide (NAD) but can be engineered for nicotinamide adenine dinucleotide phosphate (NADP) specificity.
- Understanding enzyme evolution requires examining adaptive landscapes and inherent limitations.
Purpose of the Study:
- To investigate the impact of enzymatic constraints on the adaptive evolution of engineered IMDH.
- To determine if observed evolutionary outcomes align with predictions from theoretical adaptive landscapes.
- To elucidate the interplay between selection and constraints in enzyme evolution.
Main Methods:
- Directed evolution was employed to alter the coenzyme specificity of an engineered IMDH from NAD to NADP.
- Mutant enzyme affinities for NADP and NADPH were measured.
- The observed evolutionary trajectory was analyzed against a model incorporating known enzymatic constraints.
Main Results:
- Engineered IMDH consistently evolved lower affinities for NADP, a correlated response to selection for reduced NADPH inhibition.
- This outcome is consistent with an adaptive landscape limited by maximum turnover rate (kcat), NADP/NADPH affinity correlations, and NAD/NADP usage trade-offs.
- High intracellular NADPH levels and protein synthesis costs further reinforced NAD usage.
Conclusions:
- Evolutionary constraints significantly influence the direction and outcome of adaptive evolution.
- Adaptive landscapes, defined by enzymatic limitations, are crucial for understanding enzyme evolution.
- Selective pressures interact with inherent constraints to produce predictable evolutionary patterns.
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