Effect of expression level on the evolvability of protein

We studied the evolvability of highly and lowly expressed proteins using green fluorescent protein (GFP) as a model. To this end, we subjected the highly and lowly expressed gfp populations to directed evolution and selected for the expression of new phenotype of cyan fluorescence. Our experiments show that the lowly expressed proteins are more evolvable. The model based on our experiment predicts that this difference in evolvability arises due to the synergy between stability and scarcity of the proteins. We experimentally confirm the prediction to show that highly expressed proteins harbour more destabilizing mutations which hampers their evolvability.