Protein abundance affects the evolution of protein genotypes, but we do not know how it affects the evolution of protein phenotypes. Here we investigate the role of protein abundance in the evolvability of green fluorescent protein (GFP) towards the novel phenotype of cyan fluorescence. We evolve GFP in E. coli through multiple cycles of mutation and selection and show that low GFP expression facilitates the evolution of cyan fluorescence. A computational model whose predictions we test experimentally helps explain why: lowly expressed proteins are under stronger selection for proper folding, which facilitates their evolvability on short evolutionary time scales. The reason is that high fluorescence can be achieved by either few proteins that fold well or by many proteins that fold less well. In other words, we observe a synergy between a protein’s scarcity and its stability. Because many proteins meet the essential requirements for this scarcity–stability synergy, it may be a widespread mechanism by which low expression helps proteins evolve new phenotypes and functions.

蛋白质丰度影响蛋白质基因型的进化，但我们不知道它如何影响蛋白质表型的进化。在这里，我们研究了蛋白质丰度在绿色荧光蛋白 (GFP) 向青色荧光新表型的进化能力中的作用。我们在大肠杆菌中进化 GFP通过多次突变和选择循环，表明低 GFP 表达促进了青色荧光的演变。我们通过实验测试其预测的计算模型有助于解释原因：低表达的蛋白质在正确折叠方面受到更强的选择，这促进了它们在短进化时间尺度上的进化能力。原因是高荧光可以通过折叠良好的少数蛋白质或许多折叠不太好的蛋白质来实现。换句话说，我们观察到蛋白质稀缺性和稳定性之间的协同作用。因为许多蛋白质满足这种稀缺-稳定协同作用的基本要求，它可能是一种广泛的机制，低表达可以帮助蛋白质进化出新的表型和功能。