A central question in biology is how changes on the genotype level manifest themselves on the level of the phenotype. In other words, if a mutation occurs in a gene – what happens? A potent metaphor is the fitness landscape, an abstract representation of how genetic changes affect what happens to the organism. In this study, we selected the Green Fluorescent Protein (GFP), which normally fluoresces in green, as a model to study the question of how mutations would affect its function of fluorescent.
We created over 50,000 thousand genotypes of GFP proteins with different number of mutations and individually accessed their levels of fluorescence. We found that mutations do not contribute independently to GFP fluorescence. The main mechanism is best described as the poor get poorer, with a genotype carrying several mutations showing a level of fluorescence much lower than would be expected if those mutations were making their contribution independently of each other. The results of our study present a model for the prediction of how multiple mutations can collectively affect the function of a protein. Perhaps similar studies can illuminate the mechanism of collective action of mutation on more complex genotypes.