Functional origins of fitness effect-sizes of compensatory mutations in the DNA bacteriophage phiX174

The effect-sizes of 52 compensatory mutations affecting nine different deleterious mutations in the major capsid and spike proteins of the DNA bacteriophage phiX174 are measured. An examination of the relative contributions of specific biochemical properties to variation in fitness effect-size revealed that the area and charge of amino acids have a major influence, suggesting that the complexity of the amino acid phenotype is simplified by selection into a reduced number of phenotypic components.