FIGURE 1.

Statistical epistasis. (A) When considering the penetrance of a given phenotype as the percentage of animals expressing this phenotype at a given “significative” level, genetic interactions (GIs) are usually identified using the additive model. Considering the phenotype of wild-type (wt) animals, close to zero, the expected phenotype of the double mutant AB corresponds to the sum of the phenotypes of mutant A and B. An aggravating GI between A and B is then identified if the phenotype of AB is significantly higher than the expected. An Alleviating GI is identified if the phenotype of AB is significantly lower than expected. A suppressive interaction is identified if the phenotype of AB is lower than the single mutant with the highest penetrance. When considering two mutants C and D with no observable phenotype, a synthetic interaction is identified if the double mutant CD expresses a significant phenotype. (B) When fitness is measured as a phenotype, the wt animals present high fitness rate, the expected phenotype of the double mutant AB is calculated using the multiplicative phenotype (it could also be the Log or Min) as the product of the fitness level of A and B. An aggravating interaction is then identified if AB is significantly lower than expected. Alleviating is identified if the fitness of AB is significantly higher than expected. Suppressive interaction is identified or if the double mutant is more viable than the sickest single mutants. A synthetic interaction is identified if the double mutant presents a significant fitness defect while the two single mutants are fit.