Speaker
Description
As genetic analysis increasingly moves from one dimension (genotype-phenotype) to the second dimension (interactions between genotype-phenotype pairs) and even third dimension (additional mutations modifying the two-gene interactions), a better understanding of the complex effects is required to use this powerful tool intelligently. Of the four general types of genetic interactions (epistasis, additivity, synergy and compensation), synergy creates the most excitement — perhaps because it is both rare and unexpected, but also because of its dark, mysterious extreme. Indeed, the ultimate synergy yields synthetic lethality, or colethality — a combination of two otherwise modest-effect mutations that proves completely dead. Colethality is typically attributed to “inactivation of two redundant activities both contributing to the same essential function” — but it is rarely the case in real life. The major explanation of colethal combinations is “potentiation”, when one genetic defect greatly potentiates the problems of the second defect. We call these gene pairs “the avoidance-repair couples” around an essential cellular molecule or structure. And there is also a third explanation, “loss-of-support”, due to the complications coming from colethals in which one mutation is a hypomorph of an essential gene. One way to distinguish between the three explanation is via suppressors, which takes our genetic analysis to the third dimension.