Synthetic enhancement

(a) Sturtevant’s cross ident—ifying synthetic lethality 9.— T The dominant allele F 9 en" K'E" dB‘LIneki/IeflK-pn) in ' - n + combination wrth loss a-ll die ofprune(pn) function = Y chromosome results in lethality (b) Possible mechanisms for synthetic enhancement Between-pathway interactions Pathway A Pathway B ® \/ Essential biological function If two pathways both perform the same essential function, mutation of either alone may be inconsequential, but mutations in ‘ both results in a loss of the essential function. Withinpafltway interactions C1 wild type c1 mutant Cl wild type c1 mutant C2 wild type C2 wild type c2 mutant c2 mutant Full : Reduced ; Reduced Insufficient l pathway ; pathway ; pathway pathway activity activity activity activity Essential function Wild type Viable Viable Lethal ‘ Partial loss-of—function mutations in C1 or C2 alone reduce functions, but organism is still viable, However, if both components ‘ are mutated, the pathway may become nonfunctional.