In this cartoon, a common ancestor bearing the Mlh1 Gly 761 and Pms1 Arg 818/822 alleles can sustain mutations, neutral or beneficial, that give rise to the derived S288c (purple, Asp 761, Arg 818/822) and SK1 (green, Gly 761, Lys 818/822) group strains. Mating between the derived strains can yield an allele combination (Mlh1 Asp 761, Pms1 Lys 818/822) that had not been selected for function, leading to a negative epistatic interaction and a mutator phenotype. Sequencing analysis of a 32-kb region in the derived groups provided evidence for recombination between the two, supporting the idea that these two groups can meet in nature, exchange genetic information, and form a hybrid mutator [22].