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In a single-mutant strain, mutations may occur in other genes for resistance; and when two mutant genes are together in one individual (double mutants) their effect is cumulative. Moreover, it happens that the resistance of a double mutant is higher than the sum of resistances of two single mutants. If a third gene for resistance, a fourth, etc., mutate in the same line, the combined effect of all these mutations is a high degree of resistance or complete resistance.

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