A mammalian cell line was cultured for many generations in the presence of methotrexate, whose concentration in the culture medium was steadily increased. After maximum resistance to methotrexate had been achieved, the cells were transferred to drug-free medium for many more generations. At the beginning of the experiment, dihydrofolate reductase represented 0.1% of the soluble protein in the cell; at maximum resistance it was 10.0%; and at the conclusion of the experiment, 1.5%. Describe in qualitative terms the processes involved in generating maximum resistance.