Cell Selection. In the cell selection approach, a suitable selection pressure is applied, which permits the preferential survival/growth of variant cells only. Some examples of cell selection are selection of cells resistant to various toxins, herbicides, high salt concentration, etc. When the selection pressure allows only the mutant cells to survive or divide, it is called positive selection.

On the other hand, in the case of negative selection, the wild type cells divide normally and, therefore, are killed by a counterselection agent, e.g., 5 BUdR or arsenate; the mutant cells are unable to divide as a result of which they escape the counterselection agent.

These cells are subsequently rescued by removal of the counterselection agent. Negative selection approach is utilized for the isolation of auxotrophic mutants.
The positive selection approach may be further subdivided into four categories:
(i) direct selection,
(ii) rescue method,
(iii) stepwise selection and
(iv) double selection.

The selection pressure, e.g., salt concentration, may be gradually increased from a relatively low level to the cytotoxic level; the resistant clones isolated at each stage are subjected to the higher selection pressure. Such a selection approach is called stepwise selection.

It may often favour gene amplification (which is unstable) or mutations in the organelle DNA. In some cases, it may be feasible to select for survival and/or growth on one hand and some other feature reflecting resistance to the selection pressure on the other; this is called double selection.

An example of double selection is the selection for resistance to streptomycin, which inhibits chlorophyll development in cultured cells. The selection was based on cell survival and colony formation in the presence of streptomycin (one feature) as well as for the development of green colour in these colonies (second feature).