Local regulation of homeostasis favors chromosomal instability.

Tissues of long-lived multicellular organisms have to maintain a constant number of functioning cells for many years. This process is called homeostasis. Homeostasis breaks down when cells emerge with mutations in tumor suppressor genes or oncogenes. Such mutated cells can have increased net rates of proliferation, which is increased somatic fitness. We show that the best protection against such mutations is achieved when homeostasis is regulated locally via small compartments. Small compartments, on the other hand, allow the accumulation of cells with reduced somatic fitness. Cells with mutations conferring genetic instability normally have a reduced somatic fitness because they have an increased probability of producing deleterious mutations or triggering apoptosis. Thus, small compartments protect against mutations in tumor suppressor genes or oncogenes but promote the emergence of genetic instability.