An adaptationist view of apoptosis.

Abstract

A cell's decision whether to undergo apoptosis (cell suicide) is examined here from an adaptationist perspective, rather than a mechanistic one. External and internal inputs to the cell's protein-based information processing network are used in making this decision, with the cell factoring in its replaceability. A system in which each cell takes primary responsibility for deciding its own fate has great adaptive value because it harnesses each cell's self-knowledge rather than waiting for external cues to be recognized by other cells. Cell self-destruction can be an important selective mechanism, potentially leading to better performance of tissues over time. However, reliance on cells to monitor themselves has a flaw, since cells may incur selfish mutations that impair their apoptotic responsibility. The tight control exerted over somatic cells serves to check selfish genes involved in neoplasia and viral infections. Germ cells appear to be similarly monitored, both by other germ cells and by supporting follicular or Sertoli cells, thus maintaining the advantages offered by an apoptotic system. The adaptationist approach views the limited replacement of neurons and cardiac myocytes as likely to have net survival value. The linkage of these cells into a network with their neighbors throughout a lifetime allows for a precisely functioning team of cells expected to compensate for gradual declines in individual cell functionality. Replacement of apoptotic cells with naive cells might decrease brain functionality and might risk upsetting the conduction of cardiac impulses. The evolutionary viewpoint lends itself to new hypotheses, but only the boldest speculator would have predicted a system in which cells are given primary responsibility for deciding whether to kill themselves when they deem it beneficial to the organism.