The Origin and Evolution of Programmed Cell Death


Programmed cell death and apoptosis have been assumed to emerge with multicellularity, and to depend on specific ‘death genes’ whose sole effects are execution or repression of cell death. In 1996, I proposed the ‘original sin’ hypothesis, postulating that the origin of self‐destruction is as ancient as the origin of the first cells, and predicting that there are no specific ‘death genes’. Rather, an ancestral and unavoidable capacity of effectors of cell survival – of cell metabolism, differentiation, cycling – to induce cell death favoured their continuous selection during evolution for both their ‘pro‐life’ and ‘pro‐death’ activities. Diversification of these effectors was accelerated by their recruitment into host/parasite interactions and symbioses, including the one that gave birth to eukaryote cells. The main prediction of the ‘original sin’ hypothesis is supported by recent findings showing that effectors of cell death indeed have previously undetected roles in cell survival.

Key concepts

  • Programmed cell death (PCD) is an evolutionary conserved, regulated process of cell suicide crucial in the development and homeostasis of multicellular animals and plants.

  • Various forms of PCD have also been discovered in unicellular organisms, including bacteria, favouring the survival in adverse environments of a part of the colony at the expense of the premature dismissal of another.

  • Because PCD appears as an ‘altruistic’ cell response, the evolutionary origin of PCD has been equated with that of ‘altruistic’ cell behaviour.

  • The ‘original sin’ hypothesis postulates that the origin of PCD is as ancient as the origin of the first cell, resulting from an unavoidable capacity of most molecular effectors of cell survival (metabolism, differentiation and cell cycle) to induce stochastic self‐destruction, when their activity is not regulated by other cell survival effectors acting as partial antagonists.

  • The ‘original sin’ hypothesis predicts that there are no specific ‘death genes’; rather, the ancestral capacity of most effectors of cell survival to also induce cell suicide allowed their continuous selection during evolution for both their ‘pro‐life’ and ‘pro‐death’ activities.

  • Some of the pleiotropic ‘pro‐life’ and ‘pro‐death’ effectors diversified and propagated in bacteria as toxin/antidote ‘addiction modules’, achieving a form of enforced symbiosis, because their dismissal results in the self‐destruction of the cell in which they reside.

  • Host/parasite conflicts, lateral gene transfers and enforced symbioses – between bacteria and their ‘addiction modules’ of plasmid origin, and later between eukaryote cells and their mitochondria endosymbionts of bacterial origin – played a crucial role in the subsequent diversification and propagation of PCD.

  • The seminal studies of the genetic control of PCD in the nematode Caenorhabditis elegans implied that executioners and repressors of PCD had no other possible effect than execution or repression of cell death; however, a series of recent findings indicates that executioners and repressors of PCD exert other previously undetected vital effects in both multicellular and unicellular organisms.

Keywords: evolution; programmed cell death; apoptosis; unicellular organisms; bacteria; ageing


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Ameisen, Jean Claude(Dec 2009) The Origin and Evolution of Programmed Cell Death. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0021988]