Cell death in genome evolution

Abstract

Inappropriate survival of abnormal cells underlies tumorigenesis. Most discoveries about programmed cell death have come from studying model organisms. Revisiting the experimental contexts that inspired these discoveries helps explain confounding biases that inevitably accompany such discoveries. Amending early biases has added a newcomer to the collection of cell death models. Analysis of gene-dependent death in yeast revealed the surprising influence of single gene mutations on subsequent eukaryotic genome evolution. Similar events may influence the selection for mutations during early tumorigenesis. The possibility that an early random mutation might drive the selection for a cancer driver mutation is conceivable but difficult to demonstrate. This was tested in yeast, revealing that mutation of almost any gene appears to specify the selection for a new second mutation. Some human tumors contain pairs of mutant genes homologous to co-occurring mutant genes in yeast. Here we consider how yeast again provide novel insights into tumorigenesis.

Yeast cell death pathway requiring AP-3 vesicle trafficking leads to vacuole/lysosome membrane permeabilization

“…The newly emerging concept is that programmed unicellular death predates and was required for multicellular organisms to arise, rather than the inverse (Huettenbrenner et al, 2003;Iranzo et al, 2014;Vanchurin et al, 2022). While classic apoptosis (caspase-3-mediated cell death) likely arose with metazoans, where it plays a key role in ontogeny, its absence in unicellular organisms does not preclude the concept of self-inflicted unicellular death, because the molecular details of cell death may be as diverse as the organisms themselves (Ameisen, 2002;Teng and Hardwick, 2015).…”

Gene-dependent yeast cell death pathway requires AP-3 vesicle trafficking leading to vacuole membrane permeabilization

“…While there is little doubt that selfish genes drive evolution of cell death (Ramisetty et al, 2015), this does not preclude group level selection theory explanations that accommodate unicellular programmed cell death (Durand, 2020). Similarly, while classic apoptosis (caspase-3-mediated cell death) likely arose with metazoans where it plays a key role in ontogeny, its absence in unicellular organisms does not reject the concept of self-inflicted unicellular death, as the molecular details of cell death may be as diverse as the organisms themselves (Ameisen, 2002;Teng and Hardwick, 2015). However, new parallels between microorganisms and mammals have emerged for non-apoptotic programmed death mechanisms.…”

Filamentation protects Candida albicans from amphotericin B-induced programmed cell death via a mechanism involving the yeast metacaspase, MCA1

“…Specifically, C. albicans cells cultured in media containing the common anti-fungal drugs, amphotericin B (AMB) and caspofungin (CAS), undergo an apoptotic-like programmed cell death 22 23 24 25 . Programmed cell death is a cell suicide program that is essential for homeostasis, development, and disease prevention in many multi-cellular organisms 26 27 28 29 . When it occurs in yeast, programmed cell death is accompanied by the nicking of DNA, the accumulation of reactive oxygen species (ROS), and the intracellular activation of the fungal caspases 30 31 32 33 34 35 36 37 .…”