American Society of Naturalists

"Disentangling the Factors Selecting for Unicellular Programmed Cell Death"

J. David Van Dyken and Peter C. Zee: Read the article

Sometimes, survival depends on knowing when to die, much like programmed cell death. Programmed cell death is a perhaps counterintuitive adaptation critical to one of the most important evolutionary developments of life on earth, the emergence of multicellular life from their single-celled ancestors. The ability of cells to undergo programmed cell death (PCD) is fundamental to the emergence and evolutionary stability of multicellular life. From embryonic development to preventing diseases such as cancer, PCD was an evolutionary innovation of spectacular importance. Despite its ubiquity in metazoan life, the evolutionary origin of PCD and a complete understanding of its impact on the fitness of individual organisms remains unresolved. Many researchers have pointed out that programmed cell death likely originates in unicellular life, from which multicellular species have evolved several times independently.

In their recent publication, Dr. Van Dyken and Dr. Zee developed mathematical models to explore how PCD may have been selectively advantageous to unicellular cells in various ecological conditions. The standing hypothesis in the evolution of PCD is that the selective advantage of PCD to unicellular cells can be understood best through Hamilton’s rule. Put simply, the late W.D. Hamilton posited that an individual’s probability of acting altruistically (here, a cell triggering its death) is proportional to its relatedness to the affected individuals and the benefit the altruistic behavior provides to those individuals.

The problem with this understanding of the evolution of programmed cell death, the authors of this study point out, is that if individual cells carry the gene that allows for altruistic programmed cell death, how does it expand in a population if the carrier is always set to self-destruction? Several studies have suggested that some mechanism to interrupt the programmed cell death stochastically must exist for it to have propagated in unicellular populations. The results of Dr. Van Dyken and Dr. Zee’s mathematical model highlight that some ability for a unicellular cell to “sense” either its reproductive potential or external stressors (e.g., resource availability) must exist for the selective advantage of PCD to persist. Ultimately, the work of Dr. Van Dyken and Dr. Zee illuminates that in the evolution of multicellularity, the secret to survival may lie in knowing when to sacrifice.

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Dr. Zachary Compton received his doctorate in Evolutionary Biology at Arizona State University. He is currently an NIH T32 Postdoctoral Fellow at the University of Arizona Cancer Center and the College of Medicine. He is interested in all the intersections that cancer biology makes with evolutionary theory, particularly comparative oncology - the study of cancer across the tree of life. Dr. Compton is the co-founder and former director of the Arizona Cancer Evolution (ACE) Scholars program, one of the country's largest undergraduate research training programs, where he now serves as a scientific advisor. He is passionate about bringing evolution into the cancer clinic and the community.