Apoptosis in snowflake yeast: novel trait, or side effect of toxic waste?

Abstract

Recent experiments evolving de novo multicellularity in yeast have found that large cluster-forming genotypes also exhibit higher rates of programmed cell death (apoptosis). This was previously interpreted as the evolution of a simple form of cellular division of labour: apoptosis results in the scission of cell-cell connections, allowing snowflake yeast to produce proportionally smaller, faster-growing propagules. Through spatial simulations, Duran-Nebreda and Solé (J. R. Soc. Interface 12, 20140982 (doi:10.1073/pnas.1115323109)) develop the novel null hypothesis that apoptosis is not an adaptation, per se, but is instead caused by the accumulation of toxic metabolites in large clusters. Here we test this hypothesis by synthetically creating unicellular derivatives of snowflake yeast through functional complementation with the ancestral ACE2 allele. We find that multicellular snowflake yeast with elevated apoptosis exhibit a similar rate of apoptosis when cultured as single cells. We also show that larger snowflake yeast clusters tend to contain a greater fraction of older, senescent cells, which may explain why larger clusters of a given genotype are more apoptotic. Our results show that apoptosis is not caused by side effects of spatial structure, such as starvation or waste product accumulation, and are consistent with the hypothesis that elevated apoptosis is a trait that co-evolves with large cluster size.