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.

Geometry, packing, and evolutionary paths to increased multicellular size

“…This facilitates multicellular adaptation, as it limits the potential for within-organism genetic conflict and promotes the emergence of novel, heritable multicellular traits [26]. Snowflake yeast readily adapt as multicellular individuals, evolving to be more complex by gaining novel multicellular traits [13,17,27]. Indeed, complex multicelluarity (i.e., metazoans, land plants, red algae, brown algae and fungi) has only evolved in organisms that develop clonally [28].…”

Aspects of Multicellularity in Saccharomyces cerevisiae Yeast: A Review of Evolutionary and Physiological Mechanisms

“…Apoptosis was shown to be a trait co-evolving with increased cluster size, not a direct effect of its size. As such, apoptosis is interpreted as an adaptive altruistic trait underpinning cellular division of labour [ 74 ].…”

Evolution of altruistic cooperation among nascent multicellular organisms

“…We measured the size distribution of clusters by following the protocol of Pentz et al (2016). Briefly, we fluorescently labeled vacuoles with CTB, then, after a 30-min incubation in the dark, imaged flattened clusters using wide field microscopy (35 stitched fields of view taken with a 10× objective on a Nikon Ti-E inverted microscope).…”

“…This ensures that mutations are rapidly segregated between cellular groups (Ratcliff et al 2015a), allowing selection to act on emergent multicellular traits that arise as a consequence of novel mutations (Ratcliff et al 2017). Multicellular selection readily acts on these traits, increasing the frequency of multicellular adaptations such as elongate cells, which result in the formation of larger groups by increasing cellular packing density (Jacobeen et al 2018), and elevated programmed cell death (PCD), which results in the production of smaller, faster-growing propagules that repeatedly displace clusters with lower rates of PCD (Ratcliff et al 2012;Pentz et al 2016).…”