Marco Fumasoni: "Experimentally evolving cellular miniaturization"

Cell volume is a fundamental determinant of cellular physiology, maintained through a process known as cell size homeostasis. Studies have shown that large deviations from the typical cell size often produce harmful effects. Nonetheless, cell sizes have dramatically diverged during evolution, ranging from micrometers to millimeters. How does cell size homeostasis evolve to produce such diversity without impacting cell physiology? To address this paradox, we designed an experimental evolution strategy to select progressively smaller cells from Saccharomyces cerevisiae populations. Over 1500 generations, we achieved a five-fold reduction in cell volume compared to wild-type cells, marking the largest decrease observed. We show that the new size homeostasis is stably maintained. Strikingly, evolved cells maintain robust fitness, suggesting that the dramatic change in cell volume did not severely impact physiology. We investigated the genetic basis of cellular miniaturization through whole-genome sequencing of the evolving populations. The roles of known and novel players involved in cell size regulation, as well as putative suppressors of defects associated with cell miniaturization will be discussed. Our results demonstrate the evolutionary plasticity of cell size homeostasis and offer novel insights into how variability in a major cellular feature can be evolutionarily achieved.