The emergence of complex multicellularity represents one of the most profound transitions in the history of life on Earth—a transformation that fundamentally altered biological agency and organization. Despite its importance, we lack a comprehensive understanding of how simple groups of cells evolve into integrated multicellular organisms with specialized reproductive and somatic functions. This knowledge gap stems largely from the fact that this transition occurred hundreds of millions of years ago in lineages whose transitional forms have been lost to extinction.
Using the Multicellularity Long Term Evolution Experiment (MuLTEE) with snowflake yeast, we examine how physical constraints drive the evolution of reproductive specialization during the transition to multicellularity. Our central hypothesis is that cellular entanglement, which evolves as snowflake yeast adapt to form larger and more mechanically robust clusters, creates conditions that naturally partition cells into reproductive and non-reproductive roles—a crucial first step in the evolution of germ-soma differentiation that has been overlooked. We will test this hypothesis by: 1) characterizing the de novo origin of reproductive specialization in the MuLTEE, 2) examining how physically-imposed reproductive specialization alters the course of multicellular evolution, and 3) investigating how biophysical scaffolding bridges the evolution of developmentally-regulated cellular differentiation.
The successful completion of this work will provide unique insight into how biophysical scaffolding can underpin the transition from a multicellular collective to an integrated individual. The insights gained will reshape our understanding of major evolutionary transitions and provide crucial context for understanding diseases like cancer that represent breakdowns in previously-evolved multicellular cooperation and purpose.