Genome duplication and mutations in <i>ACE2</i> cause multicellular, fast-sedimenting phenotypes in evolved <i>Saccharomyces cerevisiae</i>

Significance The shift from unicellular to multicellular life forms represents a key innovation step in the evolution of life on Earth. However, knowledge on the evolutionary pressures resulting in the selection of multicellular life forms and the underlying molecular mechanisms is far from complete. Our study provides a complete identification of the specific genetic changes by which the unicellular eukaryote S. cerevisiae can acquire a multicellular, fast-sedimenting phenotype. We demonstrated that a minimal evolutionary mechanism encompassed a deregulation of the late step of the cell cycle through mutation in ACE2 followed by whole genome duplication.