Oxygen suppression of macroscopic multicellularity

Atmospheric oxygen is thought to have played a vital role in the evolution of large, complex multicellular organisms. Challenging the prevailing theory, we show that the transition from an anaerobic to an aerobic world can strongly suppress the evolution of macroscopic multicellularity. Here we select for increased size in multicellular ‘snowflake’ yeast across a range of metabolically-available O2 levels. While yeast under anaerobic and high-O2 conditions evolved to be considerably larger, intermediate O2 constrained the evolution of large size. Through sequencing and synthetic strain construction, we confirm that this is due to O2-mediated divergent selection acting on organism size. We show via mathematical modeling that our results stem from nearly universal evolutionary and biophysical trade-offs, and thus should apply broadly. These results highlight the fact that oxygen is a double-edged sword: while it provides significant metabolic advantages, selection for efficient use of this resource may paradoxically suppress the evolution of macroscopic multicellular organisms.