Quiescence Through the Prism of Evolution

Abstract

Being able to reproduce and survive is fundamental to all forms of life. In primitive unicellular organisms, the emergence of quiescence as a reversible proliferation arrest has most likely improved cell survival under unfavorable environmental conditions. During evolution, with the repeated appearances of multicellularity, several aspects of unicellular quiescence were conserved while new quiescent cell intrinsic abilities arose. We propose that the formation of a microenvironment by neighboring cells has allowed disconnecting quiescence from nutritional cues. In this new context, non-proliferative cells can stay metabolically active, potentially authorizing the emergence of new quiescent cell properties, and thereby favoring cell specialization. Through its co-evolution with cell specialization, quiescence may have been a key motor of the fascinating diversity of multicellular complexity.

Keywords: evolution; microenvironment; multicellularity; quiescence; unicellular organism.

FIGURE 1

(A) Emergence of microenvironment and cell specialization. By “simple multicellular organism,” we mean a multicellular entity composed of identical cells and by “complex multicellular organism,” an organism composed of non-identical cells i.e., cells with different cellular properties. As such, “complex multicellularity” emerged together with cell specialization. Multicellularity physically generates a microenvironment that isolates some cells from the direct contact with macroenvironment. Complex microenvironment (secreted metabolites, diffusive proteins, extracellular matrix, etc.) and the tissue architecture become key in controlling quiescence. Hence, multicellularity may have allowed quiescence to evolve away from nutritional signals. (B) Quiescence in a buffered microenvironment favors the emergence of cell specialization, which in turn generates a more complex microenvironment hence closing an auto-complexification loop.