Unicellular and Multicellular Modes of Selection Impose Distinct Constraints on Cellular Phenotype Evolution

Single-cell sequencing data have shown that cellular phenotypes, like gene expression states, are often low-dimensional, hinting that cellular variation might stem from a smaller set of gene expression programs. A genome essentially provides a collection of cellular phenotypes that can be arranged via various program combinations.

However, the extent of this repertoire exposed to selection differs among organisms. Unicellular organisms usually express different phenotypes across environments or life-cycle stages, so selection within a specific context primarily occurs through the expressed phenotype. In contrast, multicellular organisms can have multiple phenotypes coexisting within an individual and collectively contributing to fitness.

In this study, a geometric model was employed to investigate how selection acting upon cellular phenotypes, either individually or jointly, constrains the capacity of a shared genome to evolve and sustain differentiated phenotypes amidst multiple functional demands. The number of functional demands and the proportion of corresponding phenotypes contributing to fitness were varied.

When demands were weakly divergent, similar evolutionary outcomes were observed. However, with strongly divergent demands, selection on a single phenotype at a time resulted in diminished differentiation as demands accumulated, even when ample programs were at hand. Conversely, as more phenotypes contributed jointly to fitness, differentiation and performance improved.

When all phenotypes contributed jointly, differentiation persisted until demands exceeded the available programs. These findings suggest that the organization of cellular phenotypes over time and space can impose distinct constraints on the evolution of differentiation from a shared genome.