Quantifying the evolutionary paths to endomembranes.

Eukaryotes exhibit a complex and dynamic internal meshwork of membranes-the endomembrane system-used to insert membrane proteins and ingest food. Verbal models explaining the origin of endomembranes abound, but quantitative considerations of fitness are lacking. Drawing on quantitative data on endomembranes allows for the derivation of two biologically grounded analytical models of endomembrane evolution that quantify organismal fitness: (1) vesicle-based uptake of small nutrient molecules, pinocytosis, and (2) vesicle-based insertion of membrane proteins, proto-endoplasmic reticulum. Surprisingly, pinocytosis of small-molecule nutrients does not provide a net fitness gain under biologically sensible parameter ranges, explaining why pinocytosis is primarily used for protein uptake in contemporary organisms. The proto-endoplasmic reticulum does provide net fitness gains, making it the more likely candidate for initiating the endomembrane system. With modifications, the approach developed here can be used more generally to understand the present-day endomembrane system and illuminate the origin of the eukaryotic cell.