To understand the emergence of Darwinian evolution, it is necessary to identify physical mechanisms that enabled primitive cells to compete with one another. Whereas all modern cell membranes are composed primarily of diacyl or dialkyl glycerol phospholipids, the first cell membranes are thought to have self-assembled from simple, single-chain lipids synthesized in the environment. We asked what selective advantage could have driven the transition from primitive to modern membranes, especially during early stages characterized by low levels of membrane phospholipid. Here we demonstrate that surprisingly low levels of phospholipids can drive protocell membrane growth during competition for single-chain lipids. Growth results from the decreasing fatty acid efflux from membranes with increasing phospholipid content. The ability to synthesize phospholipids from single-chain substrates would have therefore been highly advantageous for early cells competing for a limited supply of lipids. We show that the resulting increase in membrane phospholipid content would have led to a cascade of new selective pressures for the evolution of metabolic and transport machinery to overcome the reduced membrane permeability of diacyl lipid membranes. The evolution of phospholipid membranes could thus have been a deterministic outcome of intrinsic physical processes and a key driving force for early cellular evolution.origin of life | ribozymes | coevolution T he first cell membranes are likely to have formed from simple, single-chain lipids such as short-chain fatty acids and their derivatives that were present in the prebiotic environment (1, 2). Membranes composed of such amphiphiles are permeable to polar nutrients such as nucleotides (3) and feature the dynamic properties necessary for spontaneous growth and division (2, 4). The high permeability of fatty-acid-based membranes is consistent with a heterotrophic model for early cells, in which chemical building blocks are synthesized in the environment and passively diffuse across the cell membrane to participate in replication. All modern cells synthesize phospholipids (or sulfolipids in rare exceptions; refs. 5 and 6) with two hydrophobic chains as their primary membrane lipids. Phospholipid membranes prevent the rapid permeation of ions and polar molecules, allowing modern cells to retain internally synthesized metabolites and to control all import and export. The evolution of phospholipid membranes must have therefore mirrored the emergence of metabolic and transport machinery during early cellular evolution.This transition from single-chain lipids to phospholipids had to be gradual, both to allow for the coevolution of metabolic and transport machinery and because of the initial inefficiency of nascent catalysts (e.g., ribozymes). Hence, the selective advantage associated with phospholipid synthesis had to apply to small differences in phospholipid content in order to drive this transition. What selective advantage could be conferred by the low levels of phospholipid that mus...

Lipid composition determines the physical properties of biological membranes and can vary substantially between and within organisms. We describe a specific role for the viscosity of energy-transducing membranes in cellular respiration. Engineering of fatty acid biosynthesis in Escherichia coli allowed us to titrate inner membrane viscosity across a 10-fold range by controlling the abundance of unsaturated or branched lipids. These fluidizing lipids tightly controlled respiratory metabolism, an effect that can be explained with a quantitative model of the electron transport chain (ETC) that features diffusion-coupled reactions between enzymes and electron carriers (quinones). Lipid unsaturation also modulated mitochondrial respiration in engineered budding yeast strains. Thus, diffusion in the ETC may serve as an evolutionary constraint for lipid composition in respiratory membranes.

Recent synthetic approaches to understanding the origin of life have yielded insights into plausible pathways for the emergence of the first cells. Here we review current experiments with implications for the origin of life, emphasizing the ability of unexpected physical processes to facilitate the self-assembly and self-replication of the first biological systems. These laboratory efforts have uncovered novel physical mechanisms for the emergence of homochirality; the concentration and purification of prebiotic building blocks; and the ability of the first cells to assemble, grow, divide, and acquire greater complexity. In the absence of evolved biochemical capabilities, such physical processes likely played an essential role in early biology.