A compositional view comparing modern biological condensates and primitive phase‐separated compartments

Abstract

Liquid–liquid phase separation (LLPS) is a process that often occurs due to binding between oppositely charged biopolymers, and has gained increasing attention recently due to their ubiquity in biological systems and ability to direct essential cellular processes. However, while these discoveries in biology are recent, the field of origins of life has been investigating LLPS for nearly 100 years, ever since the first suggestions by Oparin and Haldane that primitive LLPS could have been precursors to the first cells on Earth. Since then, a significant amount of work has been done to elucidate different primitive LLPS systems that could have been relevant as protocellular models. Given the structural similarities between primitive LLPS and modern membraneless organelles, there may even be an evolutionary link between the two, although this remains a question to be answered. Nevertheless, in order to answer this, a source that compares compositional aspects of modern biological condensates and primitive LLPS is necessary. Here, we first focus on membraneless organelles composed of intrinsically disordered proteins (IDPs) and nucleic acids. Then, as a parallel, we explore primitive membraneless compartments composed of simple biopolymers such as short peptides and nucleic acids. This is followed by a discussion of how the first biomolecules on Earth may have originated, analyzing the environmental and chemical conditions that could have favored primitive LLPS processes. Finally, we directly compare composition of modern biological condensates and primitive phase‐separated compartments, further discussing the potential of primitive IDPs on early Earth, but also the evolution from membraneless to membrane‐bound cells. This review aims to provide a compositional comparison of modern and primitive phase‐separated structures in order to help researchers in both fields understand the current state of knowledge, how this knowledge evolved, and the current gaps that need to be further addressed.

The interplay between peptides and RNA is critical for protoribosome compartmentalization and stability

“…Because of the high RNA-peptide LLPS propensity, coacervates have been proposed as a unique environment supporting co-evolution of those species (16). Current studies are now researching the impact of different environments as well as the polymer properties and lengths on the coacervation propensities (43) (44). The bigger construct used in our study, bPTC, is structurally more rigid and interacts with the rPeptides with higher specificity.…”

Proto-Neurons from Abiotic Polypeptides

“…Upon hydration, Fox's proteinoids exhibit a remarkable ability to self-assemble into spherical vesicles. These microspherical membranes serve as a model for the formation of semi-permeable protocell structures from simple abiotic polypeptides [64][65][66][67][68][69].…”