Aspects of Biological Replication and Evolution Independent of the Central Dogma: Insights from Protein-Free Vesicular Transformations and Protein-Mediated Membrane Remodeling

Biological membrane remodeling is central to living systems. In spite of serving as “containers” of whole-living systems and functioning as dynamic compartments within living systems, biological membranes still find a “blue collar” treatment compared to the “white collar” nucleic acids and proteins in biology. This may be attributable to the fact that scientific literature on biological membrane remodeling is only 50 years old compared to ~ 150 years of literature on proteins and a little less than 100 years on nucleic acids. However, recently, evidence for symbiotic origins of eukaryotic cells from data only on biological membranes was reported. This, coupled with appreciation of reproducible amphiphilic self-assemblies in aqueous environments (mimicking replication), has already initiated discussions on origins of life beyond nucleic acids and proteins. This work presents a comprehensive compilation and meta-analyses of data on self-assembly and vesicular transformations in biological membranes—starting from model membranes to establishment of Influenza Hemagglutinin-mediated membrane fusion as a prototypical remodeling system to a thorough comparison between enveloped mammalian viruses and cellular vesicles. We show that viral membrane fusion proteins, in addition to obeying “stoichiometry-driven protein folding”, have tighter compositional constraints on their amino acid occurrences than general-structured proteins, regardless of type/class. From the perspective of vesicular assemblies and biological membrane remodeling (with and without proteins) we find that cellular vesicles are quite different from viruses. Finally, we propose that in addition to pre-existing thermodynamic frameworks, kinetic considerations in de novo formation of metastable membrane structures with available “third-party” constituents (including proteins) were not only crucial for origins of life but also continue to offer morphological replication and/or functional mechanisms in modern life forms, independent of the central dogma. GRAPHIC ABSTRACT: [Image: see text]