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

Abstract

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

Secretory Conservation in Insulin Producing Cells: Is There a System-Level Law of Mass Action in Biology?

“…Due to our interest in secreted proteins, we first identified that 630 of these genes were extracellular (see the Materials and Methods section). Of these 630 extracellular genes, 310 correspond to nonmembrane (i.e., may be assumed to be soluble proteins that were secreted) and 320 correspond to membrane proteins (i.e., may be assumed to be extracellular membrane proteins including those associated with secreted vesicles) …”

“…The science of biology, however, is yet to benefit from the general acceptance of even a single universally applicable tenet despite some recent discoveries. − Arguably, the only consensus definition in biological sciences is that of a cell as a unit of life. Even the unparalleled discovery of the central dogma, earlier believed to be universal, does not apply to certain aspects of biological replication . On the one hand, a case-by-case assessment of phenomena renders biological sciences relatively empirical.…”

“…Even the unparalleled discovery of the central dogma, 39 earlier believed to be universal, does not apply to certain aspects of biological replication. 18 On the one hand, a case-by-case assessment of phenomena renders biological sciences relatively empirical. On the other hand, continuing challenges associated with the discovery of exception-free universal features/signatures in systems are a major source of excitement in biological research.…”

“…Of these 630 extracellular genes, 310 correspond to nonmembrane (i.e., may be assumed to be soluble proteins that were secreted) and 320 correspond to membrane proteins (i.e., may be assumed to be extracellular membrane proteins including those associated with secreted vesicles). 18 In transcriptome studies, we have further filtered out a total of 630 extracellular proteins (nonmembrane 310 and membrane 320) from successfully expressed protein-coding genes, which have been shown in the outline flow in Figure 2a. The vein diagram in Figure 2b demonstrates the distribution of extracellular secreted proteins.…”

Pseudopeptosomes: non-lipidated vesicular assemblies from bispidine-appended pseudopeptides

“…In general, it is thought that vesicular assemblies, mimicking biological cells and subcellular compartments, are formed due to the hydrophobically-driven self-assembly of amphiphilic molecules in aqueous environments. 22,[37][38][39][40] At the same time, manifestations of biological functions result from the action of polymeric structures ( predominantly proteins) within particular ranges of environmental variables. 41,42 Vesicular assemblies utilize the full spectrum of four weak interactions (hydrogen-bonding, ionic interactions, van der Waals forces and hydrophobic interactions).…”