The Eukaryotic Cell Originated in the Integration and Redistribution of Hyperstructures from Communities of Prokaryotic Cells Based on Molecular Complementarity

In the “ecosystems-first” approach to the origins of life, networks of non-covalent assemblies of molecules (composomes), rather than individual protocells, evolved under the constraints of molecular complementarity. Composomes evolved into the hyperstructures of modern bacteria. We extend the ecosystems-first approach to explain the origin of eukaryotic cells through the integration of mixed populations of bacteria. We suggest that mutualism and symbiosis resulted in cellular mergers entailing the loss of redundant hyperstructures, the uncoupling of transcription and translation, and the emergence of introns and multiple chromosomes. Molecular complementarity also facilitated integration of bacterial hyperstructures to perform cytoskeletal and movement functions

Sensor potency of the moonlighting enzyme-decorated cytoskeleton

Background: There is extensive evidence for the interaction of metabolic enzymes with the eukaryotic cytoskeleton. The significance of these interactions is far from clear. Presentation of the hypothesis: In the cytoskeletal integrative sensor hypothesis presented here, the cytoskeleton senses and integrates the general metabolic activity of the cell. This activity depends on the binding to the cytoskeleton of enzymes and, depending on the nature of the enzyme, this binding may occur if the enzyme is either active or inactive but not both. This enzyme-binding is further proposed to stabilize microtubules and microfilaments and to alter rates of GTP and ATP hydrolysis and their levels. Testing the hypothesis: Evidence consistent with the cytoskeletal integrative sensor hypothesis is presented in the case of glycolysis. Several testable predictions are made. There should be a relationship between post-translational modifications of tubulin and of actin and their interaction with metabolic enzymes. Different conditions of cytoskeletal dynamics and enzyme-cytoskeleton binding should reveal significant differences in local and perhaps global levels and ratios of ATP and GTP. The different functions of moonlighting enzymes should depend on cytoskeletal binding. Implications of the hypothesis: The physical and chemical effects arising from metabolic sensing by the cytoskeleton would have major consequences on cell shape, dynamics and cell cycle progression. The hypothesis provides a framework that helps the significance of the enzyme-decorated cytoskeleton be determined

The correlation between architecture and mRNA abundance in the genetic regulatory network of Escherichia coli

Background: Two aspects of genetic regulatory networks are the static architecture that describes the overall connectivity between the genes and the dynamics that describes the sequence of genes active at any one time as deduced from mRNA abundances. The nature of the relationship between these two aspects of these networks is a fundamental question. To address it, we have used the static architecture of the connectivity of the regulatory proteins of Escherichia coli to analyse their relationship to the abundance of the mRNAs encoding these proteins. In this we build on previous work which uses Boolean network models, but impose biological constraints that cannot be deduced from the mRNA abundances alone. Results: For a cell population of E. coli, we find that there is a strong and statistically significant linear dependence between the abundance of mRNA encoding a regulatory protein and the number of genes regulated by this protein. We use this result, together with the ratio of regulatory repressors to promoters, to simulate numerically a genetic regulatory network of a single cell. The resulting model exhibits similar correlations to that of E. coli. Conclusion: This analysis clarifies the relationship between the static architecture of a regulatory network and the consequences for the dynamics of its pattern of mRNA abundances. It also provides the constraints on the architecture required to construct a model network to simulate mRNA production

Synthetic, Switchable Enzymes

The construction of switchable, radiation-controlled, aptameric enzymes – “swenzymes” – is, in principle, feasible. We propose a strategy to make such catalysts from 2 (or more) aptamers each selected to bind specifically to one of the substrates in, for example, a 2-substrate reaction. Construction of a combinatorial library of candidate swenzymes entails selecting a set of a million aptamers that bind one substrate and a second set of a million aptamers that bind the second substrate; the aptamers in these sets are then linked pairwise by a linker, thus bringing together the substrates. In the presence of the substrates, some linked aptamer pairs catalyze the reaction when exposed to external energy in the form of a specific frequency of low intensity, nonionizing electromagnetic or acoustic radiation. Such swenzymes are detected via a separate product-capturing aptamer that changes conformation on capturing the product; this altered conformation allows it (1) to bind to every potential swenzyme in its vicinity (thereby giving a higher probability of capture to the swenzymes that generate the product) and (2) to bind to a sequence on a magnetic bead (thereby permitting purification of the swenzyme plus product-capturing aptamer by precipitation). Attempts to implement the swenzyme strategy may help elucidate fundamental problems in enzyme catalysis