Molecular complementarity between simple, universal molecules and ions limited phenotype space in the precursors of cells

Abstract

BackgroundFundamental problems faced by the protocells and their modern descendants include how to go from one phenotypic state to another; escape from a basin of attraction in the space of phenotypes; reconcile conflicting growth and survival strategies (and thereby live on ‘the scales of equilibria’); and create a coherent, reproducible phenotype from a multitude of constituents.Presentation of the hypothesisThe solutions to these problems are likely to be found with the organic and inorganic molecules and inorganic ions that constituted protocells, which we term SUMIs for Simple Universal Molecules and Ions. These SUMIs probably included polyphosphate (PolyP) as a source of energy and of phosphate; poly-(R)-3-hydroxybutyrate (PHB) as a source of carbon and as a transporter in association with PolyP; polyamines as a source of nitrogen; lipids as precursors of membranes; as well as peptides, nucleic acids, and calcium. Here, we explore the hypothesis that the direct interactions between PHB, PolyP, polyamines and lipids – modulated by calcium – played a central role in solving the fundamental problems faced by early and modern cells.Testing the hypothesisWe review evidence that SUMIs (1) were abundant and available to protocells; (2) are widespread in modern cells; (3) interact with one another and other cellular constituents to create structures with new functions surprisingly similar to those of proteins and RNA; (4) are essential to creating coherent phenotypes in modern bacteria. SUMIs are therefore natural candidates for reducing the immensity of phenotype space and making the transition from a “primordial soup” to living cells.Implications of the hypothesisWe discuss the relevance of the SUMIs and their interactions to the ideas of molecular complementarity, composomes (molecular aggregates with hereditary properties based on molecular complementarity), and a prebiotic ecology of co-evolving populations of composomes. In particular, we propose that SUMIs might limit the initial phenotype space of composomes in a coherent way. As examples, we propose that acidocalcisomes arose from interactions and self-selection among SUMIs and that the phosphorylation of proteins in modern cells had its origin in the covalent modification of proteins by PHB.ReviewersThis article was reviewed by Doron Lancet and Kepa Ruiz-Mirazo.

Protein Quality Control under Oxidative Stress Conditions

“…Polyphosphates (polyP) are prebiotic polymers (132): highly conserved, universal and structurally extremely simple. They exist as long, typically unbranched chains of phosphoanhydride bond-linked phosphates, which can reach lengths of up to 1000 P i units (133).…”

Why do bacteria divide?

“…One approach is to focus on those unifying problems that recur in different fields, for example, how to limit the enormity of phenotype space so that Darwinian selection can act ( Kauffman, 1996 ). To solve this problem, we have invoked a key role for simple, universal molecules and inorganic ions, termed SUMIs, which include polyphosphate, polyhydroxybutyrate, polyamines, and calcium ( Norris et al, 2015 ). A complementary approach is to ask whether the paradigm would help elucidate another field, for example, could a hypothesis developed for the origins of life help with cell division?…”

“…In the latter case, accumulation of cardiolipin would be an attractive candidate given its roles in initiation of replication ( Sekimizu and Kornberg, 1988 ; Makise et al, 2002 ) and in cell division ( Mileykovskaya and Dowhan, 2000 ; Koppelman et al, 2001 ; Kawai et al, 2004 ). Finally, there are molecules of major physiological importance that are often overlooked ( Norris et al, 2015 ); these include polyphosphate which, in some bacteria, has been shown to play a role in the cell cycle ( Boutte et al, 2012 ) and to exist in both soluble and insoluble forms ( Klauth et al, 2006 ).…”

Inorganic polyphosphate is produced and hydrolyzed in F0F1-ATP synthase of mammalian mitochondria

“…An importance of polyP for the proper function of the mitochondrial NAD kinase [21,22] has been shown, which potentially affects the total mitochondrial metabolism. The role of polyP as an energy source for the ATPase has been already discussed [23]. However, there are still a large number of open questions concerning the role of polyP in energy metabolism [23]: (a) it is still not clear whether polyP could act as an energy molecule in mammalian cells, being utilized in the various types of ATPases; (b) how is polyP produced or elongated in mitochondria and how this polymer affects mitochondrial respiration and ultimately oxidative phosphorylation.…”