title: Molecular complementarity between simple, universal molecules and ions limited phenotype space in the precursors of cells.
abstract: BACKGROUND
  Fundamental 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.
  
  
  OBJECTIVE
  The 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.
  
  
  METHODS
  We 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.
  
  
  CONCLUSIONS
  We 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.
authors.forename: Vic
authors.initials: V
authors.lastname: Norris
authors.forename: Rosetta N
authors.initials: RN
authors.lastname: Reusch
authors.forename: Kazuei
authors.initials: K
authors.lastname: Igarashi
authors.forename: Robert
authors.initials: R
authors.lastname: Root-Bernstein
mesh_terms: D001419:Bacteria / Q000378:metabolism; D019143:Evolution, Molecular; D006885:Hydroxybutyrates / Q000378:metabolism; D050356:Lipid Metabolism; D008954:Models, Biological; D000069497:Origin of Life; D010641:Phenotype; D011073:Polyamines / Q000378:metabolism; D011122:Polyphosphates / Q000378:metabolism
chemical_list: D006885:Hydroxybutyrates; D011073:Polyamines; D011122:Polyphosphates