aa r X i v : . [ q - b i o . O T ] M a y A Prerequisite for Life
Søren Toxvaerd
Department of Science and Environment, Roskilde University, Postbox 260, DK-4000Roskilde, Denmark
Abstract
The complex physicochemical structures and chemical reactions in living or-ganism have some common features: (1) The life processes take place in thecytosol in the cells, which, from a physicochemical point of view is an emul-sion of biomolecules in a dilute aqueous suspension. (2) All living systems arehomochiral with respect to the units of amino acids and carbohydrates, but(some) proteins are chiral unstable in the cytosol. (3) And living organismare mortal. These three common features together give a prerequisite for theprebiotic self-assembly at the start of the Abiogenesis. Here we argue , thatit all together indicates, that the prebiotic self-assembly of structures andreactions took place in a more saline environment, whereby the homochi-rality of proteins not only could be obtained, but also preserved. A moresaline environment for the prebiotic self-assembly of organic molecules andestablishment of biochemical reactions could have been the hydrothermalvents.
Keywords:
Abiogenesis, Homochirality, Prebiotic environment
1. Introduction
Numerous articles deal with the environmental and physicochemical con-ditions for -, and with the chemical reactions at the establishment of life onplanet Earth, or somewhere else in the universe [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11].Many of the suggestions are inspired by Darwin, and link these conditionsand reactions with the chemical composition and reactions in LUCA, our lastuniversal common ancestor [12, 13]. It is, however, not clear whether LUCAis a simple Archaea or Bacteria, or whether it is a more primitive organism,a Progenote [14, 15, 16, 17, 18]. For a recent review see [19]. But althoughLUCA, superficially looks rather simple, it is in fact very complicated and
Preprint submitted to Journal of Theoretical Biology May 23, 2019 ighly structured [17, 19], and with all the fundamental preconditions for ourlife. LUCA has a genetics and a metabolism controlled by enzymes in a cellwith ion channels and active transport.Our first ancestor is at least 3.5 billion years (Ga) old [20, 21], and thereis indirect signs of life even before 3.5 Ga [22, 23]. The earth is ≈ Hydra vulgaris ,show no sign of mortality for a period of four years [26], and some jellyfishperform life cycle reversal [27]. Another example is the stability of the enzymetelomerase and the telomere. Together they are responsible for the unlimitedproliferation of almost all cancer cells [28].With respect to the necessity of homochirality of the units of amino acidsand carbohydrates, it is in general not debated in articles, which deal with theprerequisites for life. But here we argue, that the three common properties:the composition of the cytosol, the instability of homochirality in enzymesand mortal instability of living systems, are connected, and that they togetheralso is a key to determine a prerequisite for our life: prebiotic self-assemblyof homochiral enzymes in a saline aqueous environment.2 . The aqueous cytosol solution in the cells, homochirality and life
All the cells in living organisms are soft condensed matter, limited by cellmembranes and the cells contain an aqueous (cytosol) suspension of organicmolecules. The cytosol can be characterized as a diluted aqueous solutionof cat- and anions at a total concentration (exclusive amino acids) of ≈ + ] ≈ + ] ≈ − ] ≈ − , Ca ++ , Mg ++ ,.., with smaller concentrations. Despite the small ionicconcentrations in the cell interior, the cytostol with a complex cytoplasmwith water networks and hyperstructures [29, 30], departs physicochemicalfrom the condition of an ideal aqueous solution [31].LUCA is at least 3.5 billion years (Ga) old, and it is therefore naturalto describe how the earth was, and how water appeared, at that time. Theearth is ≈ + ] ≈ + ] ≈ − M. The differencebetween the concentrations of sodium and potassium outside and inside thecell is vital and maintained by the sodium pump.Living systems consist of peptides with units of L-amino acids and D-carbohydrates. The amino acids have, however, an active isomerization ki-netics and will racemize in an aqueous solution [35]. The chirality of a peptidein a cell is also unstable [36]. But from computer simulations and thermo-dynamic investigations of aqueous suspensions of peptide-like molecules atdifferent water activities one finds, that although peptides lose their homochi-rality at high water activity, they are stable and maintain homochirality ata lower water activity (saline solutions) [37], in accordance with the obser-vation of the stability of homochirality in a peptide. The physicochemicalexplanation for this behaviour is, that the compact α -helix structure, pre-dicted by Pauling et al. [38, 39], ensures a sufficient chiral discriminationfor obtaining and maintaining homochirality, but provided that the wateractivity is sufficiently low [40]. According to Pauling, the α -helix struc-ture is ensured by weak hydrogen-like bonds between units in the helix. But these bonds are in competition with hydrogen bonds to the attached wa- er molecules at the protein, which destabilizes the α -helix structure at highwater activity (i.e. concentration). It is, however, only the stability of homochirality in the proteins, whichdepends on the salinity of the aqueous cytosol suspension, because the ho-mochirality of carbohydrates is obtained and ensured in a different way, bystereo specific enzymes in the metabolism [40]. All polymer units in carbo-hydrates have a D-configuration at carbon atom No. 5 for hexose-units andNo, 4 for pentose-units. The carbohydrate polymers in biosystems are syn-thezised from Glyceraldehyde-3-phosphate, which has a very active isomer-ization kinetics. The isomerization kinetics for Glyceraldehyde-3-phosphateis catalysed by the extreme effective enzyme, Triose Phosphate Isomerase,and it looks like a paradox, that the bio-carbohydrate wold is 100% ho-mochiral, when the key-molecule in the polymerization is chiral unstable.But the explanation of this paradox is, that once the polymerization withGlyceraldehyde-3-phosphate starts by creation of a hexose or a pentose (Ri-bose), the chiral center in Glyseraldehyde-3-phosphate is preserved by stablecovalent bonds [41], and the total dominance of the D-configurations in bio-carbohydrates is obtained and maintained by stereo specific enzymes [40].That proteins and enzymes are homochiral stable at a low water activ-ity, is a daily life’s observation. One can conserve meat in a salty- or sugarsolutions, whereby the bacteria are dehydrated and inactive. But their lifeis only set on “stand-by” in the salty solution, and some bacteria can evensurvive in a dehydrated state under extreme conditions of pressure and tem-perature for a very long time [42]. It is therefore natural to conclude, thatthe prebiotic self-assembly of peptides from units of amino acids took placein an environment with higher salinity and lower water activity than in thecytosol, whereby one not only could obtain, but also maintain homochiralityby the peptide synthesis [37].
3. Darwin’s warm little pond
There has been many proposals to the geographic location(s), where lifeoccurred. The Hadean ocean(s), tidal pools, icy environments, mineral sur-faces, alkaline hydrothermal vents, to mention some proposals, which also in-cludes extraterrestrial places. This article focus on the necessity of a rathersalty solution with a relative high concentration of the building blocks ofamino acids in order to ensure a sufficient strength of chiral discriminationat the peptide polymerization. It has always been a puzzle, from where the4mino acids came, but in fact this question is irrelevant for the start of theAbiogenesis. The problem is not from where they came, or whether or notthe amino acids were in a racemic or homochiral composition. The aminoacids have an active isomerization kinetics, and an aqueous solution of aminoacids will racemize over time [35]. The problem is how to maintain a suffi-cient high concentration of amino acids for the polymerization, and to howensure a homochiral stable form for a very long time. So long to that theother self-assembly of higher order structures and consecutive reactions in biosystems could be established. The necessity of a high concentration of aminoacids exclude the bulk ocean(s) and points to places with “confine geome-try”. Because, if the prebiodic polymerization of peptides had occurred in awell stirred Hadean ocean, it would require an enormous amount of aminoacids.In a letter to a close friend Darwin proposed, that life were started “ ..insome warm little pond..” [43], and since then there has been many sugges-tions to where in the aqueous environment the life processes started. TheDarwinism is often presented as a continuous coherent evolution from simpleinorganic processes toward the living systems. This outlook of the emergenceof living systems as prebiotic “ chemistry in a bag” has been criticised [11].Branscomb and Russell noticed, that all living systems exist in a self-generatephysical state, that is extremely far from thermodynamic equilibrium i.e.,equivalently, of extremely low entropy and thus of correspondingly low prob-ability. They conclude, that a simple mass-action chemistry cannot explainthe self-generated and far-from -equilibrium myriad of disequilibrium in aliving organism.The living organism is in a “ far from equilibrium” state with gradients inthe electrical potential, and protonic and ionic concentrations. These factsexcludes most of the proposed locations for the prebiotic self-assembly ofthe building blocks. The most favorable place, however, is the submarinealkaline hydrothermal vents, where the confined environment with protonic,ionic and concentration gradients fulfil the requirements for non-equilibriumself-assembly of higher order organic structures [7, 11, 44, 45]. In this contextit is interesting to notice, that the earliest sign of life is located to be in fluvialhot spring deposits [20].It is natural to connect the evolution of bio systems with the geologicalevolution. The geology of the planet Earth has changed significantly overtime, and the physicochemical environment, where the prebiotic self-assemblytook place, must also have changed during the prebiotic time. This fact might5xplain how the strong non-equilibrium chemistry with differences in ionconcentrations between the cytosol and the aqueous environment have beenestablished. Could it not have happened, that e.g. emulsion of peptides weresynthesised as “chemistry in a bag” in the vents or in the confine geometrybelow the vents, and then were exposed to drastic changes in concentrationscaused be changes in the vents? LUCA is a space shuttle, not a shuttlein an empty space, but “ chemistry in a bag” in a hostile salty sea. Weare used to consider the sodium pump as a physicochemical mechanism toensure a potential difference at the membrane and a gradient in sodium andpotassium. But the ion channels also ensure a low salinity in the cells, whichis a necessity for our life processes.
4. Discussion
The Abiogenesis, or the origin of life, is probably not a result of a series ofsingle events, but rather the result of a gradual process with increasing com-plexity of molecules and chemical reactions, and the prebiotic synthesis mightnot have left any trace of the establishment of structures and reactions at thebeginning of the evolution [4, 46, 47]. But the evolution have lead to differentforms of the most simple living systems. There exists two forms of simpleprocariotes: bacteria and the archaea, who mainly differ with respect to theconstitutions of their membranes. Their metabolism, genetics and enzymesystems are qualitative the same, and they are both homochiral with respectto their peptide and carbohydrate units and with an interior of the cells,which is a diluted aqueous suspension. These facts seems to indicate, thatthe prebiotic biosynthesis, the metabolism and a genetics were establishedto some extent, before the life were established. E.g. the central enzymein Glycolysis/gluconeogenesis, Triose Phosphate Isomerase may have beenpresent in the proteome [48]. And the very fist step in polymerization of car-bohydrates in the metabolism, the synthesis of D-fructose-1,6-bisphosphatefrom dihydroxyacetone phosphate and D-Glyceraldehyde-3-phosphate is con-trolled by a stereo specific enzyme, Aldolase [49]. An enzyme which also canbe identified as an ancestral enzyme [50].
The missing link between a saline prebiotic environment and LUCA isthe advent of life: a cell with a membrane, metabolism and genetics. A cell,who although it was unstable, was self generating, whereby a wave of lifewere started. 6ne might object, that the hypothesis about the emergence of homochi-rality in a prebiotic saline aqueous environment is speculation, without apossibility of verification. This is , however, not correct. Some part of thehypothesis can be experimentally verified. It is straight forward possible totest for homochiral stability of enzymes with respect to the activity of water.The prediction is that the homochiral stability of enzymes depends on the de-gree of salinity of the aqueous suspension. One shall expect, that an enzymein pure water is more chiral unstable than in an in vitro cytosol solution, andthat it is stable at a higher ionic concentration than in the cytosol.The hypothesis is also, that the stability of homochirality in proteins isa necessity for obtaining and maintaining the homochirality of the carbohy-drates [40]. It might also be possible to verify this part of the hypothesis:That the metabolism only acts with stereo specific enzymes, whereby thehomochirality of carbohydrates is ensured by the kinetics in the metabolism[40]. The prediction is that also Ribose’s metabolism is controlled by stereospecific enzymes, which ensures a D-Ribose wold, a necessity for RNA andDNA. And that these enzymes are ancestral and present in the Progenoteand in LUCA. If so, it establish an order in the evolution [40], and these be-haviours together links the physicochemical state of the cytosol in the livingcell together with the instability of homochirality and the dead of a livingorganism in the global wave of life.And it gives an ideas of, where in the aqueous environment and how theprebiotic self-assembly took place.
5. Acknowledgment
Jeppe C Dyre is gratefully acknowledged. This work was supported bythe VILLUM Foundations Matter project, grant No. 16515.
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