Anton Markoš, Charles University, Faculty of Sciences, Praha, Czech Republic
Keywords
Life, definition of life, abiogenesis, theories of life origin, metabolism, genetic code, complex systems, planetary dimension
1. Introduction
1.1. What is life?
1.2. Rules of the game
2. The playing-field
2.1. Where on Earth?
2.2. The source of organic carbon
2.3. Energy and metabolism
2.4. Descent of enzymes
2.5. Origins of the genetic code
2.6. Complexity
2.5. Emergence of cells
3. The “conquest” of the planet
Abiotic: Coming into existence by a process not communicated by living beings.
Cell: The basic element of all living beings endowed with genetic and epigenetic memory. A cell can come into existence only by a process of fragmentation of another cell. All cells are, genealogically, derived from LUCA; the lines of descent, however, are not straight due to frequent mergers between lines.
Central dogma: The statement that information flow in cells is unidirectional, i.e. from nucleic acids to protein, but not in reverse.
Creationism: The belief that life came into existence through the action of a supernatural being.
DNA (deoxyribonucleic acid): The digital genetic memory of the cell. Chemically, a nonrandom polymer of four types of bases (deoxyribonucleotides, nicknamed A, C, G, T). The linear sequence of bases can be compared to a message written in four letters. Due to the complementarity of bases (A-T, G-C), a DNA string can be copied into a complementary string of either DNA or RNA. DNA molecules exist in the form of a double helix of two complementary strings, which become partially separated only in the processes of replication or transcription.
Electrochemical potential difference: A form of energy resulting from unequal distribution of ions across a barrier (e.g. impermeable membrane).
Eukaryotic: Of a cellular type that is characteristic of animals, plants, fungi, or protists.
Evolution: The continuous appearance of novelties, usually marked by an increase of complexity, within genealogical lines. In neo-Darwinian theory the progeny will give rise to a set of individuals differing in genotypes. Confronted with the environment in the process of natural selection, the only genotypes that will contribute to the next generation are those which build (in the given environment) the fittest phenotypes.
Evolutionism: The doctrine that extant life evolved gradually from living entities of a lower level of complexity.
Fermentation: Performance of oxidation which generates electron acceptors during the process. The energy released is coupled to a synthesis of high-energy phosphoesters (e.g. ATP).
Gene: For the purpose of this review, that string of DNA which will be transcribed into RNA.
Genome: A species-specific set of genes organized in a characteristic pattern on the string(s) of DNA.
Genotype: A version of the genome. Genotypes differ not in the overall set of genes and their localization in the genome, but in that they contain different versions of homologous genes.
Life: The common feature of all living beings on this planet, best characterized as a list of properties which, as a whole set, never can fit any nonliving object. Living beings are characterized, for example, by uninterrupted evolution, common descent (through LUCA), cellular organization, genetic and epigenetic memory.
LUCA: Last universal common ancestor. A hypothetical being which stood at the root of all lines leading to contemporary organisms.
Optical activity: Result of handedness of branched molecules.
Panspermy: Theory explaining the existence of life on the Earth as a result of fertilization by germs coming from outer space.
Phenotype: All properties of organisms which are not genetic information.
Prokaryotic: Bacterial or archaeal.
Protein: Primarily, a nonrandom string of 20 amino acids synthesized in the process of translation. Thus, the sequence of amino acids more or less corresponds to the sequence of bases in the gene. The protein molecule may subsequently undergo extensive chemical modifications. The functions of proteins include catalysis of most chemical transformations in the cell, information processing, and acting as the building blocks of structures.
Replication: Synthesis of a complementary strand of DNA according to a pre-existing string.
Respiration: In molecular terms, performance of an oxidation-reduction process and coupling of the energy released with pumping protons across the membrane.
Ribonucleoprotein: A complex of protein(s) and RNA(s).
RNA (ribonucleic acid): A nonrandom polymer of four types of bases (A, C, G, U) synthesized as complementary to a gene. One class of RNAs (mRNA) mediates the translation of the sequence of bases in the gene into a sequence of bases in protein. Other classes of RNA participate in cellular functions in complexes with protein.
Transcription: Synthesis of an RNA string complementary to the gene.
Translation: Proteosynthesis, the process of decoding the message written in the 4-letter code in RNA (mRNA), into a 20-letter code of protein.
Vitalism: Teaching that maintains that in order to describe living processes, forces (laws) beyond those known in physics and chemistry should be sought and defined.
Life is a phenomenon which emerged on this planet as a result of very specific constellations of events. Cellular life emerged about 3.8 Ga ago as the outcome of many hypothetical steps: abiotic syntheses of organic compounds, protometabolism, the emergence of replicators, insulation into membranous compartments, etc.; the most enigmatic among these events is the establishment of the genetic code. During most of evolution, the planetary dimension of life (represented by prokaryotic cells) prevailed, followed by the appearance of multicellular eukaryotes in the late Precambrian.
The enigma of life’s origin remains one of the most challenging problems of contemporary science. However clumsy the definition of life may be, we shall agree that “it” has a beginning and an evolution. Extensive research into geological and historical vestiges takes place, and sophisticated logical, computational, and chemical models have been built in the hope of revealing the mystery. In spite of many years of research and enormous progress, the answers available today remain as unsatisfactory as those of seven decades ago, when Oparin proposed the first scientifically formulated theory. Due to the paucity of concrete evidence concerning the early conditions on the Earth (and various planetary sub-compartments), even the simplest experiments aimed at understanding the early steps towards life remain biased by many uncertainties. As a result, interpolations made between the outcomes of such experiments on the one hand and contemporary life on the other quite often go beyond what is acceptable in established experimental sciences. After all, the problem transcends the scope of the experimental sciences, which aim to reveal regularities, “laws,” and general principles. Historicity, singularities, and extrapolation to unusual scales of space and time never make the situation easy for them. A further source of difficulties in such a transdisciplinary project may lie in the absence of a common language among the sciences. Planetology, biochemistry, biology, the science of complexity, thermodynamics, geochemistry, etc., each project their own view of affairs, but the superposition of these views is far from being satisfactory: many loose ends remain to be interconnected, many should be abandoned, and even more need to be invented.
Difficulties begin with the attempt to define the very subject of our investigation – life. Even the most respectable dictionaries restrict themselves to vague definitions such as “a common property of living beings that makes them different from non-living objects (!), enables them to feed, grow, breed, etc., and becomes lost after their death.” Some encyclopedic sources openly resign the task and simply provide a list of life’s attributes. The same holds true for biology textbooks: no definition draws a satisfactory distinction between life and non-life, life and mechanisms, life and “intelligent” machines, life and complex systems that undergo evolution, etc. The main difficulty may reside in the fact that the definition should somehow incorporate structures and events occurring simultaneously at many spatial and temporal levels: it may be that our language does not allow us to encompass them correctly.
A common attempt to escape such philosophizing and to remain firmly in the realm of science is to confine oneself not to life, but to the term organism. The meaning of this word, however, is also very vague, and has oscillated wildly during the last 200 years. At one pole we have a Kantian entity, which is an “organic product of Nature.” In contrast to a mechanical device (a machine), such an entity is its own cause and effect, endowed not only with movement, but also with self-building forces, and with purpose; that is, it can take care of itself. At the other pole, the term is a mere synonym for mechanism. Authors operating with the term organism usually do not bother with explanation. The reader is, then, left with fuzzy definitions like the following, extracted from a few popular encyclopedias: “Any living thing”; “An organized body, consisting of mutually connected and dependent parts constituted to share a common life; the material structure of an individual animal or plant”; “A form of life composed of mutually dependent parts that maintain various vital processes.” Such definitions will, of course, easily encompass machines, ecosystems, the biosphere, and even dead bodies, and the nature of “vital processes” will remain undefined. (On the other hand, one of the definitions excludes fungi, protists, and bacteria.) Are there forms of life that are not at the same time organisms? We are left, as Kant was, with a mere list of properties: cellular organization, metabolism, genetic memory, homeostasis, and so on.
A.G. Cairns-Smith has introduced a good operational definition of both the organism and life: An organism is that which can take part in the processes of evolution through natural selection. For this it must have a dual constitution, namely: (i) a store of genetic information … [and] (ii) ... phenotype. … Life is an informal term for the seemingly purposeful quality of evolved organisms. If organisms are prerequisites for evolution, ‘life’ is rather a product of that process. This definition allows us to uncouple the evolution of “non-living” organisms from the commonly accepted attributes of extant life (see below). It includes, however, two a priori assumptions that may simply reveal an idiosyncrasy of our times: the genotype-phenotype dualism and a belief that all evolution can be reduced to the selection of molecular replicators.
A competing view can be summarized by the holistic slogan coined by M-W. Ho: “Life is a process of being an organizing whole”. This view emphasizes the fact that life is a process coherent over a vast range of spatial and temporal scales. The whole body (be it a cell, a multicellular organism, or even a more complex being) is thus “informed” across all space and time levels; information as well as energy is “non-local”, but is shared by the whole body. Such a non-reductionist approach is somewhat alien to the discourse going on in contemporary biology. I feel, however, that it is necessary also to stress the interconnectedness of all hierarchical levels, with concomitant independent (and emergent) behavior at each of them.
It is beyond hope to discuss here all the ideas connected with the appearance of life. Our thoughts will be confined to some scenarios plausible within the frame of the experimental sciences; no creationist versions of the origins of life will be discussed. Furthermore, we shall suppose that the Earth was the cradle of cellular life forms, i.e. that life appeared as an indivisible part of the evolution of our planet. The theory of panspermy, which assumes that germs were brought to the planet from outer space, will not be taken into consideration. We shall also leave aside speculations both about possible different forms that may reign somewhere in the Universe, and about man-made creations (e.g., Artificial Life). Even after such a pruning, we will be left with many difficulties linked to the very definition of life. We shall make the further assumption that cellular forms of life have originated on the planet only once, i.e. we suppose the existence of the Last Universal Common Ancestor (LUCA). This assumption is reasonable because life’s origin is highly improbable anyway, hence the whole event can be considered a singularity. Moreover, only a narrow time-window may have existed in the evolution of the planet during which conditions were favorable enough for the event to occur. Finally, the origins of life might have been impossible in the presence of other (competing because more highly evolved) forms of life.
· We have to face uncertainties regarding the early history of the Earth. Except for common agreement as to the Earth’s age - about 4.5 Ga - the available scenarios concerning its evolution may considerably differ. How much organic carbon was brought in by planetesimals, and what fraction of these compounds survived the initial warming of the planetary body? Was the planet completely molten or only partially so? How complete was the primary fractionation of elements? How much organic carbon was brought in during the cosmic bombardment that followed? What was the composition of the primordial atmosphere, hydrosphere, lithosphere, and what was the subsequent evolution of the planetary surface? What was the nature of prebiotic syntheses, and how did they become enchained into the body of LUCA? All these questions bring too many degrees of freedom into the game.
We shall accept the opinion that 3.8 Ga old fossils found in the Isua formation (Greenland) represent fossils of genuine prokaryotic cells, i.e. we shall assume that life that was more or less comparable to contemporary life had established itself by that time. “Comparable” means that:
· It was already bound to the existence of cells and probably far away from LUCA
· It ruled over a genetic memory based on DNA, and over a cellular “executive” based on proteins
· Its metabolism (including photosynthetic assimilation of CO2) was fuelled by free energy of oxidation-reduction couples. Energy was transformed into two universal and mutually convertible energy currencies of the cell: (1) difference of electrochemical potentials of ions across a membrane, and (2) energy of chemical bonds in a “macroergic” compound – usually a molecule of ATP, but other organic phosphoesters and pyrophosphate are also acceptable. Energy liberated from these sources (by discharge of the difference of electrochemical potentials, or by splitting high-energy bonds) could be coupled to all processes requiring energy.
· The oxidation-reduction couples were – by means of biogenic photosynthesis – already connected to, and boosted by, the incoming energy of solar light.
The evolution of life has from the very beginning been both a molecular and, at the same time, a planetary phenomenon: the totality of the process cannot be described and understood from any single level of description. The planetary dimension of life (see Earth as an Abode of Life) tends to be rather neglected. Moreover, there is a large gap in the study of life history. Investigations into the origins of life tend to be concentrated upon the relatively short initial period of planetary history, whereas evolutionary theory is highly focused on multicellular eukaryotes, i.e. on the last half billion years. The period of three billion years in between attracts little attention – and yet this, the longest period of life evolution, is notable for its planetary dimension. During this period, enormous work was invested in rebuilding the planetary surface, and firm grounds were established for planetary homeostasis to become controlled, as I believe, by biotic factors (see Earth as an Abode of Life). The evolution of the planet and the evolution of life go hand in hand from the very outset, and a deeper insight into the processes that mold this co-evolution should cast more light on the very beginnings of this relationship.
For life, as for all historical phenomena, it is the case that the present state is an outcome of many possible (or thinkable) trajectories. The “real” one is only to be guessed and tentatively reconstructed not only from extrapolations based on present forms of life, but also from interpretation of paleontological and cosmological vestiges. The interpretation of such vestiges is by no means unequivocal, and several competing and mutually exclusive interpretations are in circulation at present. In this part of our discussion, we shall focus our attention on factors recognized by contemporary science as basic prerequisites for the origin of life: the sources of organic carbon and of energy (and of their development), the emergence of the genetic code, the emergence of complexity through evolution and, finally, the emergence of cellular life.
What was the putative “biotope” which enabled life to establish itself? For the pioneers of abiogenic theories, the open ocean seemed to be an obvious candidate. Its masses, according to their views, served as a reservoir of organic matter (“primordial soup”, whatever its origin was, see the next section). An enormous body of evidence has since been accumulated in favor of many different locations, e.g. evaporating lagoons, fresh-water reservoirs, active surfaces of various kinds, hydrothermal vents, melted base of glaciers, aerosols, water, percolated deep layers of the crust, etc. Salinity, high (or low) temperatures or pressures needed for catalysis, the presence of active surfaces or of special configurations of catalytic matrices, solar radiation or the absence thereof, oxidation–reduction potential, and many other factors have been proposed to support or refute particular hypotheses. As all such niches existed in parallel, a “division of labor” cannot be ruled out either. Mainstream life (from LUCA onwards) can be easily considered as a merger of different parallel prebiotic processes. Multiple streams leading to cellular life may have originated in different environments, each contributing to different aspects of the emerging life. Perhaps the single common denominator to all theories is the essential precondition of the presence of water in a liquid state.
Contemporary life is tightly coupled to the existence of very complex organic compounds. At the surface layers of the contemporary Earth, the most frequent form of carbon is CO2 and/or carbonates; most deposits of organic carbon present in the Earth’s crust are usually interpreted as fossilized remnants of living beings. The synthesis of organic compounds is totally ensured by living beings, phototrophic or chemolithotrophic. No known mechanism (except human technologies, of course) can perform “abiotic” reduction of CO2 to organic compounds today. Was, then, organic carbon a necessary precondition for the emergence of life? If so, how did organic compounds appear on the abiotic planet? If not, what were the first “inorganic” forms of life?
Most theories of the origin of life consider the presence of organic compounds as indispensable from the very beginning, i.e. they hold that the presence of organic compounds must have preceded the origin of life.
· The original supply of organic compounds could have originated in space, and been brought to the planet during the accretion process. It is well known that chondrites (a type of meteorites) contain substantial amounts of a wide assortment of organic compounds; the presence of a great variety of organic compounds in large quantities has also been confirmed (by spectroscopy) in outer space. Estimates of the contribution of this cosmic store to the birth of life vary considerably, depending on the model of the early evolution of the planet adopted. Some authors assume that upon accretion the Earth became molten, which would necessarily destroy any organic compound originally present. Even if that were the case, organic compounds could have been brought in during a subsequent phase of extensive “bombardment” of the planet by planetesimals.
· Recently, however, the molten Earth postulate has been put in doubt, and T. Gold has coined a theory assuming huge deposits of organic carbon of cosmic origin. According to the theory, hydrocarbon (mostly methane) deposits at depths of 100-300 km, existing up to the present, gave rise in the past to most “fossil” fuels (petrol, gas, anthracite, kerogen), and also supplied the emerging life with both building blocks and energy with which to run organic syntheses.
Another set of theories explains the origin of organic compounds as beginning with an “inorganic” Earth, with atmospheric carbon as a source.
· Originally, it was assumed that the primordial atmosphere was highly reducing, containing compounds like methane, ammonia, water, hydrogen, hydrogen cyanide, etc. It was shown experimentally that electric discharges in such mixtures lead to synthesis of a broad variety of organic compounds, i.e. carboxylic acids, amino acids, formaldehyde etc. However, no nucleotides – the building blocks of nucleic acids – and no organic compounds containing phosphate were obtained. According to this scenario, after some time, the oceans would contain a mixture of simple organic compounds (“primeval soup”), and chemical interactions among them would establish some kind of primitive metabolism leading to building blocks of living beings.
· Recently it has been commonly accepted that the primitive atmosphere was only mildly reducing, consisting mainly of CO2, nitrogen, and water. In such a mixture, electric discharges are not energetic enough to reduce CO2; therefore, a photoreduction driven by UV photons, with ferrous ions as electron donors, has been postulated. (Such a mechanism would also explain the enigma of the origin of banded iron ore deposits.) This process would also lead to a “soup” of a kind.
There exist also “no soup for starters” scenarios:
· One approach proposes the concomitant unfolding of primitive metabolism and CO2 assimilation, usually on two-dimensional surfaces of some sort (a primeval “pizza”, to continue with the analogy), e.g. on the surface of pyrite crystals.
· Even more radical is the theory originated by A. G. Cairns-Smith. He suggests that the first organisms were inorganic, self-replicating crystals. In this case, the first evolution may or may not have been accompanied by the accumulation of organic compounds: organic syntheses may have appeared only later, as processes catalyzed by already present, evolved crystal organisms. Cairns-Smith uses the analogy of building a stone arch. You need a scaffold to build it, but when it is complete, you will not easily decipher the nature of the scaffold. In this analogy contemporary replicators and DNA/protein represent the arch, whereas self-replicating clay crystals are the long-abandoned scaffold.
The metabolic driving force in living beings comes from the free energy released during oxidation-reduction reactions (halobacteria present the only minor exception from this rule). The energy yield of a particular reaction can be estimated, e.g. from the standard reduction potentials (DE°’), and calculated if the actual concentrations of reactants and the reaction conditions are known. Some examples of oxidation-reduction couples, which are in use in contemporary living beings, are given in Fig. 1.
[Fig. 1. The scale of standard oxidation-reduction potentials DE°’ for some half-reactions (-0.414 for 2H+/H2, +0.815 for 1/2O2/H2O) of a redox couple. Energy can be extracted when electrons flow from the more negative to the more positive member of a couple. The lengths of arrows give an impression of the energy yield of some couples. The highest energy yield can be obtained from aerobic respiration, where electrons flow from organic matter to oxygen; the yield is minuscule when organic matter is oxidized by protons. The driving force for reverse flow of electrons is provided by photons. For oxygen-free conditions that reigned on the prebiotic Earth, the most plausible couples are “chemolithotrophic“ ones: with electrons flowing from, e.g. hydrogen, Fe2+, Mn2+, SH2, or methane, to, e.g. sulfate, nitrate, Fe3+, uranyls, and so on. Abbreviations for organic compounds: Fum – fumarate, Suc – succinate, Lac – lactate, Pyr – pyruvate, GAP – glyceral-3-phosphate, PGA – 3-phosphoglyceric acid, Ac – acetate, 2-OG – 2 – oxoglutarate.]
Even from the very beginning, coupling of the planetary redox cycles to solar energy may have occurred. Very probably, reduction of CO2 by ferrous ions took place, driven by ultraviolet light. If such a system came to work, it could have become independent from the possible limitations of either donors or acceptors of electrons. Redox couples would be produced at the expense of solar energy, as in the contemporary biosphere.
A special kind of redox reaction is dismutation, where two identical molecules become mutually a donor and an acceptor of electrons. From the viewpoint of life origin, dismutation of sulfide (S2-) to pyrite (S-) and sulphur (S0) may, according to some scenarios, have played a crucial role as an energy source for the prebiotic biosphere.
A further redox couple may be created in the process of fermentation – the decay of certain specific organic compounds. Here, electrons from the donor molecule are first transferred to an auxiliary acceptor, and the reduced molecules, upon metabolic transformation, give rise to a final acceptor of electrons. Hence, the reaction does not require an exogenous electron acceptor, because it is generated in the process itself. A classical example of the process is alcohol fermentation in yeast: glucose is oxidized and transformed to pyruvate, which will, in its turn, accept electrons to become reduced to, for example, lactate or alcohol. Fermentation, however, is bound to the presence of a special kind of organic molecule (e.g. sugars), which may not have been present in the prebiotic world.
Redox reactions, conceivable for the prebiotic planet, must have lead to dissipation (thermalization) of the chemical energy stored at the planet and/or accumulated by the action of solar radiation. The emergence of life would – by increasing the efficiency of catalysis – enhance such processes, and create new ones. Part of the energy liberated would, however, be temporarily intercepted and “stored” in complex chemical compounds and structures comprising living bodies. This faculty is not confined to life only: so-called dissipative structures (e.g. gyres, flames, fountains) can intercept, and even greatly facilitate, the energy-decay processes they depend upon, while increasing their internal complexity (by decreasing their entropy at the expense of ever-increasing and continuous entropy production in the environment). From this viewpoint, life is a complicated and long-lived dissipative structure; it cannot, however, be fully explained away as such. The main difference is in the genetic memory typical of life (see below).
As already stated, the energy extracted from redox reactions can – in the contemporary biosphere – be transformed into two universal forms of potential: energy of chemical bonds stored most frequently as ATP molecules, or electrochemical potential of ions (mostly hydrated protons). The former reaction can take place in a homogeneous space, as an outcome of redox reactions accompanied by formation of high-energy intermediary thioesters and phosphoesters. Energy liberated by splitting these bonds can be coupled with phosphorylation of ADP to ATP (Fig. 2a). Fermentation is a typical reaction of this kind. It is important to note that the reaction has a strict stoichiometry (one ATP for each thioester bound), and requires sophisticated enzymatic machinery and intermediates.
The second universal form of cellular energy is the driving force generated by the difference of electrochemical potentials of ions across a membrane. In contemporary organisms, this difference is generated by a chemiosmotic process localized into a membrane (Fig. 2b). The transfer of electrons between the oxidized and the reduced part of the redox couple is channeled through a membrane structure – the respiratory chain, or an analogous redox machinery coupled to the photosynthesis. The energy liberated by electron flow is connected to pumps translocating ions (mostly protons) across the membrane: a difference of electrochemical potential of the particular ion will be generated across the membrane. This potential can, beside other functions, drive the reaction of ATP synthesis, via ATP synthase located in the very same membrane (Fig. 2c). There is no fixed stoichiometry of electrons transferred per number of protons pumped: The efficacy of proton translocation depends on the energy charge of the redox couple in use (see Fig. 1). Even negligible energy yields (e.g. oxidation of organic matter by CO2) can sum up to a reasonable life-driving potential.
[Fig.2. Generation of energy stores, and localization of the processes, in contemporary cells. (a) The process of fermentation produces, as intermediates, phosphoesters of organic compounds (X – organic moiety, P – phosphate group, ~ delineates “energy-rich” bond. Phosphate and pyrophosphate may stay for ATP in some reactions). (b) Respiration: a membrane-confined redox process coupled to a proton (H+) pump. An electrochemical potential of protons across the membrane is generated. A similar process is at work in photosynthesis where the redox process is driven by high-energy electrons excited by photochemical processes. (c) The potential can be released by driving ATP synthesis via ATP synthase localized in the same membrane. The process can be reversed: electrochemical potential can be generated at the expense of ATP generated, e.g. in the fermentation process.]
Through the complex of the ATP synthase, both energy stores are mutually interconvertible: the complex can also be used to pump protons across the membrane at the expense of ATP. Both potentials provide a driving force for all other forms of cellular work (chemical syntheses, maintenance of chemical composition of different compartments, transport across membranes, motility, heat production, chemiluminescence, etc.).
How did one energy source or the other come into existence, and which of them was primary? As many authors consider homogeneous conditions more primitive, a lot of effort has been focused on deciphering the predecessor of “substrate phosphorylation” taking place in fermentation (Fig. 2a). The reconstruction of events usually starts with homogeneous solutions (a “primeval soup”) containing fermentable compounds (e.g. sugars) accumulated abiogenetically. These would be transformed, via thioester compounds, to a final compound bearing high-energy phosphate group (e.g. pyrophosphate). Laboratory simulations of such a scenario are, so far, not persuasive. Abiogenesis would lead to a mixture of thousands of different fermentable species in low concentrations. In addition, optically active compounds (e.g. sugars, amino acids) would come in racemic mixtures, in contrast to biogenic products, which prefer one of the possible enantiomers (e.g. D-sugars, L-amino acids). Bringing such heterogeneous mixtures to a common product would be a precarious task even for a battery of contemporary enzymes, let alone for the inefficient catalysts assumed to be present in the prebiotic soup. There is no satisfactory concept available concerning the nature of putative thioester intermediates, nor that of the final “energy-storing” molecule.
A modification of this scenario supposes the presence of catalytic surfaces containing, for example, sulfides or pyrite in contact with the soup. Such surfaces would adsorb some components of the soup, thus ensuring selective catalysis and canalizing of intermediates (see below).
Some proponents of the soup theory (including Oparin himself) have recognized the need to confine the first biochemical reactions into compartments. They therefore propose the existence of membrane-bounded compartments insulating the internal space from the surrounding medium, at the same time allowing exchange of nutrients, energy, and entropy. As to the components constituting the membrane, both organic (lipids) and inorganic (e.g. sulphide gels) materials have been suggested. In the presence of membrane, however, electrochemical potentials of various kinds should also be taken into consideration as a primary energy source. At the beginning, they may have arisen simply by compartmentalization of some redox reactions (e.g. iron II oxidation, Fig. 3), followed later by active pumping. Synthesis of high-energy compounds by membrane-independent pathways may be a late process, arising only after the synthesis of fermentable compounds has come under cellular control.
[Fig. 3. Photochemical oxidation in a membrane-bounded compartment of ferrous ions by protons. Whereas hydrogen molecules can freely leave the compartment, the membrane is impermeable to protons. Hence, the interior of the compartment becomes depleted of protons and an electrochemical potential of protons across the membrane will become established.]
It is also conceivable that both contemporary cellular energy potentials developed only in the later stages of prebiotic evolution. If, for example, the cradle of life lay in the deep layers of the Earth’s crust (“deep hot biosphere”, see below), high temperature and pressure, together with abundant catalysts, may have driven (and canalized) a whole set of prebiotic syntheses that are unknown in today’s organisms.
Metabolism, i.e. an orderly network of (mostly) controlled chemical reactions present in contemporary organisms, requires as a prerequisite the existence of efficient catalysts – enzymes. These, however, are only latecomers in evolution, being proteins or ribonucleoproteins (proteins plus RNA). To reconstruct their predecessors is therefore an extremely urgent task.
Both contemporary proteins and RNA are nonrandom linear polymers (of amino acids and nucleotides, respectively). Random synthesis from precursors is inconceivable: the “sequence space” becomes astronomical even for rather short strings, and random polymers are extremely inefficient in their capacity to catalyze anything. The shape of the molecule, on which its function depends, is tightly dependent on the primary sequence. Functional protein strings, however, are incapable of self-replication. In contemporary organisms, the information determining the amino acid sequence of proteins is stored in cellular genetic memory. To simplify our analysis we will pay attention only to that part of genetic memory which resides in the molecule of DNA. Protein synthesis takes place in a complicated procedure involving (1) transcription of the relevant part of DNA (the gene) into RNA; (2) processing of RNA; (3) translation; (4) processing and localization of the newly synthesized protein. The whole process requires a molecular machinery consisting of hundreds of proteins and/or ribonucleoproteins. DNA itself is metabolically passive: its replication requires elaborated protein machinery (coded by DNA). Such an interdependence of memory storage and executive (the chicken-and-egg problem) clearly indicates for some authors that the system became established long after metabolic pathways came into existence. How, then, did metabolism begin?
One attempt to solve the paradox is the proposal of the so-called “RNA world.” The molecule of RNA can serve as a template for self-replication (more precisely, of replication into a complementary chain). In contrast to DNA, however, RNA molecules can give rise to very complicated shapes, and, even in contemporary RNAs, some can fulfill limited catalytic tasks. The theory assumes that RNAs (or populations thereof) could have existed that could accomplish the catalysis of self-replication and, at the same time, of some special metabolic reaction.
M. Eigen provided one possible solution to the puzzle: he proposed a model of a hypercycle (Fig. 4). If a set of replicators–catalysts becomes confined into an enclosed space, they may share both metabolites and the efficacy of the replication. Such a team will evolve as a single unit toward higher efficiency and specialization of the team’s replicators-catalysts. Gradually, metabolic pathways become established, and the information storage will also become separated from the catalytic functions.
[Fig. 4. Hypercycle. (a) Replicators Ii autonomously ensure their own replication. Besides this ability to replicate, each of them is endowed with some auxiliary function, e.g. catalysis of a particular reaction. (b) If a set of replicators becomes confined (e.g. by a membrane) in common space, the elementary catalytic reaction provided by one member of the set may help the replication of others, and vice versa. Such a team of replicators – the hypercycle - has an advantage compared to isolated replicators in an open space: the metabolites are present in much higher concentrations than outside, and can be shared by all replicators. The probability of efficient propagation of all members of the team will increase. (c) At this point, Darwinian evolution can begin: Multiple copies of each of the replicators can undergo various mutations, and those which – via increased cooperation in the team – can increase their own replication will prevail in the team. Evolution will become a matter not of isolated replicators, but of a whole hypercycle. If autonomy from the environment is retained, evolution will lead to continuous specialization of members of the set. Even the replication itself may become the business of some specialized members.]
The critics of the “RNA world” concept point out, first, that there is no experimental or even speculative model of abiotic emergence of nucleotides, the building blocks of RNA. Many attempts have therefore been made to find a polymer of simpler monomers (whose presence in the prebiotic soup is more conceivable), that might be able to store information, to be catalytically active at the same time, and to evolve gradually into RNA. Moreover, contemporary RNAs are able to catalyze only a limited set of reactions. It may be, of course, just a matter of time before we discover reactions that would take the edge off both criticisms. Even then, however, the transition from the RNA world into contemporary dualism of nucleic acid and protein is by no means a simple task to explain (see the next section).
In contrast to nucleotides, the appearance of some simple amino acids, and even their random polymerization in the prebiotic soup, is quite feasible. Some such random peptides bear catalytic properties: the only problem, then, is to explain the selection of the correct peptides from the astronomical number which are junk. Some investigators therefore assume selective assemblies of peptides, in matrices provided by other proteins or inorganic or organic colloids and/or surfaces. In the account that assumes the deep hot biosphere, such matrix-environments (which would be, moreover, much more stable than in surface waters) would also be cooperative due to their high temperatures and pressures, and the abundance of transition metals (V, Mo, Mn…), which may have dramatically helped to boost the prebiotic syntheses. Finally, S. A. Kauffman argues that the “catalytic task space” comprising all the necessary reactions may be covered by some 108 different catalysts: however high the number, it is finite. Provided that some kind of organization (matrices, membranes) compartmentalized such a system, it could have been capable of primitive metabolism.
The discovery of the genetic code and the establishment of the “central dogma of biology” on the one hand, and the neo-Darwinist synthesis on the other, has brought to the fore the origins of the genetic code as a central point in deciphering the enigma of life’s origin. We saw in the previous section that protein molecules cannot be copied. They must be synthesized according to information stored in DNA. DNA molecules, for their part, can be copied with great accuracy (such molecules able to serve as a model for producing identical copies - replicas - will be referred to as replicators), but the process of their copying is by no means spontaneous – it requires a very sophisticated machinery consisting of hundreds of proteins. The origin of the scheme “all information in DNA - all power in protein” is indeed a very difficult enigma to solve. Of course, the simplest solution would be a “self-replicating replicator”, and this is a direction in which many efforts have been aimed.
It should be pointed out that neo-Darwinian evolutionary theory supposes that evolution (of organisms as we know them today) by natural selection can, in principle, be reduced to evolution of replicators, i.e. mostly DNA in contemporary forms of life (see Evolutionary Mechanisms and Processes). All characteristics of living bodies (the phenotype) are encoded in the information stored in the replicator (the genotype); the better a phenotype copes with its environment, the higher the capacity to produce replicas of its information molecule. The fitness of a replicator is a measure of its capacity to become a forebear of other replicators. As the resources (building material, energy) are always limited, the fraction of fitter phenotypes, i.e. those better adapted to a given environment, will become ever greater in each subsequent generation, whereas the less efficient phenotypes (and their replicators) will gradually become extinct. This would quickly lead to an equilibrated population containing the best-adapted organisms. The ever-changing environment will, however, continuously change the criteria of fitness. Moreover, errors occur randomly in the replicator molecules, supplying the population with new versions of genotypes. As any step attained is practically irreversible, the whole process of evolution is cumulative: a new generation of progeny starts from the level attained by the parent(s). It is the existence of memory that makes life so extraordinary, compared to simpler dissipative structures.
The question of how such a dual system could have emerged during prebiotic evolution thus became central for evolutionary biology. “Protein first” and “DNA first” scenarios can easily be ruled out, and investigations have become focused on a search for some kind of self-perpetuating replicators that could have evolved by natural selection and, when the time came, transformed into the contemporary DNA-protein model. Self-perpetuating catalytic RNA (see above) would solve the problem only partially. Even if an RNA world did exist (and the model is very plausible, see previous and next section), it was an intermediary state, not the beginning.
One category of efforts is aimed at finding self-replicating molecules based on some kind of “protonucleic” acids. Usually, simpler substitutions for the ribose-phosphate backbone and for some bases are sought, but no feasible prebiotic scenario has been proposed so far. Another line of thought is centered on the possibility of inorganic replicators, with the copying process driven by the chemical potential of the prebiotic environment. In that case no replication cycle would be necessary: simply a class of self-replicating inorganic molecules (non-living organisms) would appear on the Earth. Ever-present clay minerals seem to be the best candidates for such a function. They grow readily in aqueous environments, their crystal lattice can contain various inhomogeneities that will be perpetuated in subsequent layers as the crystal grows, and “progeny” can be generated simply by breaking away parts of the growing crystal. These non-living “organisms” can be submitted to natural selection, i.e., with time, qualitative shifts can occur in the population of crystals. For the inorganic scenario, the biggest challenge is to explain the transition, the takeover by organic molecules. Contemporary complexes of organic material with inorganic crystals (e.g. humus or kerogen) allow speculations to be built upon, but no breakthrough has been achieved so far.
The emergence of translation also requires a plausible explanation. The current scenarios are centered on aminoacyl-RNAs or RNA-oligopeptides, analogous to contemporary tRNA-peptides. Such compounds could greatly increase their catalytic, i.e. self-replicating, power (especially when combined with coenzymes). If confined to a compartment and ordered (e.g. on crystal surfaces), they may have produced big ribonucleopeptides. The division of labor may further have led to the establishment of a DNA genome on the one hand, and of a genuine translation on the other, with RNAs being part of some systems. There is no need to emphasize that very few details of such a scenario have been provided so far.
As already stated, most of the current theories of life’s origin are based on neo-Darwinian theory. In this framework, selection is the single source of order (absence of selection means decay), life processes are controlled by genetic program (taken as an analogy of a computer program), and organisms are the results of contingent tinkering, i.e. they are constrained by their history.
Investigations in the realm of macroscopic systems, together with mathematical models of behavior of complex dynamic systems (of which life is only a single example), drew attention to the fact that in such systems there is nothing like a “basic level of description” from which processes could be fully explained. Each level of description displays emergent properties, not easy to grasp from other levels. From this point of view, life is, and also began by being, whole and integrated: it was never disconnected and disorganized. Hence, life started as a collective property of complex systems of catalytic polymers and of molecules whose reactions are being catalyzed. Mathematical models show that complex systems may evolve in three ways. Two of them are not interesting: the system either reaches equilibrium (“freezes”) or disintegrates in chaos. The third possibility, however, means continuous evolution at the narrow edge between order and chaos.
But how could such abstract mathematical relationships become implemented into material bodies as living beings? It seems that the repertoire of possible molecular shapes is very large (of the order of 106-108), but, in any case, finite. Different molecules can have the same local shape: therefore, a set of randomly formed catalysts that can cover all functions in a given catalytic task space is conceivable. Such a dynamic network of catalysts does not require a genome to evolve: if conditions are favorable (e.g. providing a steady and sufficient supply of catalysts), it will maintain itself on the aforementioned edge between equilibrium and chaos, and become more and more complicated. Such a system may gradually develop both sophisticated control over its environment (homeostasis, well-defined metabolic pathways, sets of optically active metabolites), and the means to develop a medium in which information on the best catalytic molecules can be stored. The models developed so far are highly speculative, but scientifically feasible.
A point in the favor of such models is the very fact that in living beings there is hardly to be found, at any level of description, a constellation that is homogeneous, monotonous in chemical composition, in fabric, in behavior or in time; everything is highly structured. Furthermore, as mentioned above, the structures are mutually interconnected across many orders of space and time. Living systems never ceased to exist – their genealogy goes down, through 4 billion years, to the very roots of life. Given this, it is not surprising that different models, each stressing a very particular and limited area of the phenomenon of life and ignoring its historical quality, cannot satisfactorily explain life itself, much less its origins.
While partial steps in the evolution of life can be sometimes plausibly explained and even experimentally modeled, the crucial step in the affair – the origin of cellular organization - remains in almost complete oblivion. Brief characteristics of extant cells may help in understanding the difficulty of the task. Contemporary life is classified by most authors into three domains: bacteria, archaea, and eukaryotes. Common cellular characteristics can be summarized as follows:
· The cell is bounded by the plasma membrane, a boundary dividing the cytoplasmic space from outer structures and from the extracellular space. The layer of lipids makes the membrane impermeable to virtually all molecules except small non-polar (water, oxygen, CO2, N2, etc.) or lipophilic ones (e.g. steroids). Proteins inserted into the lipid membrane accomplish a selective trans-membrane passage of material and information between the cell’s insides and the outer world. Plasma membrane is the only membrane of many bacterial and archaeal cells, i.e. it is the site of all membrane-situated functions (e.g. respiration and chemiosmotically coupled ATP synthesis, photosynthesis, sensors, pumps, etc.); an elaborate system of intracellular membranes with a division of labor is present in eukaryotes. Due to the plasma membrane and the work carried out by its protein constituents, the cytoplasmic space differs from the space outside on almost all physical, chemical, and structural parameters. The membrane therefore ensures the autonomy and homeostasis of the cell.
· Every cell has its own oxidation-reduction machinery (usually both respiration and fermentation are present), which is coupled to creation of both mobilizable energy sources, i.e. electrochemical potential difference and ATP.
· Every cell has its own genetic apparatus, i.e. DNA genome located in chromosome(s), and devices ensuring replication of DNA, repair of DNA, transcription and proteosynthesis.
· The cell is able to grow and divide; its daughter cells will inherit all necessary structures, including a copy of its genome; extant cells came into existence through the division (and sometimes also merger) of pre-existing cells; no generation de novo from non-cellular material is possible.
· The plasma membrane delimits the boundary of the cytoplasm, but not of the cell itself. Cells build a sophisticated scaffold – the “extracellular matrix” (cell walls, shells, fibers, mineral deposits, etc.) which serves, for example, as mechanical support, shelter, metabolic compartment, or as a background for maintaining multicellular communities.
· Various sophisticated mechanisms enable cells to spread pieces of their genetic information to other cells. This system is especially well developed (and vitally important) in bacteria and archaea, which can exchange pieces of DNA by means of conjugation, transformation by exogenous DNA, or via various kinds of transmission vectors. In principle, there are no species barriers for such a gene market, and a great fraction of genes can literally be shared throughout the whole world. Eukaryotes greatly suppressed this system. Instead, they invented sexual processes whereby a whole genome is communicated (through specialized germ cells); the process is almost exclusively confined to individuals belonging to the same species.
· Cells are able to communicate with other cells, and form various kinds of functional (bacterial consortia, tissues, ecosystems) or morphological (multicellular body) assemblies.
· Cells of all three domains share so many characteristics that a common evolutionary origin is postulated, from a hypothetical “eocyte” cell type.
(A non-biologist should be warned that many exceptions to these rules can be found, due to specialization, parasitic or unusual lifestyles, etc. The characteristics listed above present the most schematic of reductions.)
The relationships between the three cell type domains are controversial. Usually, the hypothetical predecessor of the extant domains - the eocyte - is considered to be close to a common ancestor of both the eubacterial and archaeal domains (the recent discovery of so-called nanobacteria may throw more light on the reconstruction of ancient life forms). Later, presumably as late as 2 Ga ago, the eukaryotes appeared, as a result of the symbiotic merger of two or more bacterial and/or archaeal cells.
A counter-argument runs as follows: (1) If the RNA world ever existed, it could have existed only at a mild temperature (RNA is highly thermosensitive). Ribonucleoproteins in extant cells should be considered as the remnants of such an RNA world. (2) Ribonucleoproteins are abundant in eukaryotes, whereas in both bacteria and archaea they are drastically reduced. (3) The deepest branchings of the evolutionary tree of both bacteria and archaea contain hyperthermophiles, whereas no such organisms are present in eukaryotes. This leads to a scenario with eukaryotes as the closest heirs of the eocyte. Afterwards, the lines leading to bacteria and archaea experienced a high-temperature “bottleneck” which forced them to simplify the cell structure and get rid of most of RNA structures. As a result, most RNAs in contemporary bacteria and archaea are short and short-lived.
It is not surprising that a satisfactory explanation of the emergence of cellular organization is, in the absence of any paleontological clues, almost impossible. Was the enclosure into a membrane-bounded compartment a necessary precondition or a late event? There is no problem with envisaging the existence of abiotically conceived membranes of a sort. This would help to establish early respiration and photosynthesis. However, many authors view as insurmountable the problem of communication of the enclosed “cytoplasm” with the environment, in the absence of specific transducers. If, however, metabolism began in a homogeneous “soup” or as a 2-dimensional “pizza”, how did it become enclosed later? Which came first – metabolism or replication - and how did the whole become coordinated? The survey of existing theories of cell origin shows that many of them assume a linear (one-by-one accumulation) and gradual (small, infinitesimal steps of accumulation of changes) scenarios. But the first cells may also have come into existence as a happy synchronous merger of many parallel processes that had been going on for hundreds of millions of years. Such singularities are characteristic of the development of complex dissipative systems (this is why their history and future development cannot, in principle, be revealed or predicted in full detail). The prebiotic brew (whatever it was) must have been ripe with such events coming and going. Once the cells came into existence, they quickly mastered the environment available, and erased the vestiges of previous evolution.
The emergence of cellular life is often considered as a milestone. From this point on, the “inorganic” forces molding the planet had a rival which began the “fertilization” of the planet’s surface layers according to its own rules. But does such a metaphor give a realistic view of events? The Earth (like any other planet) had existed from the very outset as a huge dissipative structure feeding on energy of internal origin, as well as that coming from the Sun. Due to initial preconditions (size, distance from the Sun, composition, etc.) and the contingencies along the path, the developmental trajectory has led, in different compartments (water reservoirs, atmosphere, deep layers of the crust), to syntheses of special (inorganic and organic) compounds, to the emergence of complicated structures, and to the establishment of communication between compartments. Each event in such a network fed back and modified the course of future events – evolution was cumulative even at this stage. In this way, the whole planet was “organic”, but at this level of affairs it was distinguished from other kinds of dissipative structures only in its degree of complexity. It had no memory of the past, no other store of information than the structures themselves. The crucial step, then, was indeed the invention of information storage in the form of a replicable code consisting of digital characters. Both replicators and dissipative structures may have existed in parallel for eons. The real emergence of life occurred when some attributes of the dissipative structures acquired the ability to be stored in a form which itself is not a dissipative structure, and then to bring these attributes again into life by a process of decoding. When, where and how this relation became established is the real enigma of life’s origin. After this, the whole subsequent evolution of the Planet is determined also by natural selection of self-replicating entities.
The emergence of cells may have been just an episode in the ongoing planetary process, inconspicuous at that time. Compartmentalization of life into cells highly increased the efficiency of both metabolism and heredity. But even contemporary cells – bacteria and archea - are very strange “individuals” from our point of view. They are genetically and metabolically interconnected over the entire planet, they actually live everywhere – from very deep layers of the crust (down to 10 km) up to the most extraordinary biotopes on the surface - and they may participate in almost any kind of geological processes (see Earth as an Abode of Life). Biology recognizes the appearance of “bacterial” cells some 3.8 Ga ago. Surprisingly, it has very little to say about the subsequent period of 3 Ga – from the biologist’s point of view, in fact, “nothing happened”, and real evolutionary research is usually only interested in events from the late Precambrium onwards. At this time true individuals – sexual multicellular eukaryotes – emerged. These are the only organisms that almost completely cut themselves off from the planetary genetic continuum, and this enabled them to enter the realm of clonal multicellular forms of life. The price they pay for this achievement is their mortality.
The preceding period, however, was the age when the “planetary organism” may have displayed a single form of life. Bacteria and archea (and, very probably, many other now extinct forms of life) took over the evolution of the planetary surface. They became the leading force in molding it into its present state: the appearance of oxygen in the atmosphere is the most notable example of such an activity, yet it represents but a tiny fraction of all the work done. Extrapolations of evolutionary theories, developed for multicellular eukaryotes, to the realm of bacteria and archaea may not be convincing, because the planetary dimension of these forms of life tends to be neglected.
The work of the author was, in part, supported by the Charles University grant No. 117/1998.
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