The origin of replicators and reproducers

Replicators are fundamental to the origin of life and evolvability. Their survival depends on the accuracy of replication and the efficiency of growth relative to spontaneous decay. Infrabiological systems are built of two coupled autocatalytic systems, in contrast to minimal living systems that must comprise at least a metabolic subsystem, a hereditary subsystem and a boundary, serving respective functions. Some scenarios prefer to unite all these functions into one primordial system, as illustrated in the lipid world scenario, which is considered as a didactic example in detail. Experimentally produced chemical replicators grow parabolically owing to product inhibition. A selection consequence is survival of everybody. The chromatographized replicator model predicts that such replicators spreading on surfaces can be selected for higher replication rate because double strands are washed away slower than single strands from the surface. Analysis of real ribozymes suggests that the error threshold of replication is less severe by about one order of magnitude than thought previously. Surface-bound dynamics is predicted to play a crucial role also for exponential replicators: unlinked genes belonging to the same genome do not displace each other by competition, and efficient and accurate replicases can spread. The most efficient form of such useful population structure is encapsulation by reproducing vesicles. The stochastic corrector model shows how such a bag of genes can survive, and what the role of chromosome formation and intragenic recombination could be. Prebiotic and early evolution cannot be understood without the models of dynamics.     

From survivors to replicators: evolution by natural selection revisited

For evolution by natural selection to occur it is classically admitted that the three ingredients of variation, difference in fitness and heredity are necessary and sufficient. In this paper, I show using simple individual-based models, that evolution by natural selection can occur in populations of entities in which neither heredity nor reproduction are present. Furthermore, I demonstrate by complexifying these models that both reproduction and heredity are predictable Darwinian products (i.e. complex adaptations) of populations initially lacking these two properties but in which new variation is introduced via mutations. Later on, I show that replicators are not necessary for evolution by natural selection, but rather the ultimate product of such processes of adaptation. Finally, I assess the value of these models in three relevant domains for Darwinian evolution.     

Viral sex, levels of selection, and the origin of life.

Several issues in Chao's related paper J. theor. Biol. (1991, 153, 229-246) are revisited. It is argued that mixes of segments from different viral coinfection groups cannot be regarded as sex, unless one is willing to accept that these groups are replicators and individuals. But, because selection in coinfection groups is dynamically analogous to that in trait groups in structured demes, one should also regard these latter groups as replicators. This approach is unacceptable since the groups in question have irregular ploidies, an unfixed number of parents, and no rules analogous to those of meiosis. It is emphasized, however, that the effective presence of neighbour-modulated fitness can ensure dynamical coexistence of covirus segments, even if the equal net reproduction rate within groups is not warranted. It seems that during the origin of coviruses from complete viruses, a higher-level evolutionary unit has become disintegrated, whereas during the origin of life a higher-level unit, the protocell, has emerged from lower-level ones, i.e. unlinked, replicating genes. These two gene-level systems are not homologous, but analogous. Although it is true that the resistance to parasites and the need to avoid a mutational collapse of the genome are likely to have called for some compartmentation in precellular stages of evolution, no clear demonstration, that the proposed mechanisms (the compartmentalized hypercycle and the stochastic corrector model) do in fact solve the error threshold problem, exists. Neither has a plausible mode of protocellular sex been suggested.     

G4 motifs affect origin positioning and efficiency in two vertebrate replicators

DNA replication ensures the accurate duplication of the genome at each cell cycle. It begins at specific sites called replication origins. Genome‐wide studies in vertebrates have recently identified a consensus G‐rich motif potentially able to form G‐quadruplexes (G4) in most replication origins. However, there is no experimental evidence to demonstrate that G4 are actually required for replication initiation. We show here, with two model origins, that G4 motifs are required for replication initiation. Two G4 motifs cooperate in one of our model origins. The other contains only one critical G4, and its orientation determines the precise position of the replication start site. Point mutations affecting the stability of this G4 in vitro also impair origin function. Finally, this G4 is not sufficient for origin activity and must cooperate with a 200‐bp cis‐regulatory element. In conclusion, our study strongly supports the predicted essential role of G4 in replication initiation.     

Lethal mutants and truncated selection together solve a paradox of the origin of life

Background

Many attempts have been made to describe the origin of life, one of which is Eigen''s cycle of autocatalytic reactions [Eigen M (1971) Naturwissenschaften 58, 465–523], in which primordial life molecules are replicated with limited accuracy through autocatalytic reactions. For successful evolution, the information carrier (either RNA or DNA or their precursor) must be transmitted to the next generation with a minimal number of misprints. In Eigen''s theory, the maximum chain length that could be maintained is restricted to nucleotides, while for the most primitive genome the length is around . This is the famous error catastrophe paradox. How to solve this puzzle is an interesting and important problem in the theory of the origin of life.

Methodology/Principal Findings

We use methods of statistical physics to solve this paradox by carefully analyzing the implications of neutral and lethal mutants, and truncated selection (i.e., when fitness is zero after a certain Hamming distance from the master sequence) for the critical chain length. While neutral mutants play an important role in evolution, they do not provide a solution to the paradox. We have found that lethal mutants and truncated selection together can solve the error catastrophe paradox. There is a principal difference between prebiotic molecule self-replication and proto-cell self-replication stages in the origin of life.

Conclusions/Significance

We have applied methods of statistical physics to make an important breakthrough in the molecular theory of the origin of life. Our results will inspire further studies on the molecular theory of the origin of life and biological evolution.     

Selection without replicators: the origin of genes, and the replicator/interactor distinction in etiobiology

Genes are thought to have evolved from long-lived and multiply-interactive molecules in the early stages of the origins of life. However, at that stage there were no replicators, and the distinction between interactors and replicators did not yet apply. Nevertheless, the process of evolution that proceeded from initial autocatalytic hypercycles to full organisms was a Darwinian process of selection of favourable variants. We distinguish therefore between Neo-Darwinian evolution and the related Weismannian and Central Dogma divisions, on the one hand, and the more generic category of Darwinian evolution on the other. We argue that Hull’s and Dawkins’ replicator/interactor distinction of entities is a sufficient, but not necessary, condition for Darwinian evolution to take place. We conceive the origin of genes as a separation between different types of molecules in a thermodynamic state space, and employ a notion of reproducers.     

Prelife catalysts and replicators

Life is based on replication and evolution. But replication cannot be taken for granted. We must ask what there was prior to replication and evolution. How does evolution begin? We have proposed prelife as a generative system that produces information and diversity in the absence of replication. We model prelife as a binary soup of active monomers that form random polymers. ‘Prevolutionary’ dynamics can have mutation and selection prior to replication. Some sequences might have catalytic activity, thereby enhancing the rates of certain prelife reactions. We study the selection criteria for these prelife catalysts. Their catalytic efficiency must be above certain critical values. We find a maintenance threshold and an initiation threshold. The former is a linear function of sequence length, and the latter is an exponential function of sequence length. Therefore, it is extremely hard to select for prelife catalysts that have long sequences. We compare prelife catalysis with a simple model for replication. Assuming fast template-based elongation reactions, we can show that replicators have selection thresholds that are independent of their sequence length. Our calculation demonstrates the efficiency of replication and provides an explanation of why replication was selected over other forms of prelife catalysis.     

Chance and the origin of life

Random chemical reactions in the Earth's primitive hydrosphere could have generated no more than 200 bits of information, whereas the first Darwinian organism must have encoded about a million bits, and therefore could not have arisen by chance. This information gap is bridged by separating reproduction from organism, and postulating a reproductive chemical community that would generate information by proto-Darwinian evolution. The information content of the initial community could have been as low as 160 bits, and its evolution might have led to the first Darwinian cell.     

Symbiosis and the origin of life

The paper uses chemical kinetic arguments and illustrations by computer modelling to discuss the origin and evolution of life. Complex self-reproducing chemical systems cannot arise spontaneously, whereas simple auto-catalytic systems can, especially in an irradiated aqueous medium. Self-reproducing chemical particles of any complexity, in an appropriate environment, have a self-regulating property which permits long-term survival. However, loss of materials from the environment can lead to continuing decay which is circumvented by physical union between different kinds of self-reproducing particles. The increasing complexity produced by such unions (symbioses) is irreversible so that the chemical system evolves. It is suggested that evolution by successive symbioses brough about the change from simple, spontaneously arising, auto-catalytic particles to complex prokaryotic cells.     

Macromolecules and the origin of life

From our knonwledge of present day organisms, it is hard to imagine a living assembly, even at its most primitive stage, without macromolecules.In order to look for the macromolecules which possibly participated in the assembly of the primitive organisms, the reaction and formation of polymers in HCN under irradiation of ultraviolet ray of 184.9 nm. was studied.As a example of a simple way of producing an assembly of macromolecules, the mechanism of coacervation was studied by using gelatin as the material.     

Chance and the origin of life

Random chemical reactions in the Earth's primitive hydrosphere could have generated no more than 200 bits of information, whereas the first Darwinian organism must have encoded about a million bits, and therefore could not have arisen by chance. This information gap is bridged by separating reproduction from organism, and postulating a reproductive chemical community that would generate information by proto-Darwinian evolution. The information content of the initial comunity could have been as low as 160 bits, and its evolution might have led to the first Darwinian cell.     

Clay and the origin of life

Research concerning the possible role of clay in chemical evolution is reviewed. The probable importance of clays in the origin of life is assessed.     

Geographical distribution and the origin of life: The development of early nineteenth-century British explanations

Conclusions By the 1840s and 1850s biogeographical theory had polarized into two opposing views — both of which had their origins in the sixteenth or seventeenth centuries. At issue in this polarization was the question of God's involvement with His creation. At one end of the spectrum were Sclater, Agassiz, Kirby, and others who saw a neatly designed world in which geographical distributions were planned and executed by the hand of God at creation. For most of these naturalists, organisms were created en masse within the regions they now occupy. Disjunct distributions were proof to them that God had indeed created species in situ as many individuals. These naturalists hoped to reveal God's biogeographical plan by discovering His regions of creation. They had hoped to demonstrate a neatly devised set of regions of creation which might be applicable to all creatures, but in attempting to do so, they arrived at conflicting sets of delineations — thus helping to undermine their conceptions of nature in which design (both idealist and utilitarian) played an important part.⁹³ At the other end of the biogeographical spectrum were the theoretical ideas of Prichard and Lyell, who viewed a more remote God — one who allowed His creation to be shaped and modified by secondary laws. Lyell in particular wished to leave considerations of design aside, hoping to demonstrate that the shape of the present creation is due to natural laws. Prichard and Lyell saw God's role in the creation of species (and distributions) as being extremely limited. In fact, the regions of creation seen today are in actuality only natural artifacts produced by migrations and barriers. They saw distributions being in constant flux, as was the rest of nature.Those supporting the views of Prichard and Lyell spent a great deal of effort in attempting to remove a major obstacle in their paths — disjunct distributions. If disjunct distributions were indeed the products of separate creative acts, as Sclater and others claimed, then the arguments of Prichard and Lyell would be negated. For if the creation of a species was shown to be the product of multiple creations, then what was the need of migrations and dispersal mechanisms? Also at stake, of course, was the concept of species based upon generation. Darwin was well aware that if the supernatural implications of disjunct distributions could not be refuted, then his evolutionary system — founded upon a species concept based on descent — would be in peril.⁹⁴ A further barrier to the acceptance of the Prichard/Lyell view was the fact that those sympathetic to a nonsupernatural explanation of disjunct distributions could not agree upon a natural explanation for those anomalies, and an internal debate between naturalists within this group raged for decades.⁹⁵ By 1859 a biogeographical stalemate had occurred. Sclater and others, supporting their static view of nature, continued to look for regions of creation, pointing to disjunct distributions in support of their arguments, while those favorable to the views of Prichard and Lyell continued to search for natural explanations for such biogeographical anomalies.The key needed to resolve the biogeographical debate was a credible theory for species origins. By 1858 there were essentially three options for British naturalists: supernatural creation, Lamarckian transmutation, or natural creation. A few British naturalists grasped at these straws, but most workers preferred the option of remaining silent until a more viable explanation for the origin and distribution of species could be advanced.⁹⁶ And not until the publication of Darwin's theory did that explanation become available.