Error catastrophe, replication

A hypercycle is a more complex organisation form. Its precondition is the presence of several RNA quasi-species which are able to amalgamate chemically with certain proteins (enzymes or their precursors). If such a protein is linked to a quasi-species, the resulting duo favours the replication of a second quasispecies. According to Dyson, the linked populations get stuck in a stable equilibrium. Problems occur at this level Any theory on the origin of replication has the central problem that the replication process must occur perfectly in order to ensure survival . If there are replication errors, these will increase from generation to generation, until the system collapses the error catastrophe has then occurred ... 

The environmental conditions of the primitive Earth were surely different from those of Spiegelman s and Eigen s test-tubes, but this can be regarded as a secondary complication, and in a first approximation it can be ignored. What we cannot ignore, however, is the fact that any replication process is inevitably affected by errors, and it is therefore imperative to understand the consequences that such errors have for the very survival of a replicating system. This is a crucial problem for all replication-first theories, because it has been proved that any self-replicating system can tolerate replication errors only below a critical threshold. Above such a threshold, the system is overwhelmed by a runaway error catastrophe, and is inexorably condemned to collapse. This is a fundamental problem, and in order to address it we need first to quantify the critical threshold. 

This conclusion allows us to explain the experimental results obtained by Spiegelman and Eigen the RNA molecules of an in vitro replicating system can reach a length of 100-200 monomers, and no more, because longer molecules are overrun by the error catastrophe. The threat of this catastrophe of course also existed for primitive RNAs, whatever the environmental conditions, and we must therefore find out whether it was possible to avoid it. Eigen himself (1977) raised the problem and proposed a possible solution. 

Biological replication, despite its theoretical simplicity, was extremely difficult to achieve in practice, and became possible only with the evolution of a system that was sufficiently complex to withstand the error catastrophes. And the first system that did achieve that complexity level can rightly be regarded as the first living cell. 

Let us now come to the second part of postchemical evolution, the stage that was destined to lead to the origin of the first cells. It is in this stage that we must look for an answer to the problem that the replication paradigm has been unable to solve how did primitive systems manage to increase their complexity without being destroyed by error catastrophes The ribotype answer is based on three points. 

This then is the solution of the ribotype theory in order to avoid the error catastrophes in the journey toward exact replication, it was necessary to have high molecular weight protoribosomes, and the production of these ribosomes for an indefinite number of generations was possible, before exact replication, because ribosoids could achieve it with processes of self-assembly and quasi-replication. The development of high-molecular-weight protoribosomes took place during postchemical evolution, simply because all necessary conditions existed in that period, and the development could be realised with processes that were both natural and primitive. 

Here, ln(ot) is typically 0( 1), while the error rate in the replication of monomer is estimated to be around 0.01-0.1, in the usual polymer replication process. Then the above condition gives N < 100 or so. In other words, information using a polymer with a sequence longer than this threshold N is hardly sustained. This problem was first posed by Eigen and is called error catastrophe [7]. On the other hand, information for the replication for a minimal life system must require much more information. Of course, the error rate could be reduced once some machinery for faithful replication as in the present life emerges. However, such machinery requires much more information to be transmitted by the polymer. 

One might say that the maintenance of replication is not surprising at all, since a gene for the DNA polymerase is included in the beginning. However, enzyme with such catalytic activity is rare. Indeed, with mutations some proteins that lost such catalytic activity but are synthesized in the present system could appear, which might take over the system. Then the self-replication activity would be lost. In fact, this is nothing but the error catastrophe by Eigen, discussed in Section n.A. Then, why is the self-replication activity maintained in the present experiment ... 

We have recently developed a quasi-species approach for analyzing mutation and selection in catalytic reactions of varying order. We discussed how the error catastrophe that reflects the transition from localized to delocalized quasi-species population is affected by catalytic replication of different reaction orders. Specifically, the second-order mechanisms lead to a discontinuity in the mean fimess of the popnlation at the error threshold. This is in contrast to the behavior of the first-order, antocatalytic replication mechanism, considered in the standard quasi-species model. This suggested that quasi-species models with higher order of replication mechanisms produce discontinuities in the mean fitness and, hence, in the viable population fraction, at the error threshold, while lower-order replication mechanisms yield a continuous mean fitness fnnction. 

Low copying fidelities can lead to an error catastrophe where a replicative process cannot maintain the sequence information [41—45]. The error threshold marks the onset of this catastrophe it refers to a critical value in the ratio n s of the mutation rate to the selection strength s. Beyond the threshold, the mutants with compromised function dominate over the original master sequence, because the... 

It is important to note, however, that the concept of an error threshold can acquire a somewhat different meaning in the prebiotic context. In particular, if we consider the molecules that form the core of a primitive replication process, then the most fundamental maintenance requirement is that the process generates at least one functional copy per core replication molecule before the template is destroyed. This situation differs from the standard error threshold scenario In the latter case, both master and mutants replicate and an error catastrophe results from their competition, whereas in the former case the catastrophe is no replication at all. However, this replication breakdown can also be induced by a low copying fidelity. 

Protein synthesis is a series of reactions, each with a high degree of fidelity. Yet mistakes can occur as a result of mistranslation, incorporation of unusual amino acids that are substrates of tRNA acylation reactions, premature termination of nascent peptides, and point mutations where amino acids are substituted (Ballard, 1977). Errors in protein synthesis are especially important if they are introduced into an enzyme, since the catalytic properties of the enzyme may be modified. If such errors occurred in ribosomal proteins or in other enzymes associated with protein synthesis, RNA synthesis, or DNA replication, a cell could be faced with a cataclysmic series of mistakes. Indeed, this concept forms the basis of a theory of aging, the "error catastrophe" theory of Orgel (1963, 1973). It is hardly surprising, therefore, that cells... 

For the time being, therefore, the only reasonable conclusion is that a true replication mechanism appeared only at the end of precellular evolution, when the first cells came into being. Both chemical evolution and postchemical evolution, in other words, had to take place with metabolic systems that were able to tolerate errors, because only in this way could they be immune to the replication catastrophes. 

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