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Eörs Szathmáry

Publications and source records attributed to Eörs Szathmáry.

18 recordsLinked to original sources

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.

Biological Evolution↗

Selective scenarios for the emergence of natural language.

The recent blossoming of evolutionary linguistics has resulted in a variety of theories that attempt to provide a selective scenario for the evolution of early language. However, their overabundance makes many researchers sceptical of such theorising. Here, we suggest that a more rigorous approach is needed towards their construction although, despite justified scepticism, there is no agreement as to the criteria that should be used to determine the validity of the various competing theories. We attempt to fill this gap by providing criteria upon which the various historical narratives can be judged. Although individually none of these criteria are highly constraining, taken together they could provide a useful evolutionary framework for thinking about the evolution of human language.

Biological Evolution↗

In vitro selection of halo-thermophilic RNA reveals two families of resistant RNA.

The "RNA world" hypothesis proposes that early in the evolution of life, RNA was responsible both for the storage and transfer of genetic information and for the catalysis of biochemical reactions. One of the problems of the hypothesis is that RNA is known to be temperature sensitive. Nevertheless, different types of sequences with a thermostable phenotype may exist. In order to test this possibility, we applied an in vitro evolution method (SELEX) to isolate RNA molecules that are resistant at high temperatures (80 degrees C for 65 h) and high salt concentrations (2 M NaCl). The sequences of the resulting cloned halo-thermophilic RNAs can be grouped in two families (I and II) possessing very different thermal and chemical stabilities and very different secondary structures. The selected RNA molecules illustrate two different possibilities leading to thermal resistance which may be related to primitive conditions. We propose that members of family I constitute a good means of storing sequence information while members of family II are less efficient but replicate faster in early steps of the SELEX. These selected RNA behaviors may be related to primitive conditions and could allow to define limits for survival, and demonstrate that what is at stake for RNA molecules, as for living organisms, is survival and reproduction.

Base Sequence↗

The Budapest Meeting 2005 intensified networking on ethics of science: the case of reproductive cloning, germline gene therapy and human dignity.

This paper reports on the meeting of the Sounding Board of the EU Reprogenetics Project that was held in Budapest, Hungary, 6-9 November 2005. The Reprogenetics Project runs from 2004 until 2007 and has a brief to study the ethical aspects of human reproductive cloning and germline gene therapy. Discussions during The Budapest Meeting are reported in depth in this paper as well as the initiatives to involve the participating groups and others in ongoing collaborations with the goal of forming an integrated network of European resources in the fields of ethics of science.

Cloning, Organism↗

Coexistence and error propagation in pre-biotic vesicle models: a group selection approach.

Compartmentalization of unlinked, competing templates is widely accepted as a necessary step towards the evolution of complex organisms. However, preservation of information by templates confined to isolated vesicles of finite size faces much harder obstacles than by free templates: random drift allied to mutation pressure wipe out any template that does not replicate perfectly, no matter how small the error probability might be. In addition, drift alone hinders the coexistence of distinct templates in a same compartment. Here, we investigate the conditions for group selection to prevail over drift and mutation and hence to guarantee the maintenance and coexistence of distinct templates in a vesicle. Group selection is implemented through a vesicle survival probability that depends on the template composition. By considering the limit case of an infinite number of vesicles, each one carrying a finite number of templates, we were able to derive a set of recursion equations for the frequencies of vesicles with different template compositions. Numerical iteration of these recursions allows the exact characterization of the steady state of the vesicle population-a quasispecies of vesicles-thus revealing the values of the mutation and group selection intensities for which template coexistence is possible. Within the main assumption of the model-a fixed, finite or infinite, number of vesicles-we find no fundamental impediment to the coexistence of an arbitrary number of template types with the same replication rate inside a vesicle, except of course for the vesicle capacity. Group selection in the form of vesicle selection is a must for compartmentalized primordial genetic systems even in the absence of intra-genomic competition of different templates.

Animals↗

Real ribozymes suggest a relaxed error threshold.

The error threshold for replication, the critical copying fidelity below which the fittest genotype deterministically disappears, limits the length of the genome that can be maintained by selection. Primordial replication must have been error-prone, and so early replicators are thought to have been necessarily short. The error threshold also depends on the fitness landscape. In an RNA world, many neutral and compensatory mutations can raise the threshold, below which the functional phenotype, rather than a particular sequence, is still present. Here we show, on the basis of comparative analysis of two extensively mutagenized ribozymes, that with a copying fidelity of 0.999 per digit per replication the phenotypic error threshold rises well above 7,000 nucleotides, which permits the selective maintenance of a functionally rich riboorganism with a genome of more than 100 different genes, the size of a tRNA. This requires an order of magnitude of improvement in the accuracy of in vitro-generated polymerase ribozymes. Incidentally, this genome size coincides with that estimated for a minimal cell achieved by top-down analysis, omitting the genes dealing with translation.

Base Pairing↗

Recombination in primeval genomes: a step forward but still a long leap from maintaining a sizable genome.

A stubborn question in early molecular evolution is how to sustain the "minimum" informational length required for the basic features of life with a putative low-copying fidelity RNA polymerase ribozyme. Proposals to circumvent the information crisis have primarily focused on networks of cooperative molecules or compartmentalization of non-cooperative unlinked templates, but success has been very limited so far. Lehman (2003) has recently suggested that recombination--a frequently ignored player in early evolution--could have been crucial to building up primeval genomes of sizable length. Here we investigate this claim by assuming (without loss of generality) that genes were already enclosed in a compartment (vesicle, protocell). The numerical results show a quite intricate interplay among mutation, recombination, and gene redundancy. Provided that the minimum number of gene copies per protocell was enough for recombination to recreate wildtype templates--but not too high to impose an unbearable burden of mutants--informational content could have increased by at least 25% by keeping the same mutational load as that for a population without recombination. However, the upper bound of informational length would still be far from the "minimal life" provisions.

Chromosome Positioning↗

Dark Dune Spots: possible biomarkers on Mars?

Dark Dune Spots (DDSs) are transitional geomorphologic formations in the frost-covered polar regions of Mars. Our analysis of the transformations and arrangements of subsequent stages of DDSs into time sequence revealed their: (i) hole-like characteristics, (ii) development and formation from the bottom of the frosted layer till the disapperance of the latter, (iii) repeated (seasonal and annual) appearance in a pattern of multiple DDSs on the surface, and (iv) probable origin. We focused our studies on a model in which DDSs were interpreted as objects triggered by biological activity involved in the frosting and melting processes. We discuss two competing interpretations of DDSs: development by defrosting alone, and by defrosting and melting enhanced by the activity of Martian Surface Organisms (MSOs). MSOs are hypothetical Martian photosynthetic surface organisms thought to absorb sunlight. As a result they warm up by late winter and melt the ice around them, whereby their growth and reproduction become possible. The ice cover above the liquid water lens harbouring the MSOs provides excellent heat and UV insulation, prevents fast evaporation, and sustains basic living conditions until the ice cover exists. When the frost cover disappears MSOs go to a dormant, desiccated state. We propose further studies to be carried out by orbiters and landers travelling to Mars and by analysis of partial analogues on earth.

Cold Climate↗

Origin of sex revisited.

Why did sex ever arise in the first place? Why it does not disappear in view of the greater efficiency of asexuals? These are clearly two different questions, and we suggest here that the solution for the origin of sex does not necessarily come from theoretical considerations based on currently existing genetic systems. Thus, while we agree with a number of authors in that the emergence of sex (understood as the exchange of genetic material between genomes) is deeply rooted in the origin of life and happened during the very early stages in the transition from individual genes ('replicators') to bacteria-like cells ('reproducers'), we challenge the idea that recombinational repair was the major selective force for the emergence of sex. Taking the stochastic corrector model as a starting point, we provide arguments that question the putative costs of redundancy in primitive protocells. In addition, if genes that cause intragenomic conflict (i.e., parasites) are taken into account, it is certainly wrong to suggest that cellular fusion would be beneficial at the population level (although this strong claim needs some qualifications). However, when a continuous input of deleterious mutations that impair the fitness of the protocell as a whole is considered in the model (in the realistic range in which stable mutant distributions of quasi-species within compartments are established), there are circumstances when sex could be beneficial as a side effect of the dynamic equilibrium between cellular fusion-mutation-selection. The scenario we have explored numerically is fully consistent with the idea that the universal ancestor was not a discrete entity but an ensemble of proto-organisms that exchanged much genetic information.

Biological Evolution↗

Why are there four letters in the genetic alphabet?

We list, without thinking, the four base types that make up DNA as adenine, guanine, cytosine and thymine. But why are there four? This question is now all the more relevant as organic chemists have synthesized new base pairs that can be incorporated into nucleic acids. Here, I argue that there are theoretical, experimental and computational reasons to believe that having four base types is a frozen relic from the RNA world, when RNA was genetic as well as enzymatic material.

Base Pairing↗

In silico simulations reveal that replicators with limited dispersal evolve towards higher efficiency and fidelity.

The emergence of functional replicases, acting quickly and with high accuracy, was crucial to the origin of life. Although where the first RNA molecules came from is still unknown, it is nevertheless assumed that catalytic RNA enzymes (ribozymes) with replicase function emerged at some early stage of evolution. The fidelity of copying is especially important because the mutation load limits the length of replicating templates that can be maintained by natural selection. An increase in template length is disadvantageous for a fixed digit copying fidelity, however, longer molecules are expected to be better replicases. An iteration for longer molecules with better replicase function has been suggested and analysed mathematically. Here we show that more efficient replicases can spread, provided they are adsorbed to a prebiotic mineral surface. A cellular automaton simulation reveals that copying fidelity, replicase speed and template efficiency all increase with evolution, despite the presence of molecular parasites, essentially because of reciprocal atruism ('within-species mutualism') on the surface, thus making a gradual improvement of replicase function more plausible.

Adsorption↗