Search PubMed⌕ Search

Biomedical subjects

E Szathmáry

Publications and source records attributed to E Szathmáry.

At least 19 recordsLinked to original sources
PubMed2001

Survival of replicators with parabolic growth tendency and exponential decay.

The claim that the competition of parabolically growing self-replicators leads to dynamically stable coexistence was challenged by Lifson & Lifson [(1999). J. theor. Biol.199, 425-433]. They have shown that, if single- and double-strands are treated separately, and only single-strands undergo spontaneous decay, then there is natural selection rather than survival of everybody. We use their models to show that if double-strand decay is not neglected, then dynamical coexistence is still possible under a wide range of parameter values, in agreement with the chromatographized replicator model of von Kiedrowski & Szathmáry [(2000). Selection 1-3, 173-179]. Coexistence is always ensured above a critical resource (monomer) inflow rate. Recycling of decayed replicators into monomers further favours dynamical coexistence. The claim that parabolic growth invariably results in coexistence remains valid for the model for which it was meant to apply, namely for parabolic growth without template decay. Exponential decay acting on single- and double-strands, combined with parabolic growth, may or may not result in a dynamical coexistence of self-replicators.

Animals↗
PubMed2001

Comparable system-level organization of Archaea and Eukaryotes.

A central and long-standing issue in evolutionary theory is the origin of the biological variation upon which natural selection acts. Some hypotheses suggest that evolutionary change represents an adaptation to the surrounding environment within the constraints of an organism's innate characteristics. Elucidation of the origin and evolutionary relationship of species has been complemented by nucleotide sequence and gene content analyses, with profound implications for recognizing life's major domains. Understanding of evolutionary relationships may be further expanded by comparing systemic higher-level organization among species. Here we employ multivariate analyses to evaluate the biochemical reaction pathways characterizing 43 species. Comparison of the information transfer pathways of Archaea and Eukaryotes indicates a close relationship between these domains. In addition, whereas eukaryotic metabolic enzymes are primarily of bacterial origin, the pathway-level organization of archaeal and eukaryotic metabolic networks is more closely related. Our analyses therefore suggest that during the symbiotic evolution of eukaryotes, incorporation of bacterial metabolic enzymes into the proto-archaeal proteome was constrained by the host's pre-existing metabolic architecture.

Archaea↗
PubMed2000

The evolution of replicators.

Replicators of interest in chemistry, biology and culture are briefly surveyed from a conceptual point of view. Systems with limited heredity have only a limited evolutionary potential because the number of available types is too low. Chemical cycles, such as the formose reaction, are holistic replicators since replication is not based on the successive addition of modules. Replicator networks consisting of catalytic molecules (such as reflexively autocatalytic sets of proteins, or reproducing lipid vesicles) are hypothetical ensemble replicators, and their functioning rests on attractors of their dynamics. Ensemble replicators suffer from the paradox of specificity: while their abstract feasibility seems to require a high number of molecular types, the harmful effect of side reactions calls for a small system size. No satisfactory solution to this problem is known. Phenotypic replicators do not pass on their genotypes, only some aspects of the phenotype are transmitted. Phenotypic replicators with limited heredity include genetic membranes, prions and simple memetic systems. Memes in human culture are unlimited hereditary, phenotypic replicators, based on language. The typical path of evolution goes from limited to unlimited heredity, and from attractor-based to modular (digital) replicators.

Carbohydrate Metabolism↗
PubMed1999

The origin of the genetic code: amino acids as cofactors in an RNA world.

The genetic code, understood as the specific assignment of amino acids to nucleotide triplets, might have preceded the existence of translation. Amino acids became utilized as cofactors by ribozymes in a metabolically complex RNA world. Specific charging ribozymes linked amino acids to corresponding RNA handles, which could basepair with different ribozymes, via an anticodon hairpin, and so deliver the cofactor to the ribozyme. Growing of the 'handle' into a presumptive tRNA was possible while function was retained and modified throughout. A stereochemical relation between some amino acids and cognate anticodons/codons is likely to have been important in the earliest assignments. Recent experimental findings, including selection for ribozymes catalyzing peptide-bond formation and those utilizing an amino acid cofactor, hold promise that scenarios of this major transition can be tested.

Amino Acids↗
PubMed1997

From replicators to reproducers: the first major transitions leading to life.

A classification of replicators is proposed: life depends on replicators that can exist in an indefinitely large number of forms (unlimited heredity), and whose replication is modular rather than processive. The first template replicators would have increased at a rate less than exponential, because of self-inhibition arising from molecular complementarity. The result would be the survival of a varied population of replicators, rather than the victory of one type. This variability was important, because inaccurate copying meant that individual replicators were small (Eigen's paradox). The origin of cooperation between replicators, and the problem of molecular parasites, are discussed. Today, cooperation depends on cellular compartments, and on the linkage of genes on chromosomes, but we argue that at an earlier stage surface metabolism, in which replicators react only with neighbours, was important. The origin of translation and the genetic code is discussed. The essential step is the binding of amino acids to specific oligonucleotides. We suggest that this binding originated, not as a step in protein synthesis, but in the formation of coenzymes in a metabolically complex RNA world. Existing organisms are not replicators (that is, new individuals do not arise by copying), but reproducers that contain replicators. We outline Griesemer's concept of a reproducer, which brings out the essential role of development in evolution.

Animals↗
PubMed1995

A classification of replicators and lambda-calculus models of biological organization.

W. Fontana & L.W. Buss (Proc. Natn. Acad. Sci. U.S.A. 91, 757 (1994) and Bull. math. Biol. 56, 1 (1994) have put forward a scheme for a theory of biological organization based on the lambda-calculus. Their key innovation was to represent, with the aid of this calculus, a certain minimal chemistry. Although this idea is very promising, their concrete formulation could be improved if suggestions for the following items were incorporated: (i) a better coding of chemical reactions; (ii) a reinterpretation of the evolutionary behaviour of autocatalytic chemical networks; (iii) a better appreciation of morphological and genetic factors; (iv) a more complete embedding of the theory into the background of relevant earlier contributions. Confusion can be stopped by the application of a proper classification of replicators (important categories being: processive and modular, limited and unlimited hereditary replicators). Suggestions to facilitate improvement are made explicit in this paper. The most challenging task would be to model the transition from processive, limited hereditary replicators to modular replicators with limited and unlimited heredity.

Amoeba↗
PubMed1995

The major evolutionary transitions.

There is no theoretical reason to expect evolutionary lineages to increase in complexity with time, and no empirical evidence that they do so. Nevertheless, eukaryotic cells are more complex than prokaryotic ones, animals and plants are more complex than protists, and so on. This increase in complexity may have been achieved as a result of a series of major evolutionary transitions. These involved changes in the way information is stored and transmitted.

Animals↗
PubMed1994

Toy models for simple forms of multicellularity, soma and germ.

Simple models for the development, maintenance, and origins of primitive, one- or two-dimensional "toy organisms" are presented. They are similar to cellular automata with the added combination of internal degrees of freedom that are genetically programmed. The growing rules are implementable by cellular mechanics, biochemistry and genetics. The forms that are dealt with are: sexual unicells, filaments with fragmentation, cell doublets with spore formation, filaments with differentiation of soma and germ, and two-dimensional colonies with early segregation of somatic cells and germ line. The minimum models presented help to understand the feasibility of several important evolutionary transitions. An explanation, supported by the models, for the fact that all three multicellular kingdoms are primarily sexual, is offered by the observation that sexuality in unicells is an excellent preadaptation for development, for the former entails programmed differentiation of cell types (relying in part on the action of homeobox genes), use of cell surface molecules, programmed arrest of cell division, etc. Relevant examples of existing biological systems are also presented.

Animals↗
PubMed1993

Co-operation and defection: playing the field in virus dynamics.

A previous model (Szathmáry, 1992) is further developed for the dynamics of standard (V) and defective interfering (DI) viruses. The crucial retained element is the incorporation of population structure in the form of a complete distribution of cells infected by particles differing in number. New elements are: the non-linear shared benefit from the contribution of Vs to the group of viruses infecting the same cell (synergistic at low numbers, diminishing returns at high numbers, respectively); a dynamics for the total number of particles (V and DI); and the possibility of extinction if the frequency of Vs is small enough. In evolutionary genetical terms this is a frequency- and density-dependent evolutionary game. A crucial result is retained: coexistence of Vs and DIs is possible provided the multiplicity of infection (hence the size of the coinfection group) is large enough. Phase portraits and vector-field plots for a continuous-time and numerical solutions for a corresponding discrete-time case are presented. The latter reflect the basic features of serial, undiluted passage. The causes for two possible means of extinction (low initial frequency of Vs, and very high vigour of Vs) are revealed: the appearance of high amplitude fluctuations. Coexistence can apparently be ensured by stable points, periodic behaviour, or strange attractors. The paper clarifies the dynamical background of cycles found experimentally in V-DI systems.

Biological Evolution↗
PubMed1993

Coding coenzyme handles: a hypothesis for the origin of the genetic code.

The coding coenzyme handle hypothesis suggests that useful coding preceded translation. Early adapters, the ancestors of present-day anticodons, were charged with amino acids acting as coenzymes of ribozymes in a metabolically complex RNA world. The ancestral aminoacyl-adapter synthetases could have been similar to present-day self-splicing tRNA introns. A codon-anticodon-discriminator base complex embedded in these synthetases could have played an important role in amino acid recognition. Extension of the genetic code proceeded through the take-over of nonsense codons by novel amino acids, related to already coded ones either through precursor-product relationship or physicochemical similarity. The hypothesis is open for experimental tests.

Amino Acyl-tRNA Synthetases↗
PubMed1993

The origin of chromosomes. I. Selection for linkage.

A model is analysed of cells containing independently replicating genes, which segregate randomly when the cell divides. We follow the fate of a primitive chromosome, in which two genes are linked, so that they replicate and segregate together. Such a chromosome increases in frequency in the population provided that (i) the two genes act synergistically, so that a cell containing at least one copy of each grows faster than a cell lacking one or other, and (ii) the number of genes per cell is small. The increase in frequency occurs even if the chromosome takes twice as long as an individual gene to replicate, giving a two-fold selective disadvantage within a cell. The increase occurs because a gene that is linked does not run the risk of finding itself, in the next generation, in a cell that lacks its synergistic partner.

Animals↗
PubMed1993

The evolution of chromosomes. II. Molecular mechanisms.

It is likely that there was a phase in evolution when the genome consisted of unlinked RNA genes, separately replicated. In this paper, we suggest molecular mechanisms whereby (i) separate RNA genes could have become linked to form chromosomes, (ii) monocistronic transcripts could have been made from these chromosomes, and (iii) RNA was replaced by DNA as the genetic material.

Animals↗