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PubMed1990

[Extension of life: the apotheosis of the molecular biomedical sciences?].

Evolutionary biologists have shown that many of the adverse effects associated with the ageing process are the (by)products of certain genes: the manifestation of the negative effects of these genes only late in life has effectively constrained their elimination from the germ line by natural selection. In addition, during evolution genes have evolved that govern mechanisms for the protection of the body against exogenous and endogenous insults. These two types of genes, in interaction both with themselves and with the environment specify the maximum life span of a species. New scientific developments, especially in molecular biology, allow the careful analysis of the genetic information and its manipulation. On the basis of these developments more insight will be obtained in the causes of ageing and it will be possible to design new therapies for many of the adverse effects associated with ageing. In the long term it may be possible to remove the basic causes of ageing by genetic manipulation. The mission of the biomedical sciences may then be considered as completed.

Aged↗
PubMedDate not supplied

Why 4(3) codons?

An attempt is made to answer the question posed by the title of this paper. First we show that in primitive self-replicating oligoribotide systems, selection depended from the very start on the existence of 4 kinds of ribotides, forming 2 complementary pairs. Further selection required that the condensation reactions involving the two last positions of the 3'-end of a growing oligoribotide fragment and the first position of the 5'-end of another fragment were catalyzed by randomly synthesized peptides. This established a codon--amino acid concentration correlation and clinched triplet segments as the basis of the translation process. Finally, physical arguments are given to show that the monochirality of the ribotides arose from stereochemical reasons, as firstly described by Wald, but that of the amino acids is the result of natural selection acting during the peptide-assisted stage of oligoribotide growth.

Amino Acids↗
PubMed2002

Evolution of eukaryotic translation elongation and termination factors: variations of evolutionary rate and genetic code deviations.

Translation is carried out by the ribosome and several associated protein factors through three consecutive steps: initiation, elongation, and termination. Termination remains the least understood of them, partly because of the nonuniversality of the factors involved. To get some insights on the evolution of eukaryotic translation termination, we have compared the phylogeny of the release factors eRF1 and eRF3 to that of the elongation factors EF-1alpha and EF-2, with special focus on ciliates. Our results show that these four translation proteins have experienced different modes of evolution. This is especially evident for the EF-1alpha, EF-2, and eRF1 ciliate sequences. Ciliates appear as monophyletic in the EF-2 phylogenetic tree but not in the EF-1alpha and eRF1 phylogenetic trees. This seems to be mainly because of phylogeny reconstruction artifacts (the long-branch attraction) produced by the acceleration of evolutionary rate of ciliate EF-1alpha and eRF1 sequences. Interaction with the highly divergent actin found in ciliates, or on the contrary, loss of interaction, could explain the acceleration of the evolutionary rate of the EF-1alpha sequences. In the case of ciliate eRF1 sequences, their unusually high evolutionary rate may be related to the deviations in the genetic code usage found in diverse ciliates. These deviations involve a relaxation (or even abolition) of the recognition of one or two stop codons by eRF1. To achieve this, structural changes in eRF1 are needed, and this may affect its evolutionary rate. Eukaryotic translation seems to have followed a mosaic evolution, with its different elements governed by different selective pressures. However, a correlation analysis shows that, beneath the disagreement shown by the different translation proteins, their concerted evolution can still be made apparent when they are compared with other proteins that are not involved in translation.

Animals↗
PubMed1998

Genetic code origins: tRNAs older than their synthetases?

We present a phylogenetic analysis to determine whether a given tRNA molecule was established in evolution before its cognate aminoacyl-tRNA synthetase. The earlier appearance of tRNA versus their metabolically related enzymes is a prediction of the RNA world theory, but the available synthetase and tRNA sequences previously had not allowed a formal comparison of their relative time of appearance. Using data recently obtained from the emerging genome projects, our analysis points to the extant forms of lysyl-tRNA synthetase being preceded in evolution by the establishment of the identity of lysine tRNA.

Amino Acyl-tRNA Synthetases↗
PubMed2004

A stochastic gene evolution model with time dependent mutations.

We develop here a new class of gene evolution models in which the nucleotide mutations are time dependent. These models allow to study nonlinear gene evolution by accelerating or decelerating the mutation rates at different evolutionary times. They generalize the previous ones which are based on constant mutation rates. The stochastic model developed in this class determines at some time t the occurrence probabilities of trinucleotides mutating according to 3 time dependent substitution parameters associated with the 3 trinucleotide sites. Therefore, it allows to simulate the evolution of the circular code recently observed in genes. By varying the class of function for the substitution parameters, 1 among 12 models retrieves after mutation the statistical properties of the observed circular code in the 3 frames of actual genes. In this model, the mutation rate in the 3rd trinucleotide site increases during gene evolution while the mutation rates in the 1st and 2nd sites decrease. This property agrees with the actual degeneracy of the genetic code. This approach can easily be generalized to study evolution of motifs of various lengths, e.g., dicodons, etc., with time dependent mutations.

Codon↗
PubMed1976

A cybernetic approach to the origin of the genetic coding mechanism. I. Methodological principles.

It is postulated that some quasi-deterministic code features (universality, connectedness, systematic degeneracy, symmetry, regularity and so on) resulted from unique (and therefore universal) relization of a stochastic evolutionary process. The evolution of real genetic systems should satisfy the principle of succession; that is, loss of a feature that is necessary for a genetic system means death to its carrier. The hypothesis of unique key coincidence is proposed which indicates the mechanisms of arising of the primary correspondence between the linear structures of polynucleotides and polypeptides. If the collinear coincidence was to appear in the key positions of pra-protein with, at least, some of the primitive properties of the pra-amino-acyl-t-RNA-synthetase required for the accelerated recognition of the key positions of pra-template, the positive feed-back mechanism in the system would be most short-circuited so that the repetitive reproduction of pra-synthetase would be much accelerated.

Amino Acyl-tRNA Synthetases↗
PubMed1999

The genetic code: what is it good for? An analysis of the effects of selection pressures on genetic codes.

How did the "universal" genetic code arise? Several hypotheses have been put forward, and the code has been analyzed extensively by authors looking for clues to selection pressures that might have acted during its evolution. But this approach has been ineffective. Although an impressive number of properties has been attributed to the universal code, it has been impossible to determine whether selection on any of these properties was important in the code's evolution or whether the observed properties arose as a consequence of selection on some other characteristic. Therefore we turned the question around and asked, what would a genetic code look like if it had evolved in response to various different selection pressures? To address this question, we constructed a genetic algorithm. We found first that selecting on a particular measure yields codes that are similar to each other. Second, we found that the universal code is far from minimized with respect to the effects of mutations (or translation errors) on the amino acid compositions of proteins. Finally, we found that the codes that most closely resembled real codes were those generated by selecting on aspects of the code's structure, not those generated by selecting to minimize the effects of amino acid substitutions on proteins. This suggests that the universal genetic code has been selected for a particular structure-a structure that confers an important flexibility on the evolution of genes and proteins-and that the particular assignments of amino acids to codons are secondary.

Algorithms↗
PubMed1988

Temperature adaptation of lactate dehydrogenase. Structural, functional and genetic aspects.

Comparison of the primary structures of thermophilic, mesophilic and psychrophilic lactate dehydrogenase (LDH) reveals a multitude of temperature-related amino acid substitutions. In the substitutions amino acid residues occurring preferentially in thermophilic, mesophilic (psychrophilic) LDH were found. On this basis, amino acid residues could be classified in an order from typical thermophilic (thermostabilizing) to typical mesophilic (thermolabilizing, increasing dynamics of the enzyme molecule) residues. The temperature-dependent ratio between thermostabilizing and thermolabilizing amino acid residues forms the basis for the specific structural and functional properties of thermophilic or mesophilic LDH. It is interesting that there appears to be a relationship between this order from thermophilic to mesophilic amino acid residues and the type of bases coding for these individual residues in the translation step of protein biosynthesis. Temperature-related amino acid substitutions are based on temperature-related base substitutions. A possible mechanism of temperature adaptation of LDH through alternative selection of thermophilic and mesophilic amino acid residues at the level of tRNA (anticodon)-mRNA (codon) interactions is discussed. These temperature-adaptation processes are evolutionary events in which the evolution and structure of the genetic code are involved.

Adaptation, Physiological↗
PubMed1996

On evolutive systems and the initial evolution of structure and function.

As an instrument for the study of the early stages of evolution, we introduce evolutive systems, defined as systems that have the capacity to evolve given appropriate conditions in their environment. They consist of building blocks (e.g. monomers) that are either stable or in steady supply, and of transient assemblies (e.g. polymers) that are entities of great variety, some of which are capable of function. Evolution leads to the accumulation of structure within the transient assemblies during repeated cycles of disintegration (partial or total) and reassembly, on account of the selective advantages associated with transient assembly functions. Transient assemblies must be either inherently unstable or subject to disintegration by agents in their environment. Evolutive systems must have access to a negentropy input in the form of energy in packets larger than typical thermal energies. Reproduction, although not a prerequisite, greatly affects the capacity of evolutive systems to evolve, and thus can be expected to appear in an evolutive system if at all possible. Similarly, functions that require the expenditure of negentropy (for example mobility, breathing, circulation, sensing, communicating, etc.) are not prerequisites for evolution, but can be expected to become established in evolutive systems during evolution through the selective advantages that they confer. A computer-based evolutive automaton is used to explore possible evolutionary scenarios. In the presence of spatial and temporal inhomogeneities, one can construct a multitude of evolutionary scenarios through which various functions, such as the operation of genetic code, can become established within the evolutive automaton. This variety of possible evolutionary scenarios is all the more remarkable because the automaton does not include many important physical processes that would be present in a real system and would greatly multiply the number of possible evolutionary mechanisms and scenarios. Some evolutionary mechanisms are based on survival related selection, while others are based on generation related selection. Previously explored scenarios for the initiation of life have been based mostly on generation related selection. In this paper, we give particular emphasis to survival related selection which is more general in that it does apply to structures and functions related to reproduction but, unlike generation related selection, it is not limited to them. Some of the most basic features of terrestrial living systems can be seen either as prerequisite features of an evolutive system (such as the mortality of living organisms, instability of biological polymers, imperfect reproduction caused by mutations, and the need for a negentropy input) or as features that one can reasonably expect to become established in an evolutive system (such as reproduction and the multitude of living functions that require expenditure of negentropy). This suggests the possibility that an independent definition of living systems may not be necessary if features of living systems substantially overlap with features that one may expect to find in evolutive systems.

Animals↗
PubMed1992

Radionuclide-induced evolution of DNA and the origin of life.

Artesian groundwaters of high radionuclide concentration are ubiquitous and may have provided the large, sustained energy sources that were required to drive the multistage process of DNA and primordial cell evolution. The rapid, early development of the genetic code as well as its degeneracy can be attributed to exceptionally high radiation-induced mutation rates in this unique environment. The ability of double-strand DNA to direct enzymatic repair of radiation damage to single strands contributed importantly to its selective evolution. It is postulated that the polymerization of nucleotides took place at elevated temperatures within alpha-particle tracks of high ion and free-radical density, followed by rapid quenching to ambient conditions. It also is evident that radiation resistance and ploidy were important selection factors in cellular evolution.

Biological Evolution↗
PubMed2005

On the coevolution of genes and genetic code.

The canonical genetic code acts efficiently in minimizing the effects of mistranslations and point mutations. In the work presented we have also considered the effects of single nucleotide insertions and deletions on the optimality of the genetic code. Our results suggest that the canonical genetic code compensates for the ins/del mutations as well as mistranslations and point mutations. On the other hand, we highlighted the point that ins/del mutations have a lesser impact on the selected genes of Saccharomyces cerevisiae compared to randomly generated ones. We hypothesized that the codon usage preferences in S. cerevisiae genes are responsible for the higher efficiency of translation machinery in this organism. Our results support the conjecture that codon usage preferences render the genetic code more effective in minimizing the effects of ins/del mutations.

Animals↗