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PubMedDate not supplied

[Again on language of biology].

Some time ago I proposed in an Editorial in this journal some considerations on the language of biology. I concluded that, to realize an autonomy of such a language (and therefore of biology), we have to develop a valid language for biology. In such a context, it seemed to me that the term "metaphors" referred to the concepts concerning the information carried by genetic code, was a reasonable one. However, Barbieri's article in this issue of Rivista di Biologia / Biology Forum calls for a reply. Of course, we do not know very much in this field, even if we have some evidence that a sequence of bases on a DNA is not determined only by chance. In any case we can exclude that nature in this occasion has "invented" a code. Nature doesn't "invent" anything: it only follows its rules, that we name "laws of nature". Barbieri quotes the Morse code, but forgets to say that such a code is "conventional" in the sense that it is valid only because it is the result of an "agreement" between Morse and the users of that code. There is nothing more unnatural than a "code": with whom nature should actually have to "reach an agreement"? As a matter of fact, we interpret as "information" what happens by law of nature. Also Barbieri's thesis that genes and proteins are molecular artifacts, assembled by external agents, whereas generally molecules are determined by their bonds, i.e. by internal factors, is a disputable one. It is examined how much an external structure plays a role in ordinary chemical reactions. The "information" of physics is not a semantic information. For such information we can refer to history of literature, telegraphic offices, genetics or biochemistry.

Biology↗
PubMed1989

[Role of the code redundancy in determining cotranslational protein folding].

It has been demonstrated earlier in our laboratory that rare codon clusters can determine the boundaries of the polypeptide chain fragments of the same secondary structure type during the co-translational protein folding. According to this data, co-translational protein folding can occur under condition of a correlation between the frequency of codon choice in mRNAs and the relative abundance of their isoaccepting tRNAs. The alterations in the spectrum and concentrations of the isoaccepting tRNAs in different cells were demonstrated by many authors. The existence of a mechanism of the coordinate regulation of the levels (activities) of the isoaccepting tRNAs, corresponding aminoacyl-tRNA synthetases and mRNAs predominantly translated at a given moment of time can be suggested. Such a mechanism can ensure the needed accuracy of the protein folding process. Analysis of gene sequences of various pro- and eukaryotic organisms carried out in the present work revealed that the codon usage frequency spectra of simultaneously synthesized proteins are similar. The relative appearance of the most rare and frequent codons in investigated gene sequences displays a high degree of conservatism. It has also been found that structural-homologous proteins from different organisms (cytochromes c, myoglobins) have very similar codon frequency distribution profiles. This property retains despite the significant variations in the codon usage spectra in the investigated gene sequences. The data obtained indicate that the codon distribution in mRNAs whose diversity is mainly conditioned by the genetic code redundance is a program that determines translational rates of different mRNA parts thus controlling the spatial folding of the synthesized peptide chain.

Animals↗
PubMedDate not supplied

The distribution of codons by classes of triplets in the sequence of genes.

According to a criterion of symmetry-asymmetry, the triplets of the genetic code can be divided into four classes. In the genes of viruses and human mitochondria, the frequency by which a codon is followed by a codon of the same class is higher than that theoretically estimated. This is the consequence of the fact that in an initial stage of evolution many codons were duplicated.

Base Sequence↗
PubMed2006

Changing images of the gene.

During the twentieth century the gene emerged as the major driving force of biology. Initially, even the nature and behavior of gene vehicles, the chromosomes, were subjected to doubts. The basic or standard gene concept, as a unit of function, mutation, and recombination, had to be revised. Half a century was required for reaching a general consensus about the chemical nature of the genetic material, DNA and RNA. The relationship between single genes and individual proteins was a great milestone at the middle of the twentieth century, but within two decades it was realized that the relationship was more complex. Understanding of genetic coding, transcription, and translation during the 1960s laid a firm foundation to the "nucleic doctrine," harking back to the dicta of Lederberg (1959) and meaning that single nucleic acid genes alone were responsible for each separate function within the cell. However, important aspects of gene expression are recognized now as a function of the genome and many genes collaborate in circuits. It has come to light that genes may be mobile, exist in plasmids and cytoplasmic organelles, and can be imported by nonsexual means from other organisms or as synthetic products. Epigenetics has reborn as a new field of developmental genetics. The unorthodox prion proteins can even simulate some gene properties. Genetics was to an extent reincarnated as of the twenty-first century by assimilating the tools of cybernetics and of many formerly distant areas of science. This overview highlights some of the historical milestones that contributed to the development of our image of the gene, extending elements of issues laid down by Rédei (2003).

Alleles↗
PubMed1979

Nucleotide sequence of the 5' terminus of satellite tobacco necrosis virus ribonucleic acid.

Treatment of the RNA of satellite tobacco necrosis virus (STNV) with phosphomonoesterase followed by heat denaturation and treatment with polynucleotide kinase in the presence of [gamma-32P]ATP yields a STNV [5'-32P]RNA containing a homogeneous 5' terminus. Analyses of this STNV [5'-32P]RNA yield the sequence of the first 42 nucleotides from the 5'terminus of STNV RNA. This nucleotide sequence contains the translation initiation AUG codon starting at position 30 from the 5' terminus as indicated by match of subsequent nucleotides with the genetic code assignments for the N-terminal amino acids of STNV coat protein in the 5'-terminal sequence ppAGUAAAGACAGGAAACUU-UACUGACUAACAUGGCAAAACAAC. An interesting feature of this sequence is its potential to form a hairpin loop structure involving perfect Watson-Crick base pairing between the first seven nucleotides and nucleotides at positions 16--22.

Base Sequence↗
PubMed1985

Rationalization of some genetic anticodonic assignments.

The genetic code appears to be a logic matrix in which, generally speaking, there is a correlation between the hydrophobicities of amino acids and their anticodonic nucleotides. There are several exceptions to this generality, however, and using previous data on hydrophobicity and binding constants, coupled with new data on reaction rates, we rationalize several of the anticodonic assignments.

Amino Acids↗
PubMed1998

The hypotrichous ciliate Euplotes octocarinatus has only one type of tRNACys with GCA anticodon encoded on a single macronuclear DNA molecule.

Deviations from the universal genetic code have evolved independently several times in ciliated protozoa. Thus, in some species UAA and UAG are no longer used as termination codons, but are read as glutamine, whereas in the genus Euplotes , UGA is translated as cysteine. We have investigated the nature of the tRNACys isoacceptor responsible for decoding UGA in Euplotes cells. Southern hybridization analyses indicated that a single DNA molecule of 630 bp encoding tRNACys exists in the macronucleus of Euplotes octocarinatus . Cloning and sequencing of this fragment revealed that it contains only one copy of a tRNACys gene, which codes for a normal tRNACys with GCA anticodon. This is the first report of the characterization of a tRNA gene in any hypotrichous ciliate. It contains putative signals for initiation and termination of transcription by RNA polymerase III and can be transcribed efficiently in vitro in HeLa cell nuclear extract. Intensive studies on the DNA and tRNA level involving PCR analyses have not disclosed the existence of any tRNA Cys isoacceptor with UCA or ICA anticodons. Translation of the UGA codon by tRNA sub GCA sup Cys necessitates a G:A mispairing in the first anticodon position. We discuss a number of aspects which might contribute to the finding that a near-cognate tRNA isoacceptor efficiently translates the UGA stop codon.

Animals↗
PubMedDate not supplied

Deterministic hypotheses on the origin of life and of its reproduction.

The current theory of the origin of life by random polymerisation and selection of nucleic acids is challenged by the hypothesis that the primitive enzymatic sites would have been formed by abiotic polymerisation of aminoacids, specifically gathered (by saline, hydrogen, or hydrophobic interactions), around the different substrates. The information contained in these proteinoids would have been transferred to messenger-like RNAs by a mechanism reverse of that of the present protein synthesis, and then to DNA. The interactions between aminoacids and nucleotidic sequences would have been at the origin of the genetic code, as hypothesized by several authors. We propose that the specificity of the bindings would have been enhanced and 'frozen' by ternary associations with specific proteinoids (future aminoacyl tRNA synthetases). The role of chance would have been limited to the supply of the products and to the determination of the conditions of reaction. Thermodynamic considerations (dissipation of the free enthalpy through enzymatic activities) may explain the emergence of the biological systems.

Binding Sites↗
PubMed1973

Reinitiation of a lac repressor fragment at a codon other than AUG.

52 Spontaneous nonsense mutants in the lac i gene of Escherichia coli were isolated and characterized. All mutants located early in the gene show negative complementation in vivo with a wild-type i gene in a recA diploid strain. In vitro studies show that those mutants that display negative complementing activity in vivo also make lac repressor fragments retaining inducer binding and immunological crossreactivity with wild-type repressor. Amino-acid sequence analysis of these fragments shows that they arise by reinitiation at internal sities of the i message after chain termination at a prior amber or ochre codon. There are at least two different internal reinitiation sites in the first 200 nucleotides of the translated part of the i message. The first site corresponds to the first internal in phase AUG codon, which specifies the methionine residue at position 42 of the repressor protein. This site can be activated by an amber codon, 45 nucleotides before the AUG codon. The second site is only 60 nucleotides past the first site and can be activated by an amber mutation derived from residue 60 of the protein. The second initiation codon specifies the amino-acid leucine in the wild-type repressor, but the reinitiated fragment shows an amino-terminal methionine residue at this position. Therefore, the second initiation site seems to involve an in vivo ambiguity of the genetic code in that the same codon can be translated into two different amino acids depending on the recognition of this codon during initiation (when methionine is inserted) or elongation of protein synthesis (when leucine is inserted). The possibility that a codon other than AUG can act as an initiation codon in vivo is discussed.

Adenine Nucleotides↗
PubMed1978

[Function of arginine in enzymes].

The average arginine content of proteins is 3.9%. Its frequency among the 20 amino acids of the proteins (13th position) is far lower than would be anticipated from the fact that 6 of the 61 codons for amino acids in the genetic code are arginine codons. Possible explanations for the relatively low frequency of arginine in proteins are discussed. The chemical and physicochemical properties of arginine, which are determined by the guanido group, and the method for chemical modification of arginine residues in proteins are described. The most important function of arginine residues in enzymes seems to be the recognition, binding, and orientation of anionic substrates and cofactors. This function is illustrated by numerous examples.

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↗
PubMed1991

Cloning and analysis of five mitochondrial tRNA-encoding genes from the fungus Beauveria bassiana.

Five mitochondrial (mt) tRNA genes from the filamentous fungus, Beauveria bassiana, were cloned and sequenced. The genes encoding the Val-, Ile-, Ser-, Trp- and Pro-accepting tRNAs were found clustered in the region 5' to the lrRNA-encoding gene. The genes were 64-77% homologous with the equivalent genes from other filamentous fungi, 49-58% to yeasts with the exception of the Val-accepting tRNA-encoding gene which was 76%, and only slightly homologous with Escherichia coli. The B. bassiana mt genetic code was found to be similar to that of other fungal mitochondria in that the UGA codon is used as a signal for Trp rather than as a stop codon. Transcript analysis has revealed that the genes present in tRNA cluster are transcribed and processed into tRNA-size products. Secondary structure models proposed for the gene products show that conservation of tRNA secondary structure also exists. The presence of a GGC sequence rather than a GGU sequence in the D-loop of the tRNA(Trp)-encoding gene is a feature unique to the B. bassiana mt tRNA. An unconventional G-A base pair present in the D-stem of the tRNA(Ser)-encoding gene is a feature conserved in the mt tRNA of other filamentous fungi. Comparison of the B. bassiana tRNA-encoding genes with those of two other filamentous fungi and two yeasts revealed that the differences between closely related species favoured transition-type mutations.

Base Sequence↗
PubMed2005

A computational method to predict genetically encoded rare amino acids in proteins.

In several natural settings, the standard genetic code is expanded to incorporate two additional amino acids with distinct functionality, selenocysteine and pyrrolysine. These rare amino acids can be overlooked inadvertently, however, as they arise by recoding at certain stop codons. We report a method for such recoding prediction from genomic data, using read-through similarity evaluation. A survey across a set of microbial genomes identifies almost all the known cases as well as a number of novel candidate proteins.

Amino Acid Sequence↗
PubMed1975

Linear and inverted repetitions in protein sequences.

An extensive search for internal regularities in amino acid sequences has been made, using both the genetic code and the relative frequencies of amino acid alternatives in homologous proteins. The two methods give very similar results and strongly suggest the occurrence of significant linear and inverted repetitions (similar sequences of opposite polarity) in several proteins. A hypothesis is developed to explain the occurrence of such internal regularities in proteins. This hypothesis is based on a process of duplication of an ancestral loop in which a symmetrical arrangement of amino acid allows stabilization by interaction between the amino acid side chains.

Amino Acid Sequence↗
PubMed1996

Structural mechanics of bent DNA.

The DNA molecule is a familiar object. It is often depicted in magazines and advertisements as a double helix, with the letters of the genetic code strung along the two spiral backbones and joined together in pairs. In such pictures the molecule is usually shown as straight; yet in the chromosomes of living organisms, DNA is curved and wound up into condensed packages. This article explains what is involved in such bending of DNA in the cell. It uses the ideas of structural mechanics--a tool of engineers--to show how the various components fit together when the molecule is bent.

Adenine↗
PubMed1995

Complete sequence of the mitochondrial DNA of the annelid worm Lumbricus terrestris.

We have determined the complete nucleotide (nt) sequence of the mitochondrial genome of an oligochaete annelid, the earthworm Lumbricus terrestris. This genome contains the 37 genes typical of metazoan mitochondrial DNA (mtDNA), including ATPase8, which is missing from some invertebrate mtDNAs. ATPase8 is not immediately upstream of ATPase6, a condition found previously only in the mtDNA of snails. All genes are transcribed from the same DNA strand. The largest noncoding region is 384 nt and is characterized by several homopolymer runs, a tract of alternating TA pairs, and potential secondary structures. All protein-encoding genes either overlap the adjacent downstream gene or end at an abbreviated stop codon. In Lumbricus mitochondria, the variation of the genetic code that is typical of most invertebrate mitochondrial genomes is used. Only the codon ATG is used for translation initiation. Lumbricus mtDNA is A + T rich, which appears to affect the codon usage pattern. The DHU arm appears to be unpaired not only in tRNAser(AGN), as is typical for metazoans, but perhaps also in tRNAser(UCN), a condition found previously only in a chiton and among nematodes. Relating the Lumbricus gene organization to those of other major protostome groups requires numerous rearrangements.

Amino Acid Sequence↗
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

Possible steps to the emergence of life: the [GADV]-protein world hypothesis.

Based on the fact that RNA has not only a genetic function but also a catalytic function, the RNA world theory on the origin of life was first proposed about 20 years ago. The theory assumes that RNA was amplified by self-replication to increase RNA diversity on the primitive earth. Since then, the theory has been widely accepted as the most likely explanation for the emergence of life. In contrast, we reached another hypothesis, the [GADV]-protein world hypothesis, which is based on pseudo-replication of [GADV]-proteins. We reached this hypothesis during studies on the origins of genes and the genetic code, where [G], [A], [D], and [V] refer to Gly, Ala, Asp, and Val, respectively. In this review, possible steps to the emergence of life are discussed from the standpoint of the [GADV]-protein world hypothesis, comparing it in parallel with the RNA world theory. It is also shown that [GADV]-peptides, which were produced by repeated dry-heating cycles and by solid phase peptide synthesis, have catalytic activities, hydrolyzing peptide bonds in a natural protein, bovine serum albumin. These experimental results support the [GADV]-protein world hypothesis for the origin of life.

Alanine↗