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PubMed1990

Genetic code 1990. Outlook.

The genetic code is evolving as shown by 9 departures from the universal code: 6 of them are in mitochondria and 3 are in nuclear codes. We propose that these changes are preceded by disappearance of a codon from coding sequences in mRNA of an organism or organelle. The function of the codon that disappears is taken by other, synonymous codons, so that there is no change in amino acid sequences of proteins. The deleted codon then reappears with a new function. Wobble pairing between anticodons and codons has evolved, starting with a single UNN anticodon pairing with 4 codons. Directional mutation pressure affects codon usage and may produce codon reassignments, especially of stop codons. Selenocysteine is coded by UGA, which is also a stop codon, and this anomaly is discussed. The outlook for discovery of more changes in the code is favorable, and open reading frames should be compared with actual sequential analyses of protein molecules in this search.

Anaerobiosis↗
PubMed2006

Gene conversion between direct noncoding repeats promotes genetic and phenotypic diversity at a regulatory locus of Zea mays (L.).

While evolution of coding sequences has been intensively studied, diversification of noncoding regulatory regions remains poorly understood. In this study, we investigated the molecular evolution of an enhancer region located 5 kb upstream of the transcription start site of the maize pericarp color1 (p1) gene. The p1 gene encodes an R2R3 Myb-like transcription factor that regulates the flavonoid biosynthetic pathway in maize floral organs. Distinct p1 alleles exhibit organ-specific expression patterns on kernel pericarp and cob glumes. A cob glume-specific regulatory region has been identified in the distal enhancer. Further characterization of 6 single-copy p1 alleles, including P1-rr (red pericarp/red cob) and P1-rw (red pericarp and white cob), reveals 3 distinct enhancer types. Sequence variations in the enhancer are correlated with the p1 gene expression patterns in cob glume. Structural comparisons and phylogenetic analyses suggest that evolution of the enhancer region is likely driven by gene conversion between long direct noncoding repeats (approximately 6 kb in length). Given that tandem and segmental duplications are common in both animal and plant genomes, our studies suggest that recombination between noncoding duplicated sequences could play an important role in creating genetic and phenotypic variations.

Alleles↗
PubMed1998

Rhyme or reason: RNA-arginine interactions and the genetic code.

Theories about the origin of the genetic code require specific recognition between nucleic acids and amino acids at some stage of the code's evolution. A statistical analysis of arginine-binding RNA aptamers now offers the opportunity to test such interactions and provides the strongest support for an intrinsic affinity between any amino acid and its codons.

Animals↗
PubMed2003

Elucidation of tRNA-dependent editing by a class II tRNA synthetase and significance for cell viability.

Editing of misactivated amino acids by class I tRNA synthetases is encoded by a specialized internal domain specific to class I enzymes. In contrast, little is known about editing activities of the structurally distinct class II enzymes. Here we show that the class II alanyl-tRNA synthetase (AlaRS) has a specialized internal domain that appears weakly related to an appended domain of threonyl-tRNA synthetase (ThrRS), but is unrelated to that found in class I enzymes. Editing of misactivated glycine or serine was shown to require a tRNA cofactor. Specific mutations in the aforementioned domain disrupt editing and lead to production of mischarged tRNA. This class-specific editing domain was found to be essential for cell growth, in the presence of elevated concentrations of glycine or serine. In contrast to ThrRS, where the editing domain is not found in all three kingdoms of living organisms, it was incorporated early into AlaRSs and is present throughout evolution. Thus, tRNA-dependent editing by AlaRS may have been critical for making the genetic code sufficiently accurate to generate the tree of life.

Adenosine Triphosphate↗
PubMed1989

A unified matrix hypothesis of DNA-directed morphogenesis, protodynamism and growth control.

A theoretical concept is proposed, in order to explain some enigmatic aspects of cellular and molecular biology of eukaryotic organisms. Among these are the C-value paradox of DNA redundancy, the correlation of DNA content and cell size, the disruption of genes at DNA level, the "Chromosome field" data of Lima de Faria (Hereditas 93:1, 1980), the "quantal mitosis" proposition of Holtzer et al. (Curr. Top. Dev. Biol. 7:229 1972), the inheritance of morphological patterns, the relations of DNA and chromosome organisation to cellular structure and function, the molecular basis of speciation, etc. The basic proposition of the "Unified Matrix Hypothesis" is that the nuclear DNA has a direct morphogenic function, in addition to its coding function in protein synthesis. This additional genetic information is thought to be largely contained in the non-protein coding transcribed DNA, and in the untranscribed part of the genome.

Animals↗
PubMed2006

Evolution of proteomes: fundamental signatures and global trends in amino acid compositions.

BACKGROUND: The evolutionary characterization of species and lifestyles at global levels is nowadays a subject of considerable interest, particularly with the availability of many complete genomes. Are there specific properties associated with lifestyles and phylogenies? What are the underlying evolutionary trends? One of the simplest analyses to address such questions concerns characterization of proteomes at the amino acids composition level. RESULTS: In this work, amino acid compositions of a large set of 208 proteomes, with significant number of representatives from the three phylogenetic domains and different lifestyles are analyzed, resorting to an appropriate multidimensional method: Correspondence analysis. The analysis reveals striking discrimination between eukaryotes, prokaryotic mesophiles and hyperthemophiles-themophiles, following amino acid usage. In sharp contrast, no similar discrimination is observed for psychrophiles. The observed distributional properties are compared with various inferred chronologies for the recruitment of amino acids into the genetic code. Such comparisons reveal correlations between the observed segregations of species following amino acid usage, and the separation of amino acids following early or late recruitment. CONCLUSION: A simple description of proteomes according to amino acid compositions reveals striking signatures, with sharp segregations or on the contrary non-discriminations following phylogenies and lifestyles. The distribution of species, following amino acid usage, exhibits a discrimination between [high GC]-[high optimal growth temperatures] and [low GC]-[moderate temperatures] characteristics. This discrimination appears to coincide closely with the separation of amino acids following their inferred early or late recruitment into the genetic code. Taken together the various results provide a consistent picture for the evolution of proteomes, in terms of amino acid usage.

Amino Acids↗
PubMed2004

Regulation of RNA function by aminoacylation and editing?

The chemical modification of nucleic acids is a ubiquitous phenomenon. Aminoacylation of tRNAs by aminoacyl-tRNA synthetases (ARSs) is a reaction essentially devoted to protein synthesis but it is used also as an emergency mechanism to recycle stalled ribosomes, and it is required for genome replication in some RNA viruses. In several aminoacyl-tRNA synthetases a correction mechanism known as editing is present to prevent aminoacylation errors. Genome data reveal a growing number of open reading frames encoding ARS-like proteins. This strongly suggests the existence of a widespread and nonconventional machinery for aminoacylation and editing. Here we review the different biological functions of aminoacylation and editing; also we propose an evolutionary scenario for the origin of these two reactions, and hypothesize an extant role for RNA charging and editing outside the genetic code.

Amino Acyl-tRNA Synthetases↗
PubMed1990

Organization of the mitochondrial genome of Atlantic cod, Gadus morhua.

The mitochondrial DNA (mtDNA) from the Atlantic cod, Gadus morhua, was mapped using 11 different restriction enzymes and cloned into plasmid vectors. Sequence data obtained from more than 10 kilobases of cod mtDNA show that the genome organization, genetic code, and the overall codon usage have been conserved throughout the evolution of vertebrates. Comparison of the derived amino acid sequences of proteins encoded by cod mtDNA to the ones encoded by Xenopus laevis mtDNA revealed that the amino acid identity range from 46% to 93% for the different proteins. ND4L is most divergent while COI is most conserved. GUG was found as the translation initiation codon of the COI gene, indicating a dual coding function for this codon. The sequences of the 997 base pair displacement-loop (D-loop)-containing region and the origin of L-strand replication (oriL), are presented. Only few of the primary and secondary structure features found to be conserved among mammalian mitochondrial D-loops, can be identified in cod. Presence of CSB-2 in the D-loop-containing region and the conserved hairpin structure at oriL, indicates that replication of bony fish mtDNA may follow the same general scheme as described for higher vertebrates.

Amino Acid Sequence↗
PubMed1997

Isomorphism between cell and human languages: molecular biological, bioinformatic and linguistic implications.

The concept of cell language has been defined in molecular terms. The molecule-based cell language is shown to be isomorphic with the sound- and visual signal-based human language with respect to ten out of the 13 design features of human language characterized by Hockett. Biocybernetics, a general molecular theory of living systems developed over the past two and a half decades, is found to provide a physical theory underlying the phenomenon of cell language. The concept of cell language integrates bioenergetics and bioinformatics on the one hand and reductionistic and holistic experimental data on the other to account for living processes on the molecular level. The isomorphism between cell and human languages suggests that the DNA of higher eucaryotes contains two classes of genes--structural genes corresponding to the lexicon and 'spatiotemporal genes' corresponding to the grammar of cell language. The former is located in coding regions of DNA and the latter is predicted to reside primarily in noncoding regions. The grammar of cell language is identified with the mapping of the nucleotide sequences of DNA onto its 4-dimensional folding patterns that control the spatiotemporal evolution of gene expression. Such a mapping has been referred to as the second genetic code, in contrast to the first genetic code which maps nucleotide triplets onto amino acids. The cell language theory introduces into biology the linguistic principle of 'rule-governed creativity,' leading to the formulation of the concept of 'rule-governed creative molecules' or 'creations.' This concept sheds new light on molecular biology, bioinformatics, protein folding, and developmental biology. In addition, the cell language theory suggests that human language is ultimately founded on cell language.

Cell Biology↗
PubMed1997

Molecular characterization of the glyceraldehyde-3-phosphate dehydrogenase gene of Phaffia rhodozyma.

The glyceraldehyde-3-phosphate dehydrogenase (GPD; EC1.2.1.12)-encoding gene (gpd) was isolated from a genomic library of Phaffia rhodozyma CBS 6938. Unlike some other eukaryotic organisms the gpd gene is represented by a single copy in P. rhodozyma. The complete nucleotide sequence of the coding, as well as the flanking non-coding regions was determined. The nucleotide sequence of gpd predicted six introns and a polypeptide chain of 339 amino acids. The codon usage in the gpd gene of P. rhodozyma was highly biased and was significantly different from the codon usage in other yeasts. Phylogenetic analysis of different yeasts and filamentous asco- and basidiomycetes gpd sequences indicated that the gpd gene of P. rhodozyma forms a cluster with the corresponding genes of filamentous basidiomycetes.

Amino Acid Sequence↗
PubMed2005

Codon bias and noncoding GC content correlate negatively with recombination rate on the Drosophila X chromosome.

The patterns and processes of molecular evolution may differ between the X chromosome and the autosomes in Drosophila melanogaster. This may in part be due to differences in the effective population size between the two chromosome sets and in part to the hemizygosity of the X chromosome in Drosophila males. These and other factors may lead to differences both in the gene complements of the X and the autosomes and in the properties of the genes residing on those chromosomes. Here we show that codon bias and recombination rate are correlated strongly and negatively on the X chromosome, and that this correlation cannot be explained by indirect relationships with other known determinants of codon bias. This is in dramatic contrast to the weak positive correlation found on the autosomes. We explored possible explanations for these patterns, which required a comprehensive analysis of the relationships among multiple genetic properties such as protein length and expression level. This analysis highlights conserved features of coding sequence evolution on the X and the autosomes and illuminates interesting differences between these two chromosome sets.

Animals↗
PubMed1992

The mitochondrial genomes of two nematodes, Caenorhabditis elegans and Ascaris suum.

The nucleotide sequences of the mitochondrial DNA (mtDNA) molecules of two nematodes, Caenorhabditis elegans [13,794 nucleotide pairs (ntp)], and Ascaris suum (14,284 ntp) are presented and compared. Each molecule contains the genes for two ribosomal RNAs (s-rRNA and l-rRNA), 22 transfer RNAs (tRNAs) and 12 proteins, all of which are transcribed in the same direction. The protein genes are the same as 12 of the 13 protein genes found in other metazoan mtDNAs: Cyt b, cytochrome b; COI-III, cytochrome c oxidase subunits I-III; ATPase6, Fo ATPase subunit 6; ND1-6 and 4L, NADH dehydrogenase subunits 1-6 and 4L: a gene for ATPase subunit 8, common to other metazoan mtDNAs, has not been identified in nematode mtDNAs. The C. elegans and A. suum mtDNA molecules both include an apparently noncoding sequence that contains runs of AT dinucleotides, and direct and inverted repeats (the AT region: 466 and 886 ntp, respectively). A second, apparently noncoding sequence in the C. elegans and A. suum mtDNA molecules (109 and 117 ntp, respectively) includes a single, hairpin-forming structure. There are only 38 and 89 other intergenic nucleotides in the C. elegans and A. suum mtDNAs, and no introns. Gene arrangements are identical in the C. elegans and A. suum mtDNA molecules except that the AT regions have different relative locations. However, the arrangement of genes in the two nematode mtDNAs differs extensively from gene arrangements in all other sequenced metazoan mtDNAs. Unusual features regarding nematode mitochondrial tRNA genes and mitochondrial protein gene initiation codons, previously described by us, are reviewed. In the C. elegans and A. suum mt-genetic codes, AGA and AGG specify serine, TGA specifies tryptophan and ATA specifies methionine. From considerations of amino acid and nucleotide sequence similarities it appears likely that the C. elegans and A. suum ancestral lines diverged close to the time of divergence of the cow and human ancestral lines, about 80 million years ago.

Amino Acid Sequence↗
PubMed2000

Quadruplet codons: implications for code expansion and the specification of translation step size.

One of the requirements for engineering expansion of the genetic code is a unique codon which is available for specifying the new amino acid. The potential of the quadruplet UAGA in Escherichia coli to specify a single amino acid residue in the presence of a mutant tRNA(Leu) molecule containing the extra nucleotide, U, at position 33.5 of its anticodon loop has been examined. With this mRNA-tRNA combination and at least partial inactivation of release factor 1, the UAGA quadruplet specifies a leucine residue with an efficiency of 13 to 26 %. The decoding properties of tRNA(Leu) with U at position 33.5 of its eight-membered anticodon loop, and a counterpart with A at position 33.5, strongly suggest that in both cases their anticodon loop bases stack in alternative conformations. The identity of the codon immediately 5' of the UAGA quadruplet influences the efficiency of quadruplet translation via the properties of its cognate tRNA. When there is the potential for the anticodon of this tRNA to dissociate from pairing with its codon and to re-pair to mRNA at a nearby 3' closely matched codon, the efficiency of quadruplet translation at UAGA is reduced. Evidence is presented which suggests that when there is a purine base at position 32 of this 5' flanking tRNA, it influences decoding of the UAGA quadruplet.

Amino Acid Sequence↗
PubMed2000

Origin of life on earth and Shannon's theory of communication.

The genetic information system is segregated, linear and digital. It is astonishing that the technology of information theory and coding theory has been in place in biology for at least 3.850 billion years (Mojzsis, S.J., Kishnamurthy, Arrhenius, G., 1998. Before RNA and after: geological and geochemical constraints on molecular evolution 1-47. In: Gesteland, R.F. (Ed.), The RNA World: The Nature of Modern RNA Suggests a Prebiotic RNA, second ed. Cold Spring Harbor Laboratory Press, Boca Raton, FL). The genetic code performs a mapping between the sequences of the four nucleotides in mRNA to the sequences of the 20 amino acids in protein. It is highly relevant to the origin of life that the genetic code is constructed to confront and solve the problems of communication and recording by the same principles found both in the genetic information system and in modern computer and communication codes. There is nothing in the physico-chemical world that remotely resembles reactions being determined by a sequence and codes between sequences. The existence of a genome and the genetic code divides living organisms from non-living matter. If the historic process of the origin and evolution of life could be followed, it would prove to be a purely chemical process (Wächtershäuser, G., 1997. The origin of life and its methodological challenge. J. Theor. Biol. 187, 483-694). The question is whether this historic process or any reasonable part of it is available to human experiment and reasoning; there is no requirement that Nature's laws be plausible or even known to mankind. Bohr (Bohr, N., 1933. Light and life. Nature 308, 421-423, 456-459) argued that life is consistent with but undecidable by human reasoning from physics and chemistry. Perhaps scientists will come closer and closer to the riddle of how life emerged on Earth, but, like Zeno's Achilles, never achieve a complete solution.

Genetic Code↗
PubMed1978

Immunologic approaches toward detection of type C viral expression in man.

Type C RNA viruses have been isolated from a large number of mammalian species. These agents may be horizontally transmitted as infectious cancer-inducing agents, or vertically transmitted from one generation to the next, often in an unexpressed form, within the host genome. To date, the translational products of three viral genes have been identified. With purified virus-coded proteins as probes, sensitive and highly specific radioimmunologic assays have been developed for the detection of antibodies and antigens related to the known type C viruses. These techniques have proved valuable in sero-epidemiologic studies of the horizontally transmitted oncogenic viruses of cats, cattle, and gibbons, and have been used to detect translational products of endogenous viruses in tissues of species from which complete virus has yet to be isolated. This review describes the application of radioimmunoassays in the search for immunologic evidence of type C virus expression in man.

Animals↗