Characterization of genetic coding changes in bacteria produced by ionizing radiation and by the radioactive decay of incorporated 3 H-labelled compounds.
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Amino Acids↗
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Isolation of a rat mitochondrial release factor. Accommodation of the changed genetic code for termination.
A single release factor has been isolated and partially purified from rat mitochondria. It requires ethanol in addition to the specific termination codon when assayed in a heterologous system with Escherichia coli ribosomes. The factor recognizes the codons UAA and UAG but not UGA, and therefore it has been designated mtRF-1. A factor of the bacterial RF-2 type, which in E. coli recognizes UGA, or of the mammalian type, which recognizes all three termination codons, has not been detected in mitochondria. The absence of a factor responding to UGA accommodates the use of this codon as a signal for tryptophan in the rat mitochondrial genetic code. The mtRF-1 could translate all of the known termination codons in the rat mitochondrial genome. It does not respond to AGG and AGA which in bovine and human mitochondrial DNA code for termination but which in rat mitochondria may not code for either an amino acid or for termination.
Animals↗
The evolution of the plastid genomes in the holoparasitic Balanophoraceae.
The independent transition to a heterotrophic lifestyle in plants drove remarkably convergent evolutionary trajectories, characterized by morphological modifications and reductions in their plastomes. The characteristics of the minimum plastome required for survival, if they exist, remain a topic of debate. The holoparasitic family Balanophoraceae was initially presumed to have entirely lost their plastids, however, recent reports revealed the presence of reduced and aberrant plastids with odd genomes. Among the outstanding features of these genomes are the highest nucleotide composition bias across the tree of life and the only two genetic code changes ever recorded among plants. In this study, we assembled the plastomes from five genera, four of which had never been studied. Major common features include extremely high AT content, the lack of a typical quadripartite structure and extensive size reduction due to gene elimination and genome compaction. The family exhibits multiple gene and intron losses, and a broad range of scenarios regarding the evolution of the plastid trnE, a gene considered essential because of its dual function in tetrapyrrole biosynthesis and translation within the plastid. In addition, phylogenetic analyses suggest that the genus Scybalium is not monophyletic. An evolutionary model for the plastomes of the Balanophoraceae is proposed.
Genome, Plastid↗
Differential use of termination codons in ciliated protozoa.
Sequence analysis of genes in four species of ciliated protozoa and analysis of tRNAs in Tetrahymena has demonstrated that TAG and TAA encode glutamine or glutamic acid in these organisms and TGA is the only stop codon. Thus, it has generally been assumed that all ciliates use a nonuniversal genetic code in which TGA acts as the sole termination codon. We have sequenced the linear DNA molecules that carry an actin gene and a beta-tubulin gene from the ciliate Euplotes crassus. These genes are shown to use TAA as a termination codon based on homology to known actin and beta-tubulin gene sequences. In addition, we have sequenced a portion of the 3' terminus of the E. crassus H4 histone gene and show that it also uses TAA as a termination codon. These data indicate that the timing of genetic code changes in the ciliates must be reconsidered.
Actins↗
Evolutionary changes in the genetic code.
The genetic code has been influenced by directional mutation pressure affecting the base composition of DNA, sometimes in the direction of increased GC content and at other times, in the direction of AT. Such pressure led to changes in species-specific usages of codons and tRNA anticodons, and also in amino acid assignments of codons in mitochondria and in several intact organisms. These code changes are probably recent evolutionary events. The genetic code is not 'frozen', but instead it is still evolving.
Base Sequence↗
The role of ribosomal conformation in protein biosynthesis: the streptomycin-ribosome interaction.
The role played by ribosomal conformation in codon-anticodon recognition has been studied using streptomycin as a probe, inasmuch as streptomycin is known to cause misreading of the genetic code. Changes in ribosomal structure have been followed by the method of hydrogen-tritium exchange. The results show that streptomycin induces two types of change in the hydrogen exchange pattern. At low molar ratios of streptomycin to ribosomes, a stimulation of the hydrogen exchange rate ("loosening" of ribosomal structure) is observed, with a small inhibition of polypeptide synthesis. As the streptomycin: ribosome ratio is increased, a maximum exchange rate is reached, after which the rate decreases ("tightening" of structure); in this region, inhibition of peptide synthesis increases sharply, and misreading of the code begins. None of these effects is observed with streptomycin-resistant ribosomes.
Escherichia coli↗
A change in the genetic code in Mycoplasma capricolum.
Mycoplasma capricolum was previously found to use UGA instead of UGG as its codon for tryptophan and to contain 75% A + T in its DNA. The codon change could have been due to mutational pressure to replace C + G by A + T, resulting in the replacement of UGA stop codons by UAA, change of the anticodon in tryptophan tRNA from CCA to UCA, and replacement of UGG tryptophan codons by UGA. None of these changes should have been deleterious.
Anticodon↗
A quantitative measure of error minimization in the genetic code.
We have calculated the average effect of changing a codon by a single base for all possible single-base changes in the genetic code and for changes in the first, second, and third codon positions separately. Such values were calculated for an amino acid's polar requirement, hydropathy, molecular volume, and isoelectric point. For each attribute the average effect of single-base changes was also calculated for a large number of randomly generated codes that retained the same level of redundancy as the natural code. Amino acids whose codons differed by a single base in the first and third codon positions were very similar with respect to polar requirement and hydropathy. The major differences between amino acids were specified by the second codon position. Codons with U in the second position are hydrophobic, whereas most codons with A in the second position are hydrophilic. This accounts for the observation of complementary hydropathy. Single-base changes in the natural code had a smaller average effect on polar requirement than all but 0.02% of random codes. This result is most easily explained by selection to minimize deleterious effects of translation errors during the early evolution of the code.
Amino Acids↗
Periodical changes of amino acid reactivity within the genetic code.
Enthalpies (delta H++) and entropies (delta S++) of activation for the reaction of 18 N'-hydroxysuccinimide esters of N-protected proteinaceous amino acids with p-anisidine were measured and free enthalpies of activation (delta G++) at 25 degrees C were calculated on this basis. A regular correlation between delta G++s and the corresponding amino acid codons was found. To obtain this correlation all the codons had to be arranged in a closed ring in which the consecutive codons were connected by one-step mutational changes. One-step mutations appeared as a regular series: 2,3,3,3,1,3,3,3,1,3,3,3,1,3,3,3,2,3,3,3. (the numbers denote a codon position in which a change took place). There were three such 'one-step mutation periods' in the ring, each containing 20 codons (in each block of 16 codons with A, U and C, in the central position and 4 codons containing G in the central position). The end of the third period (UG) and the beginning of the first period were bridged by the four codons of glycine with G in the second position. The values of delta G++ change similarly in each period, increasing upon approaching Lys, Pro, and Ile. The periodical relation between the chemical reactivities of the coded amino acids (reflected by delta G++s) and the structure of their codons could be of importance for the origin of the genetic code i.e. for selection of proper codons for the definite amino acids.
Amino Acid Sequence↗
Isolation and characterization of multiple forms of ovine pancreatic deoxyribonuclease. Chromatograhpic behavior of the enzyme on concanavalin A-agarose and carboxymethylcellulose columns.
A new procedure has been devised for the purification of ovine DNase, including (NH/4)2SO4 fractionation, two steps of CM-cellulose chromatography, concanavalin A-agarose chromatography, and gel filtration on Sephadex G--100. The enzyme, like bovine DNase, exhibits multiplicity due to changes in the primary structure and the sugar structure of the carbohydrate moiety. Unlike bovine DNase, ovine DNase does not have sialic acid in any of its multiple forms. Concanavalin A-agarose is useful in the purification of not only ovine but also bovine DNase. For ovine DNase, it is a necessary and key step of purification; for bovine DNase, it can be used to purify commercial preparations of DNase free from proteases in a single step as judged by its stability in Ca2+-free media at pH 8.0. The purified enzyme has a specific activity equal to that of a highly purified DNase and presumably contains predominantly DNases A and C. Two of the four forms of ovine DNase have been purified to apparent homogeneity and subjected to chemical analysis. The present results show that bovine and ovine DNases have indistinguishable molecular weights and identical end groups, suggesting that they may have the same number of amino acid residues. The amino acid composition indicates that two enzymes may have six residues of amino acids subject to substitution which can be explained by single base changes in their genetic code words. Amino acid analyses also indicate that the most likely difference between two forms of ovine DNase is the substitution of Leu for Arg.
Amino Acids↗
[Environmental carcinogens: mechanisms of action and occurrence. Some aspects (author's transl)].
New aspects on the mechanism of action of known environmental carcinogens are described. These compounds are not active as such, but are bioactivated in the mammalian metabolism via chemically reactive intermediates to electrophilic reactants, forming with information-bearing biopolymeres covalent bonds. This change in the genetic code is in agreement with the mutation hypothesis of carcinogenesis. Aflatoxin B1, N-nitroso compounds and benzo(a)pyrene are taken as examples. "Threshold levels", e.g. no-effect-levels derived from animal experiments with all their inherent limitations, are compared with data from human exposure to benzo(a)pyren, aflatoxine, N-nitroso compounds and vinyl chloride. The difficulties of such risk evaluations are discussed.
Aflatoxins↗
Structural convergence during protein evolution.
Several recent protein crystallographic structure determinations have demonstrated the existence of considerable tertiary structural similarity among proteins otherwise having little similarity in either amino acid sequence or biological function. In order to assess the possibility that such proteins may have arisen through processes of divergent evolution from a common ancestor, a graphical presentation is given which correlates the pattern of allowed single base substitutions defined by the genetic code with the associated changes in the structural properties of the encoded amino acids. The results show that while a large degree of structural conservation is evident due to codon synonomy, there is, in general, little tendency for the code to be structurally conservative in the majority of the cases where codon single-base changes result in amino acid substitutions. The possible consequences of this pattern of potential amino acid substitutions are discussed in relation to protein evolutionary processes.
Amino Acids↗
The genetic code in mitochondria and chloroplasts.
The universal genetic code is used without changes in chloroplasts and in mitochondria of green plants. Non-plant mitochondria use codes that include changes from the universal code. Chloroplasts use 31 anticodons in translating the code; a number smaller than that used by bacteria, because chloroplasts have eliminated 10 CNN anticodons that are found in bacteria. Green plant mitochondria (mt) obtain some tRNAs from the cytosol, and genes for some other tRNAs have been acquired from chloroplast DNA. The code in non-plant mt differs from the universal code in the following usages found in various organisms: UGA for Trp, AUA for Met, AGR for Ser and stop, AAA for Asn, CUN for Thr, and possibly UAA for Tyr. CGN codons are not used by Torulopsis yeast mt. Non-plant mt, e.g. in vertebrates, may use a minimum of 22 anticodons for complete translation of mRNA sequences. The following possible causes are regarded as contributing to changes in the non-plant mt: directional mutation pressure, genomic economization, changes in charging specificity of tRNAs, loss of release factor RF2, changes in RF1, changes in anticodons, loss of lysidine-forming enzyme system, and disappearance of codons from coding sequences.
Animal Population Groups↗
Mutation of the p53 gene in human acute myelogenous leukemia.
Heterogeneity of p53 protein expression is seen in blast cells of patients with acute myelogenous leukemia (AML). p53 protein is detected in the blasts of certain AML patients but not in others. We have identified p53 protein variants with abnormal mobility on gel electrophoresis and/or prolonged half-life (t 1/2). We have sequenced the p53 coding sequence from primary blast cells of five AML patients and from the AML cell line (OCIM2). In OCIM2, a point mutation in codon 274 was identified that changes a valine residue to aspartic acid. A wild type p53 allele was not detected in these cells. Two point mutations (codon 135, cysteine to serine; codon 246, methionine to valine) were identified in cDNA from blasts of one AML patient. Both mutations were present in blast colonies grown from single blast progenitor cells, indicating that individual leukemia cells had sustained mutation of both p53 alleles. The cDNAs sequenced from blast samples of four other patients, including one with prolonged p53 protein t 1/2 and one with no detectable p53 protein, were fully wild type. Thus, the heterogeneity of p53 expression cannot be explained in all cases by genetic change in the p53 coding sequence. The prolonged t 1/2 of p53 protein seen in some AML blasts may therefore reflect changes not inherent to p53. A model is proposed in which mutational inactivation of p53, although not required for the evolution of neoplasia, would confer a selective advantage, favoring clonal outgrowth during disease progression.
Base Sequence↗
The satellite Tobacco Necrosis Virus in studies of genetic coding.
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Amino Acid Sequence↗
Amino acid composition of proteins as a product of molecular evolution.
The average amino acid composition of proteins is determined by the genetic code and by random base changes in evolution. Small but significant deviations from expected composition can be explained by selective constraint on amino acid substitutions. In particular, the deficiency of arginine in proteins has been caused by constraint, during evolution, on fixation of mutations substituting arginine for other amino acids.
Amino Acids↗
Evolution of the mitochondrial genetic code. III. Reassignment of CUN codons from leucine to threonine during evolution of yeast mitochondria.
Yeast mitochondria use UUR as the sole leucine codons. CUN, universal leucine codons, are read as threonine by aberrant threonine tRNA with anticodon sequence (UAG). The reassignment of CUN codons to threonine during yeast mitochondrial evolution could have proceeded by the disappearance of CUN codons from the reading frames of messenger RNA, through mutation mainly to UUR leucine codons as a result of AT pressure. We suggest that this was accompanied by a loss of leucine-accepting ability of tRNA Leu(UAG). This tRNA could have then acquired threonine-accepting activity through the appearance of an additional threonyl-tRNA synthetase. CUN codons that subsequently appeared from mutations of various other codons would have been translated as threonine. This change in the yeast mitochondrial genetic code is likely to have evolved through a series of nondisruptive nucleotide substitutions that produced no widespread replacement of leucine by threonine in proteins as a consequence.
Adenine↗
Construction of interleukin-1 alpha mutants using unequal contamination of synthetic oligonucleotides.
Proteins without readily available three-dimensional structural data present a difficult problem in the exploration of structure/function relationships. Saturation mutagenesis using contaminated oligonucleotides can identify potentially interesting regions of such a protein. This technique, in which synthesized oligonucleotides contain low-level base substitutions, allows random mutations to be placed throughout a gene sequence. Using double-stranded cassettes, a region of the human interleukin-1 alpha gene has been altered using such mutagenic oligonucleotides. However, instead of contaminating both strands of the gene sequence at the same level, each strand of the insert was contaminated at a different level. Several recombinants were sequenced and the effects of the mutations on the activity of the proteins were examined. Contaminating the two oligonucleotides at different levels produced a significantly different distribution of nucleotide changes from that seen if both strands were contaminated at the same level. The observed distribution followed the average of the distributions for each of the two contamination levels. This resulted in roughly equal frequencies of 1 to 5 nucleotide changes per clone with very few clones containing the wild-type nucleotide sequence. This helped overcome the redundancy in the genetic code, resulting in a high frequency of amino acid changes, and allowed changes at every amino acid to be sampled in a small number of mutants. This procedure can allow a gene sequence to be screened rapidly by removing most wild-type sequences from analysis while making sure that there are many amino acid changes in the resultant mutants.
Amino Acid Sequence↗