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PubMed1982

[Evolutionary changes in the genetic code, predictable on basis of the hypothesis of physical predetermination of the structure of codon bases].

According to the earlier proposed hypothesis on the structural correspondence between amino acids and doublets from the first codon bases (Sukhodolets 1980), the UGA triplet corresponds to tryptophan and the AGX triplets - to the termination codons. It is notably this sense of the UGA and AGA, AGG, respectively, that was reported for mitochondrial codes. Thereby, a proposal is indirectly confirmed that meanings of the UGA (nonsense) and AGA, AGG (arginine) in the normal cytoplasmic code is the result of evolutionary changes.

Amino Acids↗
PubMed1993

Evolutionary changes in the genetic code.

1. The genetic code was thought to be identical ("universal") in all biological systems until 1981, when it was discovered that the coding system in mammalian mitochondria differed from the universal code in the use of codons AUA, UGA, AGA and AGG. 2. Many other differences have since been discovered, some in mitochondria of various phyla, others in bacteria, ciliated protozoa, algae and yeasts. 3. The original thesis that the code was universal and "frozen" depended on the precept that any mutational change in the code would be lethal, because it would produce widespread alterations in the amino acid sequences of proteins. Such changes would destroy protein function, and hence would be intolerable. 4. The objection was "by-passed" by nature. It is possible for a codon to disappear from mRNA molecules, often as a result of directional mutation pressure in DNA: thus all UGA stop codons can be replaced by UAA. 5. The missing UGA codon can then reappear when some UGG tryptophan codons mutate to UGA. The new UGA codons will be translated as tryptophan, as is the case in non-plant mitochondria and Mycoplasma. Therefore, no changes have taken place in the amino acid sequences of proteins. 6. Variations of this procedure have occurred, affecting various codons, and discoveries are still being made. The findings illustrate the evolutionary interplay between tRNA, release factors and codon-anticodon pairing.

Animals↗
PubMed1993

The evolutionary change of the genetic code as restricted by the anticodon and identity of transfer RNA.

The discovery of non-universal genetic codes in several mitochondria and nuclear systems during the part ten years has necessitated a reconsideration of the concept that the genetic code is universal and frozen, as was once believed. Here, the flexibility of the relationship between codons and amino acids is discussed on the basis of the distribution of non-universal genetic codes in various organisms insofar as has been observed to date. Judging from the result of recent investigations into tRNA identity, it would appear that the non-participation of the anticodon in recognition by aminoacyl-tRNA synthetase has significantly influenced the variability of codons.

Animals↗
PubMed1991

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↗
PubMed1996

Intraspecific nuclear DNA variation in Drosophila.

We have summarized and analyzed all available nuclear DNA sequence polymorphism studies for three species of Drosophila, D. melanogaster (24 loci), D. simulans (12 loci), and D. pseudoobscura (5 loci). Our major findings are: (1) The average nucleotide heterozygosity ranges from about 0.4% to 2% depending upon species and function of the region, i.e., coding or noncoding. (2) Compared to D. simulans and D. pseudoobscura (which are about equally variable), D. melanogaster displays a low degree of DNA polymorphism. (3) Noncoding introns and 3' and 5' flanking DNA shows less polymorphism than silent sites within coding DNA. (4) X-linked genes are less variable than autosomal genes. (5) Transition (Ts) and transversion (Tv) polymorphisms are about equally frequent in non-coding DNA and at fourfold degenerate sites in coding DNA while Ts polymorphisms outnumber Tv polymorphisms by about 2:1 in total coding DNA. The increased Ts polymorphism in coding regions is likely due to the structure of the genetic code: silent changes are more often Ts's than are replacement substitutions. (6) The proportion of replacement polymorphisms is significantly higher in D. melanogaster than in D. simulans. (7) The level of variation in coding DNA and the adjacent noncoding DNA is significantly correlated indicating regional effects, most notably recombination. (8) Surprisingly, the level of polymorphism at silent coding sites in D. melanogaster is positively correlated with degree of codon usage bias. (9) Three proposed tests of the neutral theory of DNA polymorphisms have been performed on the data: Tajima's test, the HKA test, and the McDonald-Kreitman test. About half of the loci fail to conform to the expectations of neutral theory by one of the tests. We conclude that many variables are affecting levels of DNA polymorphism in Drosophila, from properties of nucleotides to population history and, perhaps, mating structure. No simple, all encompassing explanation satisfactorily accounts for the data.

Animals↗
PubMed1998

Pathogenicity and immunogenicity of different isolates of Teladorsagia circumcincta.

The effects on liveweight gain and development of immunity were studied in lambs trickle infected for 8 weeks with either a benzimidazole-resistant isolate (Moredun ovine resistant isolate, MORI), a multiple benzimidazole + ivermectin-resistant isolate (Moredun caprine resistant isolate, MCRI) or an unselected susceptible isolate (Moredun ovine susceptible isolate, MOSI) of Teladorsagia circumcincta. Plasma pepsinogen concentrations of infected groups were significantly elevated compared to an uninfected control group (P < 0.001) by day 14. The liveweight gains varied markedly but there were no statistical differences between the infected and uninfected control groups at any point in time during the study. Lambs infected with the MORI had significantly lower faecal consistency scores than the other challenged groups on days 7 and 14 (P < 0.05) but from day 21 onwards, faecal consistencies were similar in all of the groups. There was a notable difference in the pre-patent periods of the different isolates with the MOSI producing positive faecal egg counts (FECs) by day 14 of the study. The FECs remained reasonably low once infections had reached patency and there were no further differences between the groups. Following administration of anthelmintic to remove residual worms from the trickle infection, no differences between the infected groups in terms of worm burden or mucosal mast cell numbers were evident as a consequence of a single challenge infection. The changes in genetic code associated with enhanced resistance against anthelmintics do not appear to have resulted in any fundamental alteration of the pathogenicity and immunogenicity of these three isolates of Teladorsagia.

Animals↗
PubMedDate not supplied

Molecular evolution: first enzymes, gases as substrates and genetic templates.

A fundamental problem in biology is the self-assembly of the first cells capable of growth and division under anoxic conditions on the Earth. Evolution proceeded by self-assembling and self-replicating cells that reproduced their own genetic information and also changed their genetic code over time. Was it also possible that some of the first proteins were catalytic and used gases as substrates and also acted as genetic templates? This paper explores the possibility that primitive protein enzymes used gases as their substrates, and reverse translation may have been a feature in the self-assembly of the first cell(s).

Cells↗
PubMed1998

[Influenza vaccination].

In view of its high morbidity and substantial mortality in risk subjects, influenza has been a focus of attention for decades. The special ability of influenza viruses to change their genetic codes and hence their antigenicity--thereby constantly cancelling out our specific acquired immunity--poses and annually recurring threat of local epidemics and pandemics potentially fatal for large sections of the population. Influenza vaccination can significantly lower morbidity and mortality. It involves few side effects, is efficacious and cost effective . It is one of the most efficient primary preventive measures in all of medicine. The present state of knowledge is reviewed.

Adolescent↗
PubMed2001

Antimicrobial resistance mechanisms: what's hot and what's not in respiratory pathogens.

Community respiratory tract pathogens comprise Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and a few other select, but less frequent, species such as atypical bacteria, staphylococci, and some gram-negative organisms. In addition to an array of virulence factors, these bacteria have also developed a propensity to withstand a range of antimicrobial agents. These resistance mechanisms occur as either target site or antibiotic modifications or antibiotic transportation changes (prevention of cell entry or agent efflux). The genetic coding for these changes can be transmitted to progeny every 20 minutes or can be acquired from the normal flora via transformation. Presently, it is this acquisition of naked DNA by pneumococci that is a "hot" topic and the realization that unless antimicrobials are used more thoughtfully, then new agents can be rapidly rendered redundant. Other potential, but as yet unfounded, resistance scenarios include the acquisition of extended spectrum beta-lactamases by H. influenzae and the development of ribosomal changes to obviate the ketolides and oxazolidinones. To prevent the continued escalation of antimicrobial resistance, new approaches to antimicrobials must be implemented soon.

Drug Resistance, Microbial↗
PubMed1994

The regularity of changes of the Chou-Fasman parameters within the genetic code.

It has been shown that Chou-Fasman conformational parameters of amino acids, which reflect their ability to adopt a definite conformation within the peptide chain, change very regularly within the genetic code, arranged in the manner discussed recently by Siemion and Stefanowicz (1992a) (BioSystems 27, 77-84). Two mutually perpendicular C2 axes of pseudosymmetry appear in the center of the diagrams (between ACY and ACR threonine codons) presenting the changes of P alpha and P beta parameters. The left and right parts of diagrams superimpose on each other quite well when the symmetry operation involving a proper axis is performed. This phenomenon is due, in our opinion, to the regular arrangement of equivalent codons in the 'one-step mutation' ring formed by 64 triplets of the genetic code.

Amino Acid Sequence↗
PubMed1992

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↗
PubMed1996

Codon reassignment in Candida species: an evolutionary conundrum.

A number of Candida species translate the standard leucine CUG codon as serine rather than as leucine. Such codon reassignment in nuclear-encoded mRNAs is unusual and raises a number of important questions about the origin of the genetic code and its continuing evolution. In particular we must establish how a codon can come to be reassigned without extinction of the species and what, if any, selective pressure drives such potentially catastrophic changes. Recent studies on the structure and identity of the novel CUG-decoding tRNA(Ser) from several different Candida species have begun to shed light on possible evolutionary mechanisms which could have facilitated such changes to the genetic code. These findings are reviewed here and a possible molecular mechanism proposed for how the standard leucine CUG codon could have become reassigned as a serine codon.

Base Sequence↗
PubMed2000

Phylogenetic analysis of diatom coxI genes and implications of a fluctuating GC content on mitochondrial genetic code evolution.

In order to address the relationships among diatom groups and to investigate possible changes in their mitochondrial (mt) genetic codes, we have analyzed a 1.1-kb region of the cytochrome c oxidase subunit I (coxI) gene from eight diverse diatom species. A phylogenetic analysis of these coxI sequences including representative species of the Phaeophyta, Xanthophyta, Eustigmatophyta and Haptophyta showed that the diatoms (Bacillariophyta) formed a well-supported monophyletic group. Of the eight species investigated, four have been classified together as radial centric diatoms based on morphology. However, in our coxI tree, the two radial centrics belonging to the order Thlassiosirales (Skeletonema costatum and Thalassiosira nordenskioldii) were placed as the sister group to the multipolar centric diatoms, while the other two radial centrics (Melosira ambigua and Rhizosolenia setigera) were in another clade. Also, in two species of the Tharassiosirales we found UGA codons that occur at conserved tryptophan (Trp) sites in the coxI sequences, strongly indicating that UGA codes for Trp in these diatoms. No evidence of a deviant genetic code was detected in the other analyzed diatom species. There was no apparent relationship between the nucleotide third-position GC content of mtDNA (based on the sequenced coxI region) and the presence of a deviant genetic code.

Base Composition↗
PubMed1983

Code dependent conservation of the physico-chemical properties in amino acid substitutions.

The frequency of amino acid replacements in families of typical proteins has been elegantly analyzed by Argyle (1980) showing that the most frequent replacements involve a conservation of the amino acid chemical properties. The cyclic arrangement of the twenty amino acids resulting from the most frequent replacements has been described as an amino acid chemical ring. In this work, a novel amino acid replacement frequency ring is proposed, for which a conservation of over 90% of the most general physico-chemical properties can be deduced. The amino acid chemical similarity ring is also analyzed in terms of the genetic code base probability changes, showing that the discrepancy that exists between the standard deviation value of the amino acid replacement frequency matrix and its respective ideal value is almost equal to that deduced from the corresponding base codon replacement probability matrices. These differences are finally evaluated and discussed in terms of the restrictions imposed by the structure of the genetic code and the physico-chemical dissimilarities between some codons of amino acids which are chemically similar.

Amino Acid Sequence↗
PubMedDate not supplied

How mitochondria redefine the code.

Annotated, complete DNA sequences are available for 213 mitochondrial genomes from 132 species. These provide an extensive sample of evolutionary adjustment of codon usage and meaning spanning the history of this organelle. Because most known coding changes are mitochondrial, such data bear on the general mechanism of codon reassignment. Coding changes have been attributed variously to loss of codons due to changes in directional mutation affecting the genome GC content (Osawa and Jukes 1988), to pressure to reduce the number of mitochondrial tRNAs to minimize the genome size (Anderson and Kurland 1991), and to the existence of transitional coding mechanisms in which translation is ambiguous (Schultz and Yarus 1994a). We find that a succession of such steps explains existing reassignments well. In particular, (1) Genomic variation in the prevalence of a codon's third-position nucleotide predicts relative mitochondrial codon usage well, though GC content does not. This is because A and T, and G and C, are uncorrelated in mitochondrial genomes. (2) Codons predicted to reach zero usage (disappear) do so more often than expected by chance, and codons that do disappear are disproportionately likely to be reassigned. However, codons predicted to disappear are not significantly more likely to be reassigned. Therefore, low codon frequencies can be related to codon reassignment, but appear to be neither necessary nor sufficient for reassignment. (3) Changes in the genetic code are not more likely to accompany smaller numbers of tRNA genes and are not more frequent in smaller genomes. Thus, mitochondrial codons are not reassigned during demonstrable selection for decreased genome size. Instead, the data suggest that both codon disappearance and codon reassignment depend on at least one other event. This mitochondrial event (leading to reassignment) occurs more frequently when a codon has disappeared, and produces only a small subset of possible reassignments. We suggest that coding ambiguity, the extension of a tRNA's decoding capacity beyond its original set of codons, is the second event. Ambiguity can act alone but often acts in concert with codon disappearance, which promotes codon reassignment.

Base Composition↗
PubMed1998

Neurotrophic factors and the maldevelopmental hypothesis of schizophrenic psychoses. Review article.

The maldevelopmental model of schizophrenia postulates pathological alterations in embryonal neurogenesis as the etiopathogenetic basis of schizophrenic psychosis; the neurotrophic factor hypothesis explains these changes as the result of disturbances of processes involving the trophic factors. Neurotransmitter deficits are thereby interpreted as epiphenomena of underlying neurotrophic factor deficacy. The functional systems of the various neurotrophic factors are characterized by complex interaction mechanisms. Both primary genetic alterations, and secondary impairments, induced by exogene noxae, of the receptors and signal transducers associated with neurotrophic factors, as well as of the neurotrophic factors themselves are possible. Preliminary clinical studies indicate that schizophrenic psychoses may be associated with changes in the genetic code of certain neurotrophic factors. Various phenomena typical of the schizophrenic psychoses can be interpreted according to the neurotrophic factor hypothesis.

Animals↗
PubMed1979

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↗