Genetic code and optimal resistance to the effects of mutations

This paper deals with the notion of resistance of the genetic code to the effects of mutations. We measure the resistance of a group of t codons as the number of pairs of those which differ from each other in only one of their three bases. We find for each value of t the maximum possible value of the resistance and we describe some groups of codons giving this value. Important examples of such configurations are found in the genetic code, among these are the groups of synonymous codons, as observed elsewhere, and the cluster of codons which have an hydrophobic amino acid for translation.     

Genetic mapping of cadmium resistance mutations inBacillus subtilis

Bacillus subtilis, which accumulates cadnium via the manganese transport system, may acquire cadmium resistance by chromosomal mutations that reduce Cd²⁺ uptake without affecting Mn²⁺ transport. A cadmium resistance mutation,cdr-1, maps at about 40° on theB. subtilis chromosome. The deduced map order wasarol-narB-mtlB-cdr-dal-purB. Thecdr mutations in four other, independently isolated Cd²⁺-resistant mutants demonstrating reduced Cd²⁺ uptake also mapped betweenaroI anddal.     

The logic of the genetic code: Synonyms and optimality against effects of mutations

The groups of codons which correspond to the same amino-acid in the genetic code (synonyms) are compared to theoretical codes constructed so as to resist best to the effects of mutations. The analysis shows that the genetic code presents synonymy structures which are optimized against translation errors.     

Genetic study of plasmid-associated high-frequency mutations to streptomycin resistance in Escherichia coli]

Escherichia coli CTR1(RT1)RHfm1) carrying two H-factors and having unusually high frequency of mutation to high level streptomycin resistance is studied. The high frequency of mutation (about 10(-6) to streptomycin resistance is connected with the presence of R factor RHfm1, controlling the resistance to chloramphenicol and low level streptomacin resistance, but not with RT1, controlling the resistance to tetracycline. Spontaneous or ethidium bromide-induced loss of RHfm1 is accompanied by a decrease of the mutation frequency to 10(-9). RHfm1 is efficiently transmissible to other strains at 28 degrees C. The acquisition of RHfm1 by strains of E. coli K-12 ans S. typhimurium LT2 was followed by a 1000--10000-fold increase of the frequejcy of mutation to streptomycin resistance. Some streptomycin resistant mutants were isolated, and chromosome location of the mutations was demonstrated. The streptomycin resistant mutants were unable to transmit high level of resistance to streptomycin with R factor, but only low level one. The loss of RHfm1 by streptomycin resistant mutants was accompanied by the return to the streptomycin sensitivity of the initial R- strans (E. coli K-12 mutants) or by a decrease of the streptomycin resistance to the level, only 2-fold higher than that of R- wild type (E. coli CTR1 mutant). Thus, the mutantions had practically no effect on streptomycin resistance of R- strains, but could lead to high resistance phenotypes in the presence of RHfm1. The mutant loci in all three studied strains were found to be closely linked to the locus "fus" on the genetic map of E. coli.     

Neutral mutations and interference-stability of the genetic code

The fundamental suggestions of the neutral theory of evolution are discussed. It is shown that the safety of the genetic code is expressed also in the thermostability of proteins, i.e. in their conformational mobility. There is no contradiction between the mutational changes of the protein thermostability and the neutral theory.     

Genetic evaluation of relationship between mutations in rpoB and resistance of Mycobacterium tuberculosis to rifampin

Background  

Rifampin is a first line antituberculosis drug active against bacilli in logarithmic and stationary phase, which interferes with RNA synthesis by binding to bacterial RNA polymerase. Tubercle bacilli achieve resistance to rifampin by accumulation of mutations in a short-81 bp region of the rpoB gene. Among many mutations identified in the rpoB gene, few were verified by molecular genetic methods as responsible for resistance to rifampin (RMP).     

Genetic and biochemical characterization of kirromycin resistance mutations in Bacillus subtilis.

Spontaneous mutations causing resistance to the EF-Tu-specific antibiotic kirromycin have been isolated and mapped in Bacillus subtilis. Three-factor transductional and transformational crosses have placed the kir locus proximal to ery-1 and distal to strA (rpsL) and several mutations affecting elongation factors EF-G and EF-Tu, in the order: cysA strA [fus-1/ts-6(EF-G)] [ts-5(EF-Tu)] kir ery-1 spcA. Purified EF-Tu from mutant strains is more resistant to kirromycin as measured by in vitro protein synthesis and also shows a more acidic isoelectric point than wild-type EF-Tu. This indicates that the kir locus is the genetic determinant (tuf) for EF-Tu and that there is a single active gene for this enzyme in B. subtilis.     

Early fixation of an optimal genetic code

The evolutionary forces that produced the canonical genetic code before the last universal ancestor remain obscure. One hypothesis is that the arrangement of amino acid/codon assignments results from selection to minimize the effects of errors (e.g., mistranslation and mutation) on resulting proteins. If amino acid similarity is measured as polarity, the canonical code does indeed outperform most theoretical alternatives. However, this finding does not hold for other amino acid properties, ignores plausible restrictions on possible code structure, and does not address the naturally occurring nonstandard genetic codes. Finally, other analyses have shown that significantly better code structures are possible. Here, we show that if theoretically possible code structures are limited to reflect plausible biological constraints, and amino acid similarity is quantified using empirical data of substitution frequencies, the canonical code is at or very close to a global optimum for error minimization across plausible parameter space. This result is robust to variation in the methods and assumptions of the analysis. Although significantly better codes do exist under some assumptions, they are extremely rare and thus consistent with reports of an adaptive code: previous analyses which suggest otherwise derive from a misleading metric. However, all extant, naturally occurring, secondarily derived, nonstandard genetic codes do appear less adaptive. The arrangement of amino acid assignments to the codons of the standard genetic code appears to be a direct product of natural selection for a system that minimizes the phenotypic impact of genetic error. Potential criticisms of previous analyses appear to be without substance. That known variants of the standard genetic code appear less adaptive suggests that different evolutionary factors predominated before and after fixation of the canonical code. While the evidence for an adaptive code is clear, the process by which the code achieved this optimization requires further attention.     

Stability of the genetic code and optimal parameters of amino acids

The standard genetic code is known to be much more efficient in minimizing adverse effects of misreading errors and one-point mutations in comparison with a random code having the same structure, i.e. the same number of codons coding for each particular amino acid. We study the inverse problem, how the code structure affects the optimal physico-chemical parameters of amino acids ensuring the highest stability of the genetic code. It is shown that the choice of two or more amino acids with given properties determines unambiguously all the others. In this sense the code structure determines strictly the optimal parameters of amino acids or the corresponding scales may be derived directly from the genetic code. In the code with the structure of the standard genetic code the resulting values for hydrophobicity obtained in the scheme “leave one out” and in the scheme with fixed maximum and minimum parameters correlate significantly with the natural scale. The comparison of the optimal and natural parameters allows assessing relative impact of physico-chemical and error-minimization factors during evolution of the genetic code. As the resulting optimal scale depends on the choice of amino acids with given parameters, the technique can also be applied to testing various scenarios of the code evolution with increasing number of codified amino acids. Our results indicate the co-evolution of the genetic code and physico-chemical properties of recruited amino acids.     

Genetic analysis and screening of pyrethroid resistance mutations in Varroa destructor populations from Turkey

Experimental and Applied Acarology - Varroa destructor is the most common ectoparasite of the Western honey bee (Apis mellifera L.) worldwide and poses a serious threat to bee health. Synthetic...     

Genetic diversity and resistance to marine pollution

We tested in the laboratory three pairs of species belonging to three genera and families of marine gastropods, Monodonta turbinata, M. turbiformis (Trochidae), Littorina punctata, L. neritoides (Littorinidae), Cerithium scabridum, C. rupestre (Cerithiidae), for resistance to diverse inorganic (heavy metals and NaC1) and organic (detergents and crude oil) pollutants. Each pair consisted of one narrow-niche species with low genetic diversity and one broad-niche species with higher genetic diversity. Evidence is presented that in all three cases the species with a higher level of genetic diversity was more resistant to all pollutants than its counterpart. These results suggest that fitness is positively correlated with heterozygosity and support the niche-width-variation hypothesis in regard to pollutants. The results also have practical implications for the identification of optimum marine species as genetic monitors of pollution.     

Genetic code and phylogenetic origin of oomycetous mitochondria

Summary We sequenced the 3-terminal part of the COX3 gene encoding cytochrome c oxidase subunit 3 from mitochondria of Phytophthora parasitica (phylum Oomycota, kingdom Protoctista). Comparison of the sequence with known COX3 genes revealed that UGG is used as a tryptophan codon in contrast to UGA in the mitochondrial codes of most organisms other than green plants. A very high AT mutation pressure operates on the mitochondrial genome of Phytophthora, as revealed by codon usage and by A + T content of noncoding regions, which seems paradoxical because AT pressure causes tryptophan codon reassignment from UGG to UGA in mitochondria of most species. The genetic code and other data suggest that mitochondria of Oomycota share a direct common ancestor with mitochondria of plants and that mitochondria of the ancestor of Planta and Oomycota were acquired in a second endosymbiotic event, which occurred later than the acquisition of mitochondria by other eukaryotes.Offprint requests to: P. Karlovsky     

DNA topoisomerase II mutations and resistance to anti-tumor drugs

Mutations in DNA topoisomerase II are often correlated with drug-resistance in tumor cell lines. Studies of topoisomerase II-mediated drug-resistance in various model systems, as well as the sequencing of such mutations from drug-resistant tumors, have shed light on the functional domains of topoisomerase II, on how it interacts with inhibitors, and on the different mechanisms by which cells avoid the toxic effects of many clinically important anti-tumor drugs.     

Genetic analysis of resistance to swede mildew

The incidence of swede mildew (Erysiphe cruciferarum) was analysed on three occasions in five swede varieties Crifel, Doon Major, Harvester, Ne Plus Ultra and Ruta Øtofte and their F₁ hybrids. Overall levels of infection were greater in Ne Plus Ultra and Harvester and least in Ruta Øtofte. Genetic analysis by the diallel method showed that initially resistance was recessive with Ruta Øtofte possessing most recessive genes but results from the final analysis showed partial dominance, with Ne Plus Ultra having most recessive and Harvester most dominant genes. The changing pattern of inheritance with time was due to variation in the rates of increase in disease incidence and diallel analyses of these rates, calculated by regression analyses over five observations, showed in almost entirely additive control. Although no variety was immune it was considered that except on soils of high pH or in the event of a marked change in the genetic composition of the pathogen the level of resistance in Ruta Øtofte was satisfactory.