Dataset Information

Non-poissonian Distribution of Point Mutations in DNA.

ABSTRACT: In general, for chemical reactions occurring in systems, where fluctuations are not negligibly small, it is necessary to introduce a master equation for distribution of probability of fluctuations. It has been established that the monomolecular reactions of a type as A ? X are described by the master equation, which leads to a Poisson distribution with the variance equal to the average value N 0. However, the consideration of the Löwdin mechanism as autocatalytic non-linear chemical reactions such as A + X ? 2X and the corresponding master equation lead to a non-Poissonian probability distribution of fluctuations. In the presented work, first-order autocatalysis has been applied to the Löwdin's mechanism of spontaneous mutations in DNA. Describing double proton transfers between complimentary nucleotide bases along the chain by first-order autocatalytic reactions, the corresponding master equation for protons in tautomeric states becomes non-linear, and at non-equilibrium conditions this leads to the non-Poissonian distribution of spontaneous mutations in DNA. It is also suggested that the accumulation of large fluctuations of successive cooperative concerted protons along the chain may produce higher non-linearities which could have a significant impact on some biochemical processes, occurring in DNA.

SUBMITTER: Turaeva N

PROVIDER: S-EPMC7005246 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Non-poissonian Distribution of Point Mutations in DNA.

Turaeva Nigora N Oksengendler Boris L BL

Frontiers in chemistry 20200131

In general, for chemical reactions occurring in systems, where fluctuations are not negligibly small, it is necessary to introduce a master equation for distribution of probability of fluctuations. It has been established that the monomolecular reactions of a type as A ↔ X are described by the master equation, which leads to a Poisson distribution with the variance equal to the average value N 0. However, the consideration of the Löwdin mechanism as autocatalytic ...[more]

PMID: 32083056

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Project description:BACKGROUND: We have developed an oligonucleotide microarray (genosensor) utilizing a double tandem hybridization technique to search for 9 point mutations located in the most frequently altered codons of the TP53 gene. Isolated and multiplexed PCR products, 108 and 92 bp long, from exons 7 and 8, respectively, were obtained from 24 different samples. Single-stranded target DNA was then prepared from isolated or multiplexed PCR products, through cyclic DNA synthesis. Independent ssDNA's were annealed with the corresponding pairs of labeled stacking oligonucleotides to create partially duplex DNA having a 7-nt gap, which contains the sequence that will be interrogated by the capture probes forming double tandem hybridization. In the case of multiplexed ssPCR products, only two stacking oligonucleotides were added per target, therefore the gap for the PCR products having two consecutive codons to be interrogated in exon 7 was 12 nt long, so only single tandem hybridization was produced with these respective probes. RESULTS: 18 codon substitutions were found by DNA sequencing. In 13 of them a perfect correlation with the pattern of hybridization was seen (In 5 no signal was seen with the wt probe while a new signal was seen with the appropriate mutant probe, and in 8 more, as expected, no signal was seen with any probe due to the absence of the corresponding probe in the array). In 3 other cases a mutation was falsely suggested by the combination of the absence of the wild type signal along with a false signal in the other probe. In the other 2 cases the presence of the mutation was not detected due to the production of a false hybridization signal with the wild type probe. In both cases (false mutation or no mutation detected) relatively stable mismatched target/probe duplexes should be formed. These problems could be avoided by the addition of probes to improve the performance of the array. CONCLUSION: Our results demonstrate that a simple TP53 microarray employing short (7-mer) probes, used in combination with single or double tandem hybridization approach and a simple or multiplex target preparation method, can identify common TP53 missense mutations from a variety of DNA sources with good specificity.

Dataset Information

Non-poissonian Distribution of Point Mutations in DNA.

Publications

Non-poissonian Distribution of Point Mutations in DNA.

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