Non-poissonian Distribution of Point Mutations in DNA.

Nigora Turaeva,Boris L Oksengendler

doi:10.3389/fchem.2020.00038

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 N0. 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.

Highlights

The role of mutations in DNA is crucial for human aging, metabolic and degenerative disorders and cancer, as well as for biological evolution of living systems (Löwdin, 1966; Friedberg et al, 2006)
The point mutations caused by the substitution of one nucleotide base for another may occur during DNA replication by DNA polymerases, the performance of which is very important for genome integrity and transmission of genetic information in all living organisms
The autocatalytic reaction of first order is applied to the process of double proton transfer in DNA, which gives a non-Poissonian distribution of tautomeric states of hydrogens along the chain which as a result of replication leads to spontaneous mutations

Summary

INTRODUCTION

The role of mutations in DNA is crucial for human aging, metabolic and degenerative disorders and cancer, as well as for biological evolution of living systems (Löwdin, 1966; Friedberg et al, 2006). The autocatalytic reaction of first order is applied to the process of double proton transfer in DNA, which gives a non-Poissonian distribution of tautomeric states of hydrogens along the chain which as a result of replication leads to spontaneous mutations. We suppose that the nonPoissonian character of the distribution function of tautomeric forms of nucleotide bases can be counted toward the Löwdin’s mechanism of origin of spontaneous mutations formation, since the intramolecular single proton transfer in DNA bases describing by the monomolecular reactions of a type as A ⇐⇒ X is described by the master equation, leading to the Poissonian distribution, where the variance is equal to the average value N0

STOCHASTIC MODEL OF SPONTANEOUS MUTATION FORMATION

CONCLUSION

AUTHOR CONTRIBUTIONS