Histone methylation is one of the molecular mechanisms of epigenetics in which a methyl group or more can be added to the DNA histone proteins. Histone methylation can alter gene expression and thus the overall cellular function. The transfer of the methyl group from the donor AdoMet to the lysine residue of the histone can be mediated via classical transfer or quantum tunneling. In the present study, we aim to explore the role of quantum tunneling in histone methylation compared with the classical transfer of methyl groups. Our results indicate that quantum tunneling provides a wide range of lifetimes for methylated histones between 1.56 x 10-13 s and 1.97 x 10118 s according to the energy of the methyl group and the number of transferred methyl groups. In addition, the tunneling delay time of the methyl group is within a fraction of a picosecond, which is a reasonable time and consistent with the time required for molecular transitions. Our results showed that quantum tunneling favors hypo-methylated histones because the ratio between the lifetimes of the reversed and forward reactions τ_(Q_r )/τ_(Q_f ) equals 1, while classical transfer favors hyper-methylated histones because the same ratio for the classical transfer τ_(C_r )/τ_(C_f ) can range from 4.73 x 108 to 9.6 x 104, depending on the number of transferred methyl groups. However, the ratio is between (1- 4.73 x 108) when either the classical or the quantum transfer is dominant during either the forward or reversed reactions. Moreover, temperature and enzymatic dynamics are important factors that can modulate the lifetime of methylation states.
Histone methylation is one of the molecular mechanisms of epigenetics in which a methyl group or more can be added to the DNA histone proteins. Histone methylation can alter gene expression and thus the overall cellular function. The transfer of the methyl group from the donor AdoMet to the lysine residue of the histone can be mediated via classical transfer or quantum tunneling. In the present study, we aim to explore the role of quantum tunneling in histone methylation compared with the classical transfer of methyl groups. Our results indicate that quantum tunneling provides a wide range of lifetimes for methylated histones between 1.56 x 10-13 s and 1.97 x 10118 s according to the energy of the methyl group and the number of transferred methyl groups. In addition, the tunneling delay time of the methyl group is within a fraction of a picosecond, which is a reasonable time and consistent with the time required for molecular transitions. Our results showed that quantum tunneling favors hypo-methylated histones because the ratio between the lifetimes of the reversed and forward reactions τ_(Q_r )/τ_(Q_f ) equals 1, while classical transfer favors hyper-methylated histones because the same ratio for the classical transfer τ_(C_r )/τ_(C_f ) can range from 4.73 x 108 to 9.6 x 104, depending on the number of transferred methyl groups. However, the ratio is between (1- 4.73 x 108) when either the classical or the quantum transfer is dominant during either the forward or reversed reactions. Moreover, temperature and enzymatic dynamics are important factors that can modulate the lifetime of methylation states.
A quantum mechanical model on histone modification is proposed. Along with the methyl / acetate or other groups bound to the modified residues the torsion angles of the nearby histone chain are supposed to participate in the quantum transition cooperatively. The transition rate W is calculated based on the non-radiative quantum transition theory in adiabatic approximation. By using W's the reaction equations can be written for histone modification and the histone modification level can be calculable from the equations, which is decided by not only the atomic group bound to the modified residue, but also the nearby histone chain. The theory can explain the mechanism for the correlation between a pair of chromatin markers observed in histone modification. The temperature dependence and the coherence-length dependence of histone modification are deduced. Several points for checking the proposed theory and the quantum nature of histone modification are suggested as follows: 1, The relationship between lnW and 1/T is same as usual protein folding. The non-Arhenius temperature dependence of the histone modification level is predicted. 2, The variation of histone modification level through point mutation of some residues on the chain is predicted since the mutation may change the coherence-length of the system. 3, Multi-site modification obeys the quantum superposition law and the comparison between multi-site transition and single modification transition gives an additional clue to the testing of the quantum nature of histone modification.
The influence of quantum tunnelling on double hydrogen transfers within DNA base pairs is investigated by solving the time-dependent Schrodinger equation (TDSE) for a one-dimensional double well potential, whilst accounting for environment coupling. The energies of the canonical (standard, amino-keto) and tautomeric (non-standard, imino-enol) charge-neutral forms of the adenine-thymine base pair (A-T and A*-T*, respectively) are calculated using density functional theory. These compare favourably to results in existing literature. The reaction pathway is also calculated using a transition state search to provide the barrier height and shape, and these are combined to create the potential using a polynomial fit. It is found that tunnelling is very unlikely to be a significant mechanism for the creation of adenine-thymine tautomers within DNA, with the anti-Zeno effect from environment coupling only being able to boost the tunnelling probability at any given time to ~2 x 10-9. This is barely increased when varying several parameters, such as barrier height, potential asymmetry, and mass (kinetic isotope effect). In addition, the general effect on a quantum system by its surrounding environment is explored. A novel comparison between two distinct methods of environment coupling - dissipation (via the addition of a Lindblad term to the master equation) and von Neumann measurements - is performed. This is done using a simpler model of benzoic acid dimer, where it is shown that the two methods describe the same physical process of decoherence and can be thought of as equivalent until the link between them breaks down at high temperatures and measurement frequencies.
• Published in Nature's sister journal Communications Physics, proposing an 'open quantum systems approach to proton tunnelling in DNA'. • Analysis of G-C base pairs confirmed that the proton transfer rate by tunnelling is overwhelmingly higher than classical methods even at biological temperatures and in a dissipative environment. • Demonstrated a high tautomeric occupation probability... suggesting that DNA mutation is deeply governed by quantum mechanical processes. [Quantum Biology Society] Research revealing that the fundamental cause of mutations threatening the genetic stability of DNA—the core of life preservation—is based on quantum mechanical phenomena rather than classical biochemical reactions is drawing significant attention from the academic community. A paper published in Communications Physics, a sister journal of Nature, titled "An open quantum systems approach to proton tunnelling in DNA" verified this innovative hypothesis with a sophisticated physical model. A joint research team, including Louie Slocombe and Professor Jim Al-Khalili, thoroughly analyzed the quantum mechanical processes related to proton transfer. ■ Protons Piercing Through Hydrogen Bonds, Inducing 'Point Mutations' If a proton moves out of its orbit within the hydrogen bonds of the Guanine-Cytosine (G-C) base pair connecting the DNA double helix structure, tautomerisation occurs, altering the chemical structure of the base, which can lead to a point mutation, an error in genetic information. However, exactly how this process occurs in a warm and complex biological environment has long been a matter of debate. To solve this challenge, the research team applied an open quantum system that integrated an accurate structural model of the G-C base pair with the quantum dynamics of the hydrogen bond proton and the influence of the decoherent and dissipative cellular environment. ■ Quantum Effects Surviving Even in Biological Environments... "Tens of Thousands of Times Faster Than Over-the-Barrier Hopping" The analysis results completely overturned the conventional wisdom that quantum phenomena are confined only to the microscopic world or cryogenic temperatures. The research team found that, despite biological temperatures and environmental factors, the quantum tunnelling contribution to the proton transfer rate is several orders of magnitude (tens of thousands of times) larger than the classical 'over-the-barrier hopping' method, where particles gain energy to cross the barrier. Due to the strong quantum tunnelling effect, the canonical and tautomeric forms of the G-C base pair inter-convert over timescales far shorter than biological ones and very rapidly reach thermal equilibrium. ■ The Origins of Cancer and Evolution Lie in Quantum Probabilities What is even more surprising is that the tautomeric occupation probability through tunnelling reaches a significant level of 1.73 × 10⁻⁴. This suggests that such proton transfer may well play a far more dominant and important role in DNA mutation than the academic community has hitherto thought. This study, which proves that DNA mutations—the macroscopic consequences driving the onset of genetic diseases or cancer, and further, the evolution of life—are in fact thoroughly governed by microscopic quantum tunnelling phenomena, will serve as a powerful indicator of how Quantum Biology can innovate the paradigms of medicine and genetics in the future.
• A study published in the international journal Communications Physics demonstrated the phenomenon of proton tunneling inside DNA utilizing an open quantum systems approach. • The research confirmed that protons within DNA hydrogen bonds pass through binding barriers via quantum tunnelling, going well beyond simple thermal fluctuations, and that this plays a dominant role in the conversion of base pairs into rare tautomers. • This is a groundbreaking result proving that the fundamental genetic mutation process of life is driven by microscopic quantum tunneling probabilities, revealing that tautomeric states can induce natural point mutations. [Quantum Biology Society] The DNA double helix, which contains all the genetic information of living organisms, is stably maintained by hydrogen bonds between base pairs. However, even in this robust structure, unexplained point mutations occasionally occur, becoming the seeds of evolution and disease. Recently, a study demonstrating that quantum tunnelling—a bizarre physical law of the subatomic world—is deeply involved behind this fundamental biological phenomenon was published, surprising both the biology and physics communities. The paper detailing this groundbreaking discovery, titled "An open quantum systems approach to proton tunnelling in DNA," was made freely available in Communications Physics, a sister journal to the world-renowned Nature. A research team consisting of Louie Slocombe, Marco Sacchi, and Jim Al-Khalili from the University of Surrey in the UK led this interdisciplinary study. ■ The Power of Quantum Tunneling Beyond Classical Chemistry From the perspective of general classical biochemistry, it has been assumed that for protons forming DNA hydrogen bonds to change positions, sufficient thermal fluctuation is required to overcome the binding barrier. However, the researchers discovered a surprising fact through an open quantum systems model that precisely reflects the effects of decoherence and dissipation within the cellular environment. Protons instantly change their binding positions through quantum tunneling, passing through the barrier despite a lack of energy, and the contribution of quantum tunneling to the chemical reaction rate is several orders of magnitude larger than classical over-the-barrier hopping. ■ The Beginning of Mutation: Tautomeric Conversion According to the analysis, this quantum tunneling plays a dominant role in the conversion of Guanine-Cytosine (G-C) base pairs from their canonical form into highly rare and unstable tautomeric forms. The problem arises when the DNA strands are separated by the helicase enzyme and replication occurs in this state. The research team confirmed that at biological temperatures (around 300K), the thermal equilibrium occupation probability of the tautomer reaches an astoundingly high value of 1.73 × 10⁻⁴. This is significantly higher than the previously known natural spontaneous mutation rate (about 10⁻⁸), strongly suggesting that tautomerisation via quantum tunneling is a substantial and crucial cause of point mutations. ■ Presenting a New Paradigm in Life Sciences This study is a monumental achievement proving that genetic stability and the mutation process—the most fundamental and secretive domain of life—are not accidental chemical mistakes but are directly driven by the probability of quantum tunneling, a physical law of the microscopic world. This is a powerful demonstration that overturns the conventional view of interpreting biological phenomena solely through macroscopic molecular structures and chemical bonds, showing that quantum mechanics can be the key to fully explaining genetic mutation models.
A study published on bioRxiv demonstrated that quantum tunneling plays a key role in in vitro hydrolytic enzyme reactions by analyzing kinetic isotope effects (KIE) through deuterium substitution. The involvement of the quantum tunneling effect was confirmed through temperature dependence experiments in major biochemical reactions such as SIRT3-mediated deacetylation, I-SceI-mediated DNA cleavage, and caspase-3-mediated protein cleavage. By observing that DNA homologous recombinational (HR) repair in living cells is almost completely inhibited in a deuterium environment that lowers the probability of quantum tunneling, it was demonstrated that quantum effects dominate cell survival itself. [Quantum Biology Society] Behind life phenomena lies a strange quantum world that cannot be explained by classical mechanics. A prime example is quantum tunneling, where particles pass through reaction energy barriers as if by magic. While it has been known that quantum tunneling contributes to speeding up some enzyme reactions inside proteins , there has been a lack of concrete empirical evidence as to whether this is an essential physical requirement directly linked to actual cell survival. Recently, a groundbreaking study was published showing that if the quantum tunneling effect is inhibited, the cell's life support system itself completely halts. The paper titled "Cell viability is dominated by quantum effects," published on the preprint repository bioRxiv, strongly supports this. A multi-institutional joint research team, including Takeshi Yasuda from the National Institutes for Quantum and Radiological Sciences and Technology (QST) and Kobe University in Japan, led this innovative research. ■ The Link Between Enzyme Hydrolysis and Quantum Tunneling The research team utilized deuterium, an isotope of hydrogen, to track how quantum tunneling is involved in enzymatic chemical reactions. In a heavy deuterium environment, the probability of quantum tunneling is significantly lower compared to light hydrogen, and the research team precisely measured the resulting kinetic isotope effects (KIE) and their temperature dependence. Experimental results proved that the quantum tunneling effect is deeply involved in in vitro hydrolysis reactions essential for cellular metabolism, such as SIRT3-mediated deacetylation, I-SceI-mediated DNA cleavage, and caspase-3-mediated protein cleavage, as evidenced by the disappearance of the isotope effect above specific temperatures. ■ A Halted DNA Repair System Furthermore, the research team directly investigated the impact of the quantum characteristics of these enzyme reactions on living cells. When human cells were exposed to a deuterium-substituted (D₂O) medium environment that artificially lowered the probability of quantum tunneling, it was observed that DNA homologous recombinational (HR) repair, one of the core survival mechanisms of cells, was almost completely inhibited. This means that the most important biochemical repair process protecting and maintaining the genetic information of organisms undergoes a chain reaction of several enzymes and cannot function normally without quantum tunneling phenomena. ■ Quantum Effects Dominating Cell Viability This study empirically demonstrates that core biochemical reactions in living organisms do not simply rely on thermodynamic energy but are fundamentally indebted to quantum mechanical tunneling phenomena. The discovery that numerous hydrolysis and repair reactions performed by enzymes within cells are ultimately strictly dominated by quantum effects serves as crucial evidence that rewrites life phenomena from a purely quantum physics perspective. https://www.biorxiv.org/content/10.1101/2023.07.18.549596v1
This study investigates the impact of temperature-induced quantum proton tunneling probability on DNA amplification during polymerase chain reactions (PCR). Using a simulation model based on a Gaussian wavefunction and finite-difference time-domain method, quantum tunneling of protons across square potential barriers is examined. The results unveil consistent probability distributions for quantum tunneling across various PCR temperatures, with distinct oscillation patterns emerging post-barrier crossing. Acknowledging limitations in initial conditions due to temperature-dependent proton energy, the study highlights the need for refined models and experimental validation. These findings accentuate the potential interplay between quantum mechanics and biological systems, prompting further research to understand quantum tunnelling’s comprehensive effect on genetic variations and molecular processes.