Science

The quantum effect can be the cause of spontaneous DNA mutations.

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The complexity of any life form on Earth is based largely on the accuracy of the genetic information compressed into each cell of which it is composed. However, it happens that this accuracy is subject to errors that can lead to DNA incompatibilities or mutations. A very slight change in the nature of the hydrogen bonds between base pairs is enough for a mismatch to occur. The quantum tunneling effect will be particularly involved in these “accidents” of coupling, which occur more frequently than we thought so far. Computer simulations from the University of Surrey have demonstrated for the first time the involvement of quantum mechanics in DNA replication, a phenomenon already predicted in the 1950s by geneticists James Watson and Francis Crick.

James Watson and Francis Crick were inspired by the work of Rosalind Franklin and Maurice Wilkins to discover the DNA double helix structure in 1952. The two strands that make up this highly complex helical structure are held together by protons delivered by hydrogen atoms. These atoms make up the steps by which molecular bases bind to each other according to a strict universal rule: adenine (A) always binds to thymine (T), and cytosine (C) always binds to guanine (G). This connection is determined by the shape of each base, so that hydrogen bonds hold them together like puzzle pieces.

A defect in the hydrogen bonds can upset this strict balance, causing the assembly of incorrect base pairs, and thus lead to what is called DNA incompatibility. Natural mutations are completely random and unpredictable, but their frequency can be increased by endogenous or exogenous factors (genetic inheritance from parents, chemical or physical agents, etc.). Today, mutations can also be artificially induced using gene editing techniques such as CRISPR-Cas9.

The new study, published in the journal Nature Communications Physics, focuses on natural mutations by examining the possibility of a mismatch between the bases guanine (G) and cytosine (C). According to the authors, the transfer of protons through hydrogen bonds in the wrong place can threaten the stability of the entire structure of the DNA strand. “Watson and Crick have been speculating about the existence and importance of quantum effects in DNA over 50 years ago. However, this mechanism is largely overlooked,” Jim Al-Khalili, a physicist at the University of Surrey and lead researcher, said in a statement.

The research team then used a so-called “open quantum system” approach to identify and model the physical mechanisms that can make protons “jump” between DNA strands.

Protons in the wrong place

Mismatches between DNA strands are more common than previously thought, according to the Surrey research team. If we really thought that these were very rare biological accidents, then protons can really easily “jump” from their usual place to be on the other side of the energy barrier. If this “jump” occurs just before the unpacking of the two strands in the normal first step of copying, the error can propagate through most of the cell’s replication mechanisms, resulting in a DNA mismatch and possibly mutation.

This displacement of protons can be particularly frequent because at the base, the local environment (within the cell) causes protons to be thermally activated and stimulated across the energy barrier. Moreover, these protons will carry out a very fast and continuous movement back and forth between the two strands. And when two strands split into separate strands, some of the protons end up on the wrong side, leading to replication errors.

Overcoming this energy barrier is possible thanks to the quantum tunneling effect, a mechanism involving subatomic particles (protons, electrons, neutrons, etc.) that allows them to overcome a barrier that is considered insurmountable. To get a clearer idea: it is as if a small object locked in a box could come out of it without opening it or deforming it, or as if it were leaning against a wall and could cross it without damaging it.

“DNA protons can tunnel along DNA hydrogen bonds and change the bases that encode genetic information,” says Louis Slocombe, lead author of the study and research fellow at the Center for Doctoral Studies in Quantum Biology in Surrey. According to the expert, these modified bases, known as tautomers (a pair of interconvertible isomers in which a hydrogen atom migrates), can survive DNA cleavage and replication, leading to transcription errors or mutations.

In addition, until now it was also believed that the effect of quantum tunneling cannot manifest itself in the warm, humid and complex environment of a living cell. In particular, this has always been observed in low-temperature environments, so, according to the authors of the study, quantum effects in DNA have long been neglected.

Nature Communications Physics.

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