Quantum effects help make DNA unstable


Quantum effects play a hitherto unexpected role in creating instabilities in DNA – the so-called “molecule of life” that provides instructions for cellular processes in all living organisms. This conclusion, based on work by researchers at the University of Surrey in the UK, goes against long-held beliefs that quantum behaviour is not relevant in the wet, warm environment of cells, and could have far-reaching consequences for models of genetic mutation.


The two strands of DNA’s famous double helix are linked together by bonds that form between hydrogen atoms (protons) in the four bases – guanine (G), cytosine (C), adenine (A) and thymine (T) – that make up each strand. Normally, A always bonds to T and C always bonds to G. However, if the shape of the bonding surface between the strands changes ever so slightly, the wrong bases can become linked, forming a so-called tautomeric form of DNA that can lead to stable genetic mutations or even cancer.



This effect was predicted back in 1952, when James Watson and Francis Crick drew on work by Rosalind Franklin and Maurice Wilkins to uncover DNA’s helical structure. However, it is only now that this DNA bond modification process has been accurately quantified, and its quantum element understood.


In their work, Louie Slocombe, Marco Sacchi, Jim Al-Khalili and colleagues used sophisticated computer models to show that DNA bond modification stems from the protons’ ability to transfer along the hydrogen bonds that form between the G-C bases. As the protons hop from one side of the DNA strand to the other, a mismatch occurs if one of these hops happens just before the DNA strand cleaves, or “unzips”, as part of the process it undergoes to copy itself.


To pin down what makes protons hop along DNA strands, the researchers used an open quantum systems approach. They discovered that rather than hopping along the strands, the protons are in fact quantum tunnelling through them. They also found that the tunnelling rate is so fast that the system quickly reaches thermal equilibrium, meaning that the population of tautomers remains constant over biological timescales.


Until now, it was thought that any such quantum behaviour should wash out quickly in the noisy conditions that prevail inside cells, and thus would not play any physiological role. However, Slocombe explains that the DNA system is so sensitive to the hydrogen bond arrangement that quantum effects do matter. Indeed, even the tiny rearrangement of a couple of hydrogen atoms can affect how DNA replicates on the macroscopic scale.


“The topic is exciting to study since it involves the combination of techniques and ideas from different realms of science,” Slocombe tells Physics World. “Typically, these are not congruent and we require them to be so to model the system accurately. We require knowledge of both chemistry and physics to model the systems and in addition we need to know about biology, how DNA replicates and the implications for when it mismatches.”



The researchers, who report their work in Nature Communications, express hope that their study “is the first of many” on this topic. “What most interests us,” Slocombe adds, “is what happens at the exact moment of the DNA cleaving and how the timescale of this interaction interplays with the fast timescale of the hydrogen transfer.”


Other questions include whether using ATGC bases rather than alternative forms of DNA confers some evolutionary benefit, since the former are relatively unstable. Another is whether this instability leads to mutation, thus driving the process of evolution. “It would be interesting to understand if there are any DNA repair pathways specifically designed to catch these types of errors,” Slocombe concludes.


Nature Communications


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