The molecules of life, DNA, replicate with astounding precision, yet this
process is not immune to mistakes and can lead to mutations. Using
sophisticated computer modeling, a team of physicists and chemists at the
University of Surrey have shown that such errors in copying can arise due to
the strange rules of the quantum world.
The two strands of the famous DNA double helix are linked together by
subatomic particles called protons—the nuclei of atoms of hydrogen—which
provide the glue that bonds molecules called bases together. These so-called
hydrogen bonds are like the rungs of a twisted ladder that makes up the
double helix structure discovered in 1952 by James Watson and Francis Crick
based on the work of Rosalind Franklin and Maurice Wilkins.
Normally, these DNA bases (called A, C, T and G) follow strict rules on how
they bond together: A always bonds to T and C always to G. This strict
pairing is determined by the molecules' shape, fitting them together like
pieces in a jigsaw, but if the nature of the hydrogen bonds changes
slightly, this can cause the pairing rule to break down, leading to the
wrong bases being linked and hence a mutation. Although predicted by Crick
and Watson, it is only now that sophisticated computational modeling has
been able to quantify the process accurately.
The team, part of Surrey's research program in the exciting new field of
quantum biology, have shown that this modification in the bonds between the
DNA strands is far more prevalent than has hitherto been thought. The
protons can easily jump from their usual site on one side of an energy
barrier to land on the other side. If this happens just before the two
strands are unzipped in the first step of the copying process, then the
error can pass through the replication machinery in the cell, leading to
what is called a DNA mismatch and, potentially, a mutation.
In a paper published this week in the journal Communications Physics, the
Surrey team based in the Leverhulme Quantum Biology Doctoral Training Center
used an approach called open quantum systems to determine the physical
mechanisms that might cause the protons to jump across between the DNA
strands. But, most intriguingly, it is thanks to a well-known yet almost
magical quantum mechanism called tunneling—akin to a phantom passing through
a solid wall—that they manage to get across.
It had previously been thought that such quantum behavior could not occur
inside a living cell's warm, wet and complex environment. However, the
Austrian physicist Erwin Schrödinger had suggested in his 1944 book "What is
Life?" that quantum mechanics can play a role in living systems since they
behave rather differently from inanimate matter. This latest work seems to
confirm Schrödinger's theory.
In their study, the authors determine that the local cellular environment
causes the protons, which behave like spread out waves, to be thermally
activated and encouraged through the energy barrier. In fact, the protons
are found to be continuously and very rapidly tunneling back and forth
between the two strands. Then, when the DNA is cleaved into its separate
strands, some of the protons are caught on the wrong side, leading to an
error.
Dr. Louie Slocombe, who performed these calculations during his Ph.D.,
explains that: "The protons in the DNA can tunnel along the hydrogen bonds
in DNA and modify the bases which encode the genetic information. The
modified bases are called "tautomers" and can survive the DNA cleavage and
replication processes, causing "transcription errors" or mutations."
Dr. Slocombe's work at the Surrey's Leverhulme Quantum Biology Doctoral
Training Center was supervised by Prof Jim Al-Khalili (Physics, Surrey) and
Dr. Marco Sacchi (Chemistry, Surrey).
Prof Al-Khalili comments: "Watson and Crick speculated about the existence
and importance of quantum mechanical effects in DNA well over 50 years ago,
however, the mechanism has been largely overlooked."
Dr. Sacchi continues: "Biologists would typically expect tunneling to play a
significant role only at low temperatures and in relatively simple systems.
Therefore, they tended to discount quantum effects in DNA. With our study,
we believe we have proved that these assumptions do not hold."
Reference:
An open quantum systems approach to proton tunnelling in DNA, Communications
Physics (2022).
DOI: 10.1038/s42005-022-00881-8 ,