The linear mRNA molecule is fed into a cleft within the ribosome which, acting like a barcode reader, reads the mRNA code, a codon at a time. The ribosome also has a docking station for amino acids. The ribosomes are, however, unable to identify or incorporate naked amino acids. Instead, each amino acid has to be tagged with yet another type of RNA molecule called transfer RNA or simply tRNA. Each tRNA molecule carries a three base anticodon sequence that acts as a complementary barcode to identify the amino acid it carries. All the ribosome has to do is to pair up the two barcodes – the codon on mRNA with the anticodon on tRNA – and thereby insert the correct amino acid. The mRNA molecule is fed into the ribosome, a codon at a time, and at each step, the appropriate amino acid is clipped off the tRNA molecule and attached to the growing amino acid chain.
WHEN DNA DOESN’T WORK
The job of the DNA replication machinery is to make a perfect copy of the parental DNA strand. However, no copying is perfect – think how a photocopy of an image degrades as it is repeatedly copied in a photocopying machine. The DNA copying machinery of living cells is capable of a much higher degree of fidelity than a photocopying machine, but occasionally it does insert the wrong base. These errors are mutations that may or may not lead to changes in the amino acid sequence of proteins. Mostly the changes are of little or no consequence. Occasionally, if a mutation interferes with the function of an essential protein, it can be severely harmful, even lethal. The human genetic disease thalassemia is caused mainly by a mutation that changes a single amino acid in one of the globin proteins of blood haemoglobin. Even more rarely, mutations may provide some advantage to their host. Natural selection tends to favour organisms carrying advantageous mutations that allow them to produce more offspring. Over millions of years, organisms will evolve by selection of mutant offspring which are fitter than their parents. Mutations are therefore the elusive source of the variation that Darwin needed to complete his theory of evolution. They provide the raw material for all evolutionary change.
But where do these mutations come from? They are mostly generated during DNA replication. The enzyme that constructs new DNA strands is called DNA polymerase. Its basic activity is to string together units of nucleotides (the units of DNA that carry the bases) to make new DNA strands. However, the enzyme doesn’t work unless it has a template on which to build the new strand. The old DNA strands are first unwound to allow DNA polymerase to slide along each strand (it forms a kind of doughnut structure around the DNA) to make the new strand. But occasionally (roughly one in every ten thousand bases) DNA polymerase makes a mistake and inserts the wrong base. The enzyme has several possible excuses for its errors. Radiation and some hazardous chemicals can cause mutations and do so by promoting errors during the DNA replication process. However, one source of replication error is unavoidable because it is due to the intrinsic quantum nature of the DNA code.
In What is Life? Erwin Schrödinger proposed that genes were aperiodic crystals (crystals lacking a periodic structure) and that quantum fluctuations may be a source of mutations. However, as he went along with the prevailing view that genes were made of protein, this suggestion was generally ignored when the true nature of the genetic code became known. The Swedish geneticist Per-Olov Löwdin from the University of Uppsala revived interest in the quantum nature of the genetic code by pointing out that it could be viewed as a linear array of protons. As described above, the coding properties of DNA are due to the hydrogen bonding between protons and electrons in the DNA bases: the position of these particles determines which hydrogen bonds can form and thereby the base-pairing underlying the genetic code. Protons and electrons are fundamental particles and their position is subject to quantum mechanics. The genetic code thus becomes a quantum code.
One of the peculiar features of quantum mechanics is that in most circumstances we cannot know exactly where a particle is: its position is uncertain (an aspect of Heisenberg’s famous uncertainty principle that will be examined in more detail later). This uncertainty is the basis for a phenomenon called quantum tunnelling, whereby protons are said to tunnel from one position to another. In fact quantum particles don’t really tunnel anywhere. It is just that the inevitable (Heisenberg) uncertainty in their position means that they materialize in places you wouldn’t normally expect them.
The coding protons in DNA can (and must) quantum tunnel within the DNA molecule. This leads to tautomeric structures for DNA bases, with coding protons tunnelling from one atom to another to form modified chemical structures. Tautomeric forms of DNA bases can pair with the incorrect base: A can pair with G and T with C (rather than A with T and C with G). Watson and Crick proposed that if, during DNA replication, either the template DNA base or the incoming base is in the tautomeric form, then the wrong base may be inserted into the new strand, resulting in a mutation. Tautomeric forms of DNA bases account for about 0.01 per cent of all natural DNA bases, so incorporation of incorrect bases, due to tautomerization, is likely to be relatively common. However, our DNA replication machinery has proofreading enzymes able to recognize incorrectly inserted bases and clip them out of the growing strand. The inclusion of proof-reading into the system vastly reduces the error rate to only about one wrong base for every billion correct bases. Those errors that escape the correction machinery are the source of naturally occurring mutations; and their source is quantum-mechanical.
Watson and Crick’s structure was therefore the culmination of centuries of biological progress. The great mysteries were laid bare: how biological information is encoded, how it is inherited and how it is changed. But it also pointed in quite a surprising direction, towards the involvement of that other great triumph of twentieth century science – quantum mechanics – in the fundamental basis of life and the driving force of evolution.
We all need to place our lives in some kind of historical context, to know where we come from. Ancestor worship is one of the most ancient forms of religion and the same craving finds a modern expression in the current popularity of genealogy. A relative of mine, John McFadden, recently traced our family back to one Cornelius McFadden. Cornelius owes his fame to being caught (probably around 1760) stealing a sheep on the island of Arranmore1. Sheep stealers were hanged in eighteenth-century Ireland but the authorities could however show some mercy, since the sentence could be commuted for men with families. Fortunately for Cornelius, his wife Nancy was heavily pregnant so my great-great-great grandfather suffered the lesser punishment of having his ears cut off. His wounds bound, he and his young wife were placed on a raft and pushed out to sea on the ebb tide, with only a single oar. The pair rowed along the coast, finally beaching on the island of Innishirther – a rather bleak and inhospitable place, but uninhabited. They settled there and thrived, raising eleven children. Their descendants migrated to the mainland, giving rise to a long line of McFaddens, including eventually me. The punishment suffered by Cornelius is remembered in a Gaelic phrase, ‘Thug said Oidhe Concubhair air’ (roughly translated, the justice of Cornelius) that commemorates their cruel punishment.
The tale of Nancy and Cornelius gives me some connection with the past but a few hundred years are very shallow roots in a history of life that stretches back billions of years. To find more – truly ancient – roots we must dig deeper into the past.
THE HOOF-PRINT OF EVOLUTION
The standard textbook illustration of evolution is the development of the modern horse. Darwin’s friend and colleague Thomas Huxley worked out its sequence from more than two hundred species of fossil horses from Europe and America, using it to champion Darwin’s theory. Horses are members of the family perissodactyles (animals with odd-numbered toes) that also includes rhinos and tapirs. The first perissodactyles were dog-like browsing animals weighing only about twenty kilos that