A major feature of the double helix is that wherever a base occurs on one strand of the DNA, a complementary base is found on the opposite strand: A is paired with T and G is paired with C. The pairs of complementary bases are held together by a hydrogen bond, a type of chemical bond. Chapter Five will look at chemical bonds in more detail, but a hydrogen bond is held together by the electromagnetic force existing between a positively charged proton on one base and the negatively charged electrons on its complementary base.
The information held in the DNA double helix is therefore redundant. The same information is held in two different forms: the coding strand (the strand that codes directly for proteins) and its complement. If one strand is removed, it can be used as a template to direct the synthesis of its complementary strand. This is exactly what happens when a cell replicates its DNA. The strands are pulled apart and each is used as a template to synthesize its complement. The enzymes involved in DNA replication examine the sequence of the single-stranded template and insert only the complementary base into the newly synthesized strand (in fact, fortunately for evolution, the copying isn’t quite perfect – see below). After each strand has been copied, the pair of old and new strands form a duplex DNA molecule again. From a single parental DNA duplex, a pair of daughter duplexes is formed. One of the DNA duplex pair goes into one of the daughter cells and the other duplex goes into the other – biological information is copied. This simple mechanism underlies the replication of all living cells.
HOW DNA TELLS THE CELL WHAT TO DO
DNA encodes proteins but doesn’t make them. That job is performed by structures inside cells called ribosomes which stitch together single amino acid units into strings which are called peptides if short, proteins if they are long. Left to their own devices, ribosomes might randomly string together amino acids, making totally random proteins. Ribosomes could make a staggering variety of proteins if allowed to function in this manner. Consider a relatively small protein, say only one hundred amino acids long. For each of the hundred positions in the protein there are twenty possible amino acids that could be inserted. There are therefore 20100 different ways of putting such a protein together. 20100 is an immense number. It means the product of 20 x 20 x 20 x 20 x 20 x 20 x … 100 times. For convenience, big numbers like this are usually expressed as a power of 10, so that they can easily be compared. In this system, 20100 can also be written as 10130. For comparison, the number of electrons in the universe is a much smaller number, about 1080, so there are not even enough electrons in the entire universe to count the number of possible 100 amino acid proteins! The ribosome’s task is to make only a very tiny fraction of these possible proteins – the proteins the cell needs.
The problem is similar to house-building. The number of possible ways of putting several thousand bricks together is again a staggeringly large number and only a tiny fraction would amount to a functional house. The builder must select from the vast number of possible piles of bricks, one that corresponds to the desired house. He uses a plan that maps each brick (in principle if not in practice) to a specific position in space. The plan provides the builder with the information he needs to build the house. Similarly, the living cell must select from the vast number of all possible proteins the tiny fraction that corresponds to proteins with useful functions. The cell similarly needs to have some kind of plan or template and for this it uses DNA.
There is, however, (at least in animal and plant cells) a physical problem that must be overcome if DNA is to direct protein synthesis. DNA is held within the nucleus (a membrane-bound sac inside cells) of animal cells but the ribosomes are located outside it in the cytoplasm (the cellular material outside the nucleus). One possible solution would be for the DNA to pass through the nuclear membrane to the ribosomes where it is needed to direct protein synthesis. However DNA is a huge molecule, millions or even billions of bases long and it would not be easy for it to squeeze out through the membrane’s small pores. What actually happens is that the information held in DNA is copied into a smaller, mobile analogue of DNA, known as RNA. RNA has all the same bases as DNA (well nearly all, it uses a base called uracil instead of thymine) on a sugar phosphate backbone, just like DNA. The only difference is that the sugar that goes into its backbone is ribose rather than deoxyribose (hence RNA rather than DNA). Since the bases are nearly the same, a single DNA strand can pair with a complementary RNA strand (the RNA uracil pairs with adenine) to form a DNA::RNA hybrid double helix. An enzyme called RNA polymerase then makes RNA copies of DNA genes. The RNA copy, called messenger RNA or simply mRNA is usually only one to several thousand bases long and can easily travel out through the pores in the nuclear membrane to reach a ribosome. It then locks into the machinery and tells the ribosome which protein to make.
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.
