The Blind Watchmaker (21 page)

When the information in a computer memory has been read from a particular location, one of two things may happen to it. It can either simply be written somewhere else, or it can become involved in some ‘action’. Being written somewhere else means being copied. We have already seen that DNA is readily copied from one cell to a new cell, and that chunks of DNA may be copied from one individual to another individual, namely its child. ‘Action’ is more complicated. In computers, one kind of action is the execution of program instructions. In my computer’s ROM, location numbers 64489, 64490 and 64491, taken together, contain a particular pattern of contents - Is and Os which when interpreted as instructions, result in the computer’s little loudspeaker uttering a blip sound. This bit pattern is 101011010011000011000000. There is nothing inherently blippy or noisy about that bit pattern. Nothing about it tells you that it will have that effect on the loudspeaker. It has that effect only because of the way the rest of the computer is wired up. In the same way, patterns in the DNA four-letter code have effects, for instance on eye colour or behaviour, but these effects are not inherent in the DNA data patterns themselves. They have their effects only as a result of the way the rest of the embryo develops, which in turn is influenced by the effects of patterns in other parts of the DNA. This interaction between genes will be a main theme of Chapter 7.

Before they can be involved in any kind of action, the code symbols of DNA have to be translated into another medium. They are first transcribed into exactly corresponding RNA symbols. RNA also has a four-letter alphabet. From here, they are translated into a different kind of polymer called a polypeptide or protein. It might be called a polyamino acid, because the basic units are amino acids. There are 20 kinds of amino acids in living cells. All biological proteins are chains made of these 20 basic building-blocks. Although a protein is a chain of amino acids, most of them don’t remain long and stringy. Each chain coils up into a complicated knot, the precise shape of which is determined by the order of amino acids. This knot shape therefore never varies for any given sequence of amino acids. The sequence of amino acids in turn is precisely determined by the code symbols in a length of DNA (via RNA as an intermediary). There is a sense, therefore, in which the threedimensional coiled shape of a protein is determined by the onedimensional sequence of code symbols in the DNA.

The translation procedure embodies the celebrated three-letter ‘genetic code’. This is a dictionary, in which each of the 64 (4 x 4 x 4) possible
triplets
of DNA (or RNA) symbols is translated into one of the 20 amino acids or a ‘stop reading’ symbol. There are three of these ‘stop reading’ punctuation marks. Many of the amino acids are coded by more than one triplet (as you might have guessed from the fact that there are 64 triplets and only 20 amino acids). The whole translation, from strictly sequential DNA ROM to precisely invariant threedimensional protein shape, is a remarkable feat of digital information technology. Subsequent steps by which genes influence bodies are a little less obviously computer-like.

Every living cell, even a single bacterial cell, can be thought of as a gigantic chemical factory. DNA patterns, or genes, exert their effects by influencing the course of events in the chemical factory, and they do this via their influence on the threedimensional shape of protein molecules. The word gigantic may seem surprising for a cell, especially when you remember that 10 million bacterial cells could sit on the surface of a pin’s head. But you will also remember that each of these cells is capable of holding the whole text of the New Testament and, moreover, it
is
gigantic when measured by the number of sophisticated machines that it contains. Each machine is a large protein molecule, put together under the influence of a particular stretch of DNA.

Protein molecules called enzymes are machines in the sense that each one causes a particular chemical reaction to take place. Each kind of protein machine churns out its own particular chemical product. To do this it uses raw materials that are drifting around in the cell, being, very probably, the products of other protein machines. To get an idea of the size of these protein machines, each one is made of about 6,000 atoms, which is very large by molecular standards. There are about a million of these large pieces of apparatus in a cell, and there are more than 2,000 different kinds of them, each kind specialized to do a particular operation in the chemical factory - the cell. It is the characteristic chemical products of such enzymes that give a cell its individual shape and behaviour.

Since all body cells contain the same genes, it might seem surprising that all body cells aren’t the same as each other. The reason is that a different subset of genes is
read
in different kinds of cells, the others being ignored. In liver cells, those parts of the DNA ROM specifically relevant to the building of kidney cells are not read, and vice versa. The shape and behaviour of a cell depend upon which genes inside that cell are being read and translated into their protein products. This in turn depends on the chemicals already in the cell, which depends partly on which genes have previously been read in the cell, and partly on neighbouring cells. When one cell divides into two, the two daughter cells aren’t necessarily the same as each other. In the original fertilized egg, for instance, certain chemicals congregate at one end of the cell, others at the other end. When such a polarized cell divides, the two daughter cells receive different chemical allocations. This means that different genes will be read in the two daughter cells, and a kind of self-reinforcing divergence gets going. The final shape of the whole body, the size of its limbs, the wiring up of its brain, the timing of its behaviour patterns, are all the indirect consequences of interactions between different kinds of cells, whose differences in their turn arise through different genes being read. These diverging processes are best thought of as locally autonomous in the manner of the ‘recursive’ procedure of Chapter 3, rather than as coordinated in some grand central design.

‘Action’, in the sense used in this chapter, is what a geneticist is talking about when he mentions the ‘phenotypic effect’ of a gene. DNA has effects upon bodies, upon eye colour, hair crinkliness, strength of aggressive behaviour and thousands of other attributes, all of which are called phenotypic effects. DNA exerts these effects initially locally, after being read by RNA and translated into protein chains, which then affect cell shape and behaviour. This is one of the two ways in which the information in the pattern of DNA can be read out. The other way is that it can be duplicated into a new DNA strand. This is the copying that we discussed earlier.

There is a fundamental distinction between these two routes of transmission of the DNA information, vertical and horizontal transmission. The information is transmitted vertically to other DNA in cells (that make other cells) that make sperms or eggs. Hence it is transmitted vertically to the next generation and then, vertically again, to an indefinite number of future generations. I shall call this ‘archival DNA’. It is potentially immortal. The succession of cells along which archival DNA travels is called the germ line. The germ line is that set of cells, within a body, which is ancestral to sperms or eggs and hence ancestral to future generations. DNA is also transmitted
sideways
or horizontally: to DNA in non-germ-line cells such as liver cells or skin cells; within such cells to RNA, thence to protein and various effects on embryonic development and therefore on adult form and behaviour. You can think of horizontal transmission and vertical transmission as corresponding to the two sub-programs called DEVELOPMENT and REPRODUCTION in Chapter 3.

Natural selection is all about the differential success of rival DNA in getting itself transmitted vertically in the species archives. ‘Rival DNA’ means alternative contents of particular addresses in the chromosomes of the species. Some genes are more successful than rival genes at remaining in the archives. Although
vertical
transmission down the archives of the species is ultimately what ‘success’ means, the criterion for success is normally the
action
that the genes have on bodies, by means of their
sideways
transmission. This, too, is just like the biomorph computer model. For instance, suppose that in tigers there is a particular gene which, by means of its sideways influence in cells of the jaw, causes the teeth to be a little sharper than those that would be grown under the influence of a rival gene. A tiger with extra-sharp teeth can kill prey more efficiently than a normal tiger; hence it has more offspring; hence it passes on, vertically, more copies of the gene that makes sharp teeth. It passes on all its other genes at the same time, of course, but only the specific ‘sharp-teeth gene’ will find itself, on
average
, in the bodies of sharp-toothed tigers. The gene itself benefits, in terms of its vertical transmission, from the average effects that it has on a whole series of bodies.

DNA’s performance as an archival medium is spectacular. In its capacity to preserve a message it far outdoes tablets of stone. Cows and pea plants (and, indeed, all the rest of us) have an almost identical gene called the histone H4 gene. The DNA text is 306 characters long. We can’t say that it occupies the same addresses in all species, because we can’t meaningfully compare address labels across species. But what we can say is that there is a length of 306 characters in cows, which is virtually identical to a length of 306 characters in peas. Cows and peas differ from each other in only two characters out of these 306. We don’t know exactly how long ago the common ancestor of cows and peas lived, but fossil evidence suggests that it was somewhere between 1,000 and 2,000 million years ago. Call it 1.5 billion years ago. Over this unimaginably (for humans) long time, each of the two lineages that branched from that remote ancestor has preserved 305 out of the 306 characters (on average: it could be that one lineage has preserved all 306 of them and the other has preserved 304). Letters carved on gravestones become unreadable in mere hundreds of years.

In a way the conservation of the histone-H4 DNA document is even more impressive because, unlike tablets of stone, it is not the same physical structure that lasts and preserves the text. It is repeatedly being copied and recopied as the generations go by, like the Hebrew scriptures which were ritually copied by scribes every 80 years to forestall their wearing-out. It is hard to estimate exactly how many times the histone H4 document has been recopied in the lineage leading to cows from the common ancestor with peas, but it is probably as many as 20 billion times. It is also hard to find a yardstick with which to compare the preservation of more than 99 per cent of information in 20 billion successive copyings. We can try using a version of the game of grandmothers’ whispers. Imagine 20 billion typists sitting in a row. The line of typists would reach right round the Earth 500 times. The first typist writes a page of a document and hands it to his neighbour. He copies it and hands his copy to the next one. He copies it again and hands it on to the next, and so on. Eventually, the message reaches the end of the line, and we read it (or rather our 12,000th great grandchildren do, assuming that all the typists have a speed typical of a good secretary). How faithful a rendering of the original message would it be?

To answer this we have to make some assumption about the accuracy of the typists. Let’s twist the question round the other way. How good would each typist have to be, in order to match the DNA’s performance? The answer is almost too ludicrous to express. For what it is worth, every typist would have to have an error rate of about one in a trillion; that is, he would have to be accurate enough to make only a single error in typing the Bible 250,000 times at a stretch. A good secretary in real life has an error rate of about one per page. This is about half a billion times the error rate of the histone H4 gene. A line of real-life secretaries would degrade a text to 99 per cent of its original letters by the 20th member of the line of 20 billion. By the 10,000th member of the line, less than 1 per cent of the original text would survive. This point of near total degradation would be reached before 99.9995 per cent of the typists had even seen it. This whole comparison has been a bit of a cheat, but in an interesting and revealing respect. I gave the impression that what we are measuring is copying errors. But the histone H4 document hasn’t just been copied, it has been subjected to natural selection. Histone is vitally important for survival. It is used in the structural engineering of chromosomes. Maybe lots more mistakes in
copying
the histone H4 gene occurred, but the mutant organisms did not survive, or at least did not reproduce. To make the comparison fair, we should have to assume that built into each typist’s chair is a gun, wired up so that if he makes a mistake he is summarily shot, his place being taken by a reserve typist (squeamish readers may prefer to imagine a spring-loaded ejector seat gently catapulting miscreant typists out of the line, but the gun gives a more realistic picture of natural selection).

So, this method of measuring the conservatism of DNA, by looking at the number of changes that have actually occurred during geological time, compounds genuine copying fidelity with the filtering effects of natural selection. We see only the descendants of successful DNA changes. The ones that led to death are obviously not with us. Can we measure the actual copying fidelity on the ground, before natural selection gets to work on each new generation of genes? Yes, this is the inverse of what is known as the mutation rate, and it can be measured. The probability of any particular letter being miscopied on any one copying occasion turns out to be a little more than one in a billion. The difference between this, the mutation rate, and the lower rate at which change has actually been incorporated in the histone gene during evolution, is a measure of the effectiveness of natural selection in preserving this ancient document.