The Selfish Gene Page 5
A sperm, with its 23 chromosomes, is made by the meiotic division of one of the ordinary 46-chromosome cells in the testicle. Which 23 are put into any given sperm cell? It is clearly important that a sperm should not get just any old 23 chromosomes: it mustn't end up with two copies of Volume 13 and none of Volume 17. It would theoretically be possible for an individual to endow one of his sperms with chromosomes which came, say, entirely from his mother; that is Volume 1b, 2b, 3b,..., 23b. In this unlikely event, a child conceived by the sperm would inherit half her genes from her paternal grandmother, and none from her paternal grandfather. But in fact this kind of gross, whole-chromosome distribution does not happen. The truth is rather more complex. Remember that the volumes (chromosomes) are to be thought of as loose-leaf binders. What happens is that, during the manufacture of the sperm, single pages, or rather multi-page chunks, are detached and swapped with the corresponding chunks from the alternative volume. So, one particular sperm cell might make up its Volume 1 by taking the first 65 pages from Volume 1a, and pages 66 to the end from Volume 1b. This sperm cell's other 22 volumes would be made up in a similar way. Therefore every sperm cell made by an individual is unique, even though all his sperms assembled their 23 chromosomes from bits of the same set of 46 chromosomes. Eggs are made in a similar way in ovaries, and they too are all unique.
The real-life mechanics of this mixing are fairly well understood. During the manufacture of a sperm (or egg), bits of each paternal chromosome physically detach themselves and change places with exactly corresponding bits of maternal chromosome. (Remember that we are talking about chromosomes that came originally from the parents of the individual making the sperm, i.e., from the paternal grandparents of the child who is eventually conceived by the sperm). The process of swapping bits of chromosome is called crossing over. It is very important for the whole argument of this book. It means that if you got out your microscope and looked at the chromosomes in one of your own sperms (or eggs if you are female) it would be a waste of time trying to identify chromosomes that originally came from your father and chromosomes that originally came from your mother. (This is in marked contrast to the case of ordinary body cells (see page 25). Any one chromosome in a sperm would be a patchwork, a mosaic of maternal genes and paternal genes.
The metaphor of the page for the gene starts to break down here. In a loose-leaf binder a whole page may be inserted, removed or exchanged, but not a fraction of a page. But the gene complex is just a long string of nucleotide letters, not divided into discrete pages in an obvious way at all. To be sure, there are special symbols for end of PROTEIN CHAIN MESSAGE and START OF PROTEIN CHAIN MESSAGE written in the same four-letter alphabet as the protein messages themselves. In between these two punctuation marks are the coded instructions for making one protein. If we wish, we can define a single gene as a sequence of nucleotide letters lying between a start and an end symbol, and coding for one protein chain. The word cistron has been used for a unit defined in this way, and some people use the word gene interchangeably with cistron. But crossing-over does not respect boundaries between cistrons. Splits may occur within cistrons as well as between them. It is as though the architect's plans were written out, not on discrete pages, but on 46 rolls of ticker tape. Cistrons are not of fixed length. The only way to tell where one cistron ends and the next begins would be to read the symbols on the tape, looking for end of message and start of message symbols. Crossing-over is represented by taking matching paternal and maternal tapes, and cutting and exchanging matching portions, regardless of what is written on them.
In the title of this book the word gene means not a single cistron but something more subtle. My definition will not be to everyone's taste, but there is no universally agreed definition of a gene. Even if there were, there is nothing sacred about definitions. We can define a word how we like for our own purposes, provided we do so clearly and unambiguously. The definition I want to use comes from G. C. Williams. A gene is defined as any portion of chromosomal material that potentially lasts for enough generations to serve as a unit of natural selection. In the words of the previous chapter, a gene is a replicator with high copying-fidelity. Copying-fidelity is another way of saying longevity-in-the-form-of-copies and I shall abbreviate this simply to longevity. The definition will take some justifying.
On any definition, a gene has to be a portion of a chromosome. The question is, how big a portion-how much of the ticker tape? Imagine any sequence of adjacent code-letters on the tape. Call the sequence a genetic unit. It might be a sequence of only ten letters within one cistron; it might be a sequence of eight cistrons; it might start and end in mid-cistron. It will overlap with other genetic units. It will include smaller units, and it will form part of larger units. No matter how long or short it is, for the purposes of the present argument, this is what we are calling a genetic unit. It is just a length of chromosome, not physically differentiated from the rest of the chromosome in any way.
Now comes the important point. The shorter a genetic unit is, the longer-in generations-it is likely to live. In particular, the less likely it is to be split by any one crossing-over. Suppose a whole chromosome is, on average, likely to undergo one cross-over every time a sperm or egg is made by meiotic division, and this cross-over can happen anywhere along its length. If we consider a very large genetic unit, say half the length of the chromosome, there is a 50 per cent chance that the unit will be split at each meiosis. If the genetic unit we are considering is only 1 per cent of the length of the chromosome, we can assume that it has only a 1 per cent chance of being split in any one meiotic division. This means that the unit can expect to survive for a large number of generations in the individual's descendants. A single cistron is likely to be much less than 1 per cent of the length of a chromosome. Even a group of several neighbouring cistrons can expect to live many generations before being broken up by crossing over.
The average life-expectancy of a genetic unit can conveniently be expressed in generations, which can in turn be translated into years. If we take a whole chromosome as our presumptive genetic unit, its life story lasts for only one generation. Suppose it is your chromosome number 8a, inherited from your father. It was created inside one of your father's testicles, shortly before you were conceived. It had never existed before in the whole history of the world. It was created by the meiotic shuffling process, forged by the coming together of pieces of chromosome from your paternal grandmother and your paternal grandfather. It was placed inside one particular sperm, and it was unique. The sperm was one of several millions, a vast armada of tiny vessels, and together they sailed into your mother. This particular sperm (unless you are a non-identical twin) was the only one of the flotilla which found harbour in one of your mother's eggs-that is why you exist. The genetic unit we are considering, your chromosome number 8a, set about replicating itself along with all the rest of your genetic material. Now it exists, in duplicate form, all over your body. But when you in your turn come to have children, this chromosome will be destroyed when you manufacture eggs (or sperms). Bits of it will be interchanged with bits of your maternal chromosome number 8b. In any one sex cell, a new chromosome number 8 will be created, perhaps 'better' than the old one, perhaps 'worse', but, barring a rather improbable coincidence, definitely different, definitely unique. The life-span of a chromosome is one generation.
What about the life-span of a smaller genetic unit, say 1/100 of the length of your chromosome 8a? This unit too came from your father, but it very probably was not originally assembled in him. Following the earlier reasoning, there is a 99 per cent chance that he received it intact from one of his two parents. Suppose it was from his mother, your paternal grandmother. Again, there is a 99 per cent chance that she inherited it intact from one of her parents. Eventually, if we trace the ancestry of a small genetic unit back far enough, we will come to its original creator. At some stage it must have been created for the first time inside a testicle or an ovary of one of your ancestors.
Let me repeat the rather special sense in which I am using the word 'create'. The smaller sub-units which make up the genetic unit we are considering may well have existed long before. Our genetic unit was created at a particular moment only in the sense that the particular arrangement of sub-units by which it is defined did not exist before that moment. The moment of creation may have occurred quite recently, say in one of your grandparents. But if we consider a very small genetic unit, it may have been first assembled in a much more distant ancestor, perhaps an ape-like pre-human ancestor. Moreover, a small genetic unit inside you may go on just as far into the future, passing intact through a long line of your descendants.
Remember too that an individual's descendants constitute not a single line but a branching line. Whichever of your ancestors it was who 'created' a particular short length of your chromosome 8a, he or she very likely has many other descendants besides you. One of your genetic units may also be present in your second cousin. It may be present in me, and in the Prime Minister, and in your dog, for we all share ancestors if we go back far enough. Also the same small unit might be assembled several times independently by chance: if the unit is small, the coincidence is not too improbable. But even a close relative is unlikely to share a whole chromosome with you. The smaller a genetic unit is, the more likely it is that another individual shares it-the more likely it is to be represented many times over in the world, in the form of copies.
The chance coming together, through crossing-over, of previously existing sub-units is the usual way for a new genetic unit to be formed. Another way-of great evolutionary importance even though it is rare-is called point mutation. A point mutation is an error corresponding to a single misprinted letter in a book. It is rare, but clearly the longer a genetic unit is, the more likely it is to be altered by a mutation somewhere along its length.
Another rare kind of mistake or mutation which has important long-term consequences is called inversion. A piece of chromosome detaches itself at both ends, turns head over heels, and reattaches itself in the inverted position. In terms of the earlier analogy, this would necessitate some renumbering of pages. Sometimes portions of chromosomes do not simply invert, but become reattached in a completely different part of the chromosome, or even join up with a different chromosome altogether. This corresponds to the transfer of a wad of pages from one volume to another. The importance of this kind of mistake is that, though usually disastrous, it can occasionally lead to the close linkage of pieces of genetic material which happen to work well together. Perhaps two cistrons which have a beneficial effect only when they are both present-they complement or reinforce each other in some way-will be brought close to each other by means of inversion. Then natural selection may tend to favour the new 'genetic unit' so formed, and it will spread through the future population. It is possible that gene complexes have, over the years, been extensively rearranged or 'edited' in this kind of way.
One of the neatest examples of this concerns the phenomenon known as mimicry. Some butterflies taste nasty. They are usually brightly and distinctively coloured, and birds learn to avoid them by their 'warning' marks. Now other species of butterfly that do not taste nasty cash in. They mimic the nasty ones. They are born looking like them in colour and shape (but not taste). They frequently fool human naturalists, and they also fool birds. A bird who has once tasted a genuinely nasty butterfly tends to avoid all butterflies that look the same. This includes the mimics, and so genes for mimicry are favoured by natural selection. That is how mimicry evolves.
There are many different species of 'nasty' butterfly and they do not all look alike. A mimic cannot resemble all of them: it has to commit itself to one particular nasty species. In general, any particular species of mimic is a specialist at mimicking one particular nasty species. But there are species of mimic that do something very strange. Some individuals of the species mimic one nasty species; other individuals mimic another. Any individual who was intermediate or who tried to mimic both would soon be eaten; but such intermediates are not born. Just as an individual is either definitely male or definitely female, so an individual butterfly mimics either one nasty species or the other. One butterfly may mimic species A while his brother mimics species B.
It looks as though a single gene determines whether an individual will mimic species A or species B. But how can a single gene determine all the multifarious aspects of mimicry-colour, shape, spot pattern, rhythm of flight? The answer is that one gene in the sense of a cistron probably cannot. But by the unconscious and automatic 'editing' achieved by inversions and other accidental rearrangements of genetic material, a large cluster of formerly separate genes has come together in a tight linkage group on a chromosome. The whole cluster behaves like a single gene-indeed, by our definition it now is a single gene-and it has an 'allele' which is really another cluster. One cluster contains the cistrons concerned with mimicking species A; the other those concerned with mimicking species B. Each cluster is so rarely split up by crossing-over that an intermediate butterfly is never seen in nature, but they do very occasionally turn up if large numbers of butterflies are bred in the laboratory.
I am using the word gene to mean a genetic unit that is small enough to last for a large number of generations and to be distributed around in the form of many copies. This is not a rigid all-or-nothing definition, but a kind of fading-out definition, like the definition of 'big' or 'old'. The more likely a length of chromosome is to be split by crossing-over, or altered by mutations of various kinds, the less it qualifies to be called a gene in the sense in which I am using the term. A cistron presumably qualifies, but so also do larger units. A dozen cistrons may be so close to each other on a chromosome that for our purposes they constitute a single long-lived genetic unit. The butterfly mimicry cluster is a good example. As the cistrons leave one body and enter the next, as they board sperm or egg for the journey into the next generation, they are likely to find that the little vessel contains their close neighbours of the previous voyage, old shipmates with whom they sailed on the long odyssey from the bodies of distant ancestors. Neighbouring cistrons on the same chromosome form a tightly-knit troupe of travelling companions who seldom fail to get on board the same vessel when meiosis time comes around.
To be strict, this book should be called not The Selfish Cistron nor The Selfish Chromosome, but The slightly selfish big bit of chromosome and the even more selfish little bit of chromosome. To say the least this is not a catchy tide so, defining a gene as a little bit of chromosome which potentially lasts for many generations, I call the book The Selfish Gene.
We have now arrived back at the point we left at the end of Chapter i. There we saw that selfishness is to be expected in any entity that deserves the title of a basic unit of natural selection. We saw that some people regard the species as the unit of natural selection, others the population or group within the species, and yet others the individual. I said that I preferred to think of the gene as the fundamental unit of natural selection, and therefore the fundamental unit of self-interest. What I have now done is to define the gene in such a way that I cannot really help being right!
Natural selection in its most general form means the differential survival of entities. Some entities live and others die but, in order for this selective death to have any impact on the world, an additional condition must be met. Each entity must exist in the form of lots of copies, and at least some of the entities must be potentially capable of surviving-in the form of copies-for a significant period of evolutionary time. Small genetic units have these properties: individuals, groups, and species do not. It was the great achievement of Gregor Mendel to show that hereditary units can be treated in practice as indivisible and independent particles. Nowadays we know that this is a little too simple. Even a cistron is occasionally divisible and any two genes on the same chromosome are not wholly independent. What I have done is to define a gene as a unit which, to a high degree, approaches the ideal of indivisible partic
ulateness. A gene is not indivisible, but it is seldom divided. It is either definitely present or definitely absent in the body of any given individual. A gene travels intact from grandparent to grandchild, passing straight through the intermediate generation without being merged with other genes. If genes continually blended with each other, natural selection as we now understand it would be impossible. Incidentally, this was proved in Darwin's lifetime, and it caused Darwin great worry since in those days it was assumed that heredity was a blending process. Mendel's discovery had already been published, and it could have rescued Darwin, but alas he never knew about it: nobody seems to have read it until years after Darwin and Mendel had both died. Mendel perhaps did not realize the significance of his findings, otherwise he might have written to Darwin.
Another aspect of the particulateness of the gene is that it does not grow senile; it is no more likely to die when it is a million years old than when it is only a hundred. It leaps from body to body down the generations, manipulating body after body in its own way and for its own ends, abandoning a succession of mortal bodies before they sink in senility and death.
The genes are the immortals, or rather, they are defined as genetic entities that come close to deserving the title. We, the individual survival machines in the world, can expect to live a few more decades. But the genes in the world have an expectation of life that must be measured not in decades but in thousands and millions of years.