The Extended Phenotype: The Long Reach of the Gene (Popular Science) (33 page)

While awaiting further evidence for and against hypotheses of the Cavalier-Smith variety, the thing to notice in the present context is that they are hypotheses made in the traditional mould; they are based on the idea that DNA, like any other aspect of an organism, is selected because it does the organism some good. The selfish DNA hypothesis is based on an inversion of this assumption: phenotypic characters are there because they help DNA to replicate itself, and if DNA can find quicker and easier ways to replicate itself, perhaps bypassing conventional phenotypic expression, it will be selected to do so. Even if the Editor of
Nature
(Vol. 285, p. 604, 1980) goes a bit far in describing it as ‘mildly shocking’, the theory of selfish DNA is in a way revolutionary. But once we deeply imbibe the fundamental truth that an organism is a tool of DNA, rather than the other way around, the idea of ‘selfish DNA’ becomes compelling, even obvious.

The living cell, especially the nucleus in eukaryotes, is packed with the active machinery of nucleic acid replication and recombination. DNA polymerase readily catalyses the replication of any DNA, regardless of whether or not that DNA is meaningful in terms of the genetic code. ‘Snipping out’ of DNA, and ‘splicing in’ of other bits of DNA, are also parts of the normal stock in trade of the cellular apparatus, for they occur every time there is a crossover or other type of recombination event. The fact that inversions and other translocations so readily occur, further testifies to the casual ease with which chunks of DNA may be cut out of one part of the genome, and spliced into another part. Replicability and ‘spliceability’ seem to be among the most salient features of DNA in its natural environment (Richmond 1979) of cellular machinery.

Given the possibilities of such an environment, given the existence of cellular factories set up for the replication and splicing of DNA, it is only to be expected that natural selection would favour DNA variants that are able
to exploit the conditions to their own advantage. Advantage, in this case, simply means multiple replication in germ-lines. Any variety of DNA whose properties happen to make it readily replicated will automatically become commoner in the world.

What might such properties be? Paradoxically, we are most familiar with the more indirect, elaborate, and roundabout methods by which DNA molecules secure their future. These are their phenotypic effects on bodies, achieved by the proximal route of controlling protein synthesis, and hence by the more distal routes of controlling embryonic development of morphology, physiology and behaviour. But there are also much more direct and simple ways in which varieties of DNA can spread at the expense of rival varieties. It is becoming increasingly evident that, in addition to the large, orderly chromosomes with their well-regimented gavotte, cells are home to a motley riff-raff of DNA and RNA fragments, cashing in on the perfect environment provided by the cellular apparatus.

These replicating fellow-travellers go by various names depending on size and properties: plasmids, episomes, insertion sequences, plasmons, virions, transposons, replicons, viruses. Whether they should be regarded as rebels who have broken away from the chromosomal gavotte, or as invading parasites from outside, seems to matter less and less. To take a parallel, we may regard a pond, or a forest, as a community with a certain structure, and even a certain stability. But the structure and stability are maintained in the face of a constant turnover of participants. Individuals immigrate and emigrate, new ones are born and old ones die. There is a fluidity, a jumping in and out of component parts, so that it becomes meaningless to try to distinguish ‘true’ community members from foreign invaders. So it is with the genome. It is not a static structure, but a fluid community. ‘Jumping genes’ immigrate and emigrate (Cohen 1976).

Since the range of possible hosts in nature at least for transforming DNA and for plasmids such as RP4 is so large, one feels that at least in Gram-negative bacteria all populations may indeed be connected. It is known that bacterial DNA can be expressed in widely different host species … It may indeed be impossible to view bacterial evolution in terms of simple family trees; rather, a network, with converging as well as diverging junctions, may be a more appropriate metaphor [Broda 1979, p. 140].

Some authors speculate that the network is not confined to bacterial evolution (e.g. Margulis 1976).

There is substantial evidence that organisms are not limited for their evolution to genes that belong to the gene pool of their species. Rather it seems more plausible that in the time-scale of evolution the
whole of the gene pool of the biosphere is available to all organisms and that the more dramatic steps and apparent discontinuities in evolution are in fact attributable to very rare events involving the adoption of part or all of a foreign genome. Organisms and genomes may thus be regarded as compartments of the biosphere through which genes in general circulate at various rates and in which individual genes and operons may be incorporated if of sufficient advantage …’ [Jeon & Danielli 1971].

That eukaryotes, including ourselves, may not be insulated from this hypothetical genetic traffic is suggested by the fast-growing success of the technology of ‘genetic engineering’, or gene manipulation. The legal definition of gene manipulation in Britain is ‘the formation of new combinations of heritable material by the insertion of nucleic acid molecules, produced by whatever means outside the cell, into any virus, bacterial plasmid or other vector system so as to allow their incorporation into a host organism in which they do not naturally occur but in which they are capable of continued propagation’ (Old & Primrose 1980, p. 1). But of course human genetic engineers are beginners in the game. They are just learning to tap the expertise of the natural genetic engineers, the viruses and plasmids that have been selected to make their living at the trade.

Perhaps the greatest feat of natural genetic engineering on the grand scale is the complex of manipulations associated with sexual reproduction in eukaryotes: meiosis, crossing-over and fertilization. Two of our foremost modern evolutionists have failed to explain to their own satisfaction the advantage of this extraordinary procedure for the individual organism (Williams 1975; Maynard Smith 1978a). As Maynard Smith (1978a, p. 113) and Williams (1979) both note, this may be one area where, if nowhere else, we shall have to switch our attention away from individual organisms to true replicators. When we try to solve the paradox of the cost of meiosis, perhaps instead of worrying about how sex helps the
organism
we should search for replicating ‘engineers’ of meiosis, intracellular agents which actually cause meiosis to happen. These hypothetical engineers, fragments of nucleic acid which might lie inside or outside the chromosomes, would have to achieve their own replication success as a byproduct of forcing meiosis upon the organism. In bacteria, recombination is achieved by a separate fragment of DNA or ‘sex factor’ which, in older textbooks, was treated as a part of the bacterium’s own adaptive machinery, but which is better regarded as a replicating genetic engineer working for its own good. In animals, centrioles are thought to be self-replicating entities with their own DNA, like mitochondria, although unlike mitochondria they often pass through the male as well as the female line. Although at present it is just a joke to picture chromosomes being dragged kicking and screaming into the second anaphase
by ruthlessly selfish centrioles or other miniature genetic engineers, stranger ideas have become commonplace in the past. And, after all, orthodox theorizing has so far failed to dent the paradox of the cost of meiosis.

Orgel and Crick (1980) say much the same about the lesser paradox of variable C values and about the selfish DNA theory to account for it: ‘The main facts are, at first sight, so odd that only a somewhat unconventional idea is likely to explain them.’ By a combination of fact and daydreamed extrapolation, I have tried to set a stage on to which selfish DNA itself can enter almost unnoticed; to paint a backdrop against which selfish DNA will appear, not unconventional but almost inescapable. DNA that is not translated into protein, whose codons would spell meaningless gibberish if they ever were translated, may yet vary in its replicability, its spliceability, and its resistance to detection and deletion by the debugging routines of the cellular machinery. ‘Intragenomic selection’ can therefore lead to an increase in the amount of certain types of meaningless, or untranscribed, DNA, littered around and cluttering up the chromosomes. Translated DNA, too, may be subject to this kind of selection, although here the intragenomic selection pressures will probably be swamped by more powerful pressures, positive and negative, resulting from conventional phenotypic effects.

Conventional selection results in changes in the frequency of replicators relative to their alleles at defined loci on the chromosomes of populations. Intragenomic selection of selfish DNA is a different kind of selection. Here we are not dealing with the relative success of alleles at one locus in a gene-pool, but with the spreadability of certain kinds of DNA to
different
loci or the creation of new loci. Moreover, the selection of selfish DNA is not limited to the time-scale of individual generations; it can selectively increase in any mitotic cell division in the germ-lines of developing bodies.

In conventional selection, the variation on which selection acts is produced, ultimately, by mutation, but we usually think of it as mutation within the constraints of an orderly system of loci: mutation produces a variant gene at a named locus. It is therefore possible to think of selection as choosing among alleles at such a discrete locus. Mutation in the larger sense, however, includes more radical changes in the genetic system, minor ones such as inversions, and major ones such as changes in chromosome number or ploidy, and changes from sexuality to asexuality and vice versa. These larger mutations ‘change the rules of the game’ but they are still, in various senses, subject to natural selection. Intragenomic selection for selfish DNA belongs in the list of unconventional types of selection, not involving choice among alleles at a discrete locus.

Selfish DNA is selected for its power to spread ‘laterally’, to get itself duplicated into new loci elsewhere in the genome. It does not spread at the expense of a particular set of alleles, in the way that, say, a gene for melanism in moths spreads in industrial areas at the expense of its alleles at
the same locus. It is this that distinguishes it, as a ‘laterally spreading outlaw’, from the ‘allelic outlaws’ which were the subject of the previous chapter. Lateral spreading to new loci is like the spread of a virus through a population, or like the spread of cancer cells through a body. Orgel and Crick indeed refer to the spreading of functionless replicators as a ‘cancer of the genome’.

As for the qualities which are actually likely to be favoured in the selection of selfish DNA, I would have to be a molecular biologist in order to predict them in detail. One does not have to be a molecular biologist, however, to surmise that they might be classified into two main classes: qualities that make for ease of duplication and insertion, and qualities that make it difficult for defence mechanisms of the cell to seek them out and destroy them. Just as a cuckoo egg seeks protection by mimicking the host eggs which legitimately inhabit the nest, so selfish DNA might evolve mimetic qualities that ‘make it more like ordinary DNA and so, perhaps, less easy to remove’ (Orgel & Crick). Just as a full understanding of cuckoo adaptations is likely to require a knowledge of the perceptual systems of hosts, so a full appreciation of the details of selfish DNA adaptations will require detailed knowledge of exactly how DNA polymerase works, exactly how snipping and splicing occur, exactly what goes on in molecular ‘proof-reading’. While full knowledge of these matters can only come from detailed research work of the kind that molecular biologists have so brilliantly succeeded in before, it is, perhaps, not too much to hope that molecular biologists might be aided in their research by the realization that DNA is not working for the good of the cell but for the good of itself. The machinery of replication, splicing, and proof-reading may be better understood if it is seen as in part the product of a ruthless arms race. The point may be emphasized with the aid of an analogy.

Imagine that Mars is a Utopia in which there is complete trust, total harmony, no selfishness and no deceit. Now imagine a scientist from Mars trying to make sense of human life and technology. Suppose he studied one of our large data processing centres—an electronic computer with its associated machinery of duplication, editing and error-correction. If he made the assumption—natural to his own society—that the machinery had been designed for the common good, he would go a long way towards understanding it. Error-correcting devices, for instance, would clearly be designed to combat the inevitable and non-malevolent Second Law of Thermodynamics. But certain aspects would remain puzzling. He would make no sense of the elaborate and costly systems of security and protection: secret passwords and code numbers that have to be typed in by computer users. If our Martian examined a military electronic communication system he might diagnose its purpose as the rapid and efficient transmission of useful information, and he might therefore be baffled by the trouble and expense to
which the system seems to go in order to encode its messages in a way which is obscure and hard to decode. Is this not wanton and absurd inefficiency? Brought up as he is in a trusting Utopia, it might require a major flash of revolutionary insight for our Martian to see that much of human technology only makes sense when you realize that humans
distrust
each other, that some humans work against the best interests of other humans. There is a struggle between those who wish to obtain illicit information from a communication system and those who wish to withhold that information from them. Much of human technology is the product of arms races and can only be understood in those terms.