Hen’s Teeth and Horse’s Toes

by Stephen Jay Gould

  Conventional arguments for the existence of middle-repetitive DNA follow the usual Darwinian perspective. Evolution is about the struggle of organisms to leave more surviving offspring in future generations. This struggle operates by natural selection and selection is a potent editor. Major features of organisms—and some 25 percent of the genetic material cannot be minor—must exist because they provide some advantages to organisms in the struggle for life. We must, in other words, find a function for middle-repetitive DNA in terms of advantages to the bodies that carry it.

  Rumblings of claims for nonadaptive and nonfunctional status have been heard from time to time (selfish DNA is the first, and more subtle, explosion for this perspective). Still, as Doolittle and Sapienza detail in their article, the overwhelming majority of proposals have hewed to Darwinian orthodoxy: they assume that middle-repetitive DNA cannot exist in such amounts unless it confers direct adaptive benefits upon organisms. (I will save myself some words from now on by simply writing “repetitive DNA” when I mean “middle-repetitive DNA” only.)

  The conventional adaptationist hypotheses have fallen into two classes: one, I believe, obviously wrong on (unrecognized) principle; the other undoubtedly correct in part (I do not believe that all repetitive DNA is selfish DNA). The unreasonable arguments postulate what I like to call a “retrospective significance” for repetitive DNA—that is, they justify its existence by discussing the benefits it may confer upon distant evolutionary futures.

  Suppose all working genes could only exist in one copy that coded for an essential protein. How then could substantial evolutionary change ever occur? What will supply the essential protein while evolution monkeys about with the only coding sequence that produces it? But if a gene can repeat itself, then one copy might continue to code for the essential protein, leaving the other free to change. Thus, potential flexibility for evolutionary change has often been cited as the primary significance of repetitive DNA.

  I have no quarrel with the idea that redundancy may supply the flexibility that evolution requires for initiating major changes. Susumu Ohno, who first popularized this idea in 1970 in a brilliant book (Evolution by Gene Duplication), argued that, without redundancy “from a bacterium only numerous forms of bacteria would have emerged.” Duplication supplies the raw material of major evolutionary change: “The creation of a new gene from a redundant copy of an old gene is the most important role that gene duplication played in evolution.”

  But think about it for a moment. The argument is sound and may represent, in fact, the major effect of gene duplication for evolution. Yet unless our usual ideas about causality are running in the wrong direction, this flexibility simply cannot be the adaptive explanation for why repetitive DNA exists. Selection works for the moment. It cannot sense what may be of use ten million years hence in a distant descendant. The duplicated gene may make future evolutionary change possible, but selection cannot preserve it unless it confers an “immediate significance.” Future utility is an important consideration in evolution, but it cannot be the explanation for current preservation. Future utilities can only be the fortuitous effects of other direct reasons for immediate favor.

  (The confusion of current utility with reasons for past historical origin is a logical trap that has plagued evolutionary thinking from the start—see essay 11. Feathers work beautifully in flight, but the ancestors of birds must have evolved them for another reason—probably for thermoregulation—since a few feathers on the arm of a small running reptile will not induce takeoff. Our brains enlarged for a set of complex reasons, but surely not so that some of us could write essays about it. Interested readers may wish to consult a technical article that Elisabeth Vrba and I have written about this subject—see bibliography. We wish to restrict the term adaptation only to those structures that evolved for their current utility; those useful structures that arose for other reasons or for no conventional reason at all, and were then fortuitously available for other usages, we call exaptations. New and important genes that evolved from a repeated copy of an ancestral gene are partial exaptations, for their new usage cannot be the reason for the original duplication.)

  The second set of adaptive arguments is legitimate in proposing an immediate selective benefit for repeated DNA. If genes move about and insert themselves on different chromosomes, for example, they may occasionally link up with other segments of DNA to form advantageous new combinations. More importantly, much DNA, while not coding for protein itself, may play a role in regulating the DNA that does. This regulatory DNA may turn other genes on and off and may determine the sequence and location of expression for the genes that do code for proteins. If repetitive DNA performs these regulatory functions, then its dispersal throughout the genome can have profound immediate effects. Inserted into a new chromosome, it may turn adjacent genes on and off in new ways and sequences. It may, for example, bring together the products of two genes that had never been in proximity. This new combination may benefit an organism (see the classic article of Roy Britten and Eric Davidson, 1971).

  Yet, for all these efforts, the nagging suspicion remains that these adaptive explanations cannot account for all repetitive DNA. There is simply too much of it, too randomly dispersed, too apparently nonsensical in its construction, to argue that each item perseveres because natural selection has favored it in a regulatory role. The selfish DNA hypothesis proposes a fundamentally different explanation for much of this repetition. It is radical in that literal sense of getting to the roots, for it demands that we reassess some basic and usually unquestioned assumptions of evolutionary argument—what Orgel and Crick meant when they spoke of facts “so odd that only a somewhat unconventional idea is likely to explain them.”

  The argument is simplicity itself once you establish the frame of mind to permit it: if repetitive DNA is transposable, then why do we need an adaptive explanation for it at all (at least in conventional terms of benefits to bodies)? It may simply spread of its own accord from chromosome to chromosome, making more copies of itself while other “sedentary” genes cannot. These extra copies may persist, not because they confer advantages upon bodies, but for precisely the opposite reason—because bodies do not notice them. If they have no effect upon bodies, if they are (in this sense) “junk,” then what is to stop their spread? They are merely playing Darwin’s game, but at the “wrong” level. We usually think of natural selection as a struggle among bodies to leave more surviving offspring. Here certain genes have found a way, through transposability, or “jumping,” to leave more copies of themselves within a body. Is any other explanation required? Orgel and Crick’s title reflects this reversed perspective: “Selfish DNA: The Ultimate Parasite.”

  I can now almost hear the disappointment and anger of some readers: “That bastard Gould. He led us along for pages, and now he gives an explanation that is no explanation at all. It just plain happens, and that’s all there is to it. Is this a joke or a counsel of despair?” I beg to differ from this not entirely hypothetical adversary (a composite constructed from several real responses I have received to verbal descriptions of the selfish DNA hypothesis). The explanation seems hokey only in the context of adherence to traditional views that all important features must be adaptations and that bodies are the agent of Darwinian processes. The radical content of selfish DNA is not the explanation itself, but the reformulated perspective that must be assimilated before the explanation confers any satisfaction.

  If bodies are the only “individuals” that count in evolution, then selfish DNA is unsatisfying because it does nothing for bodies and can only be seen as random with respect to bodies. But why should bodies occupy such a central and privileged position in evolutionary theory? To be sure, selection can only work on discrete individuals with inherited continuity from ancestor to descendant. But are bodies the only kind of legitimate individuals in biology? Might there not be a hierarchy of individuals, with legitimate categories both above and below bodies: genes below, species above? (I confe
ss to what evolutionists call a “preadaptation” for favorable response to the selfish DNA hypothesis. I have long argued that species must be viewed as true evolutionary units and that macroevolutionary trends are often powered by a “species selection” that is analogous to, but not identical with, natural selection acting upon bodies.) Selfish DNA may do nothing for bodies, but bodies are the wrong level of analysis. From a gene’s point of view, transposable elements have developed a great Darwinian innovation: they have found a way to make more surviving copies of themselves (by repetition and transposition), and this, in itself, is the evolutionary summum bonum. If bodies don’t notice this repetition, and therefore cannot suppress it by dying or failing to reproduce, then so much the better for repeating genes.

  In this sense, selfish DNA is about the worst possible name for the phenomenon, for it records the very prejudice that the new structure of explanation should be combating: an exclusive focus on bodies as evolutionary agents. When we call repetitive DNA “selfish,” we imply that it is acting for itself when it should be doing something else, namely, helping bodies in their evolutionary struggle. Likewise, we should not refer to repetitive DNA as “nonadaptive,” for although it may not be helping bodies, it is acting as its own Darwinian agent. I can’t think of a much better name in a language replete with anthropocentric terms, but how about “self-centered DNA”—without the opprobrious overtones that “selfish” inevitably contains.

  Another argument against the use of selfish DNA lies in its historical source: Richard Dawkins’s book The Selfish Gene (1976). Dawkins argued that bodies are the wrong level of evolutionary analysis and that all evolution is nothing but a struggle among genes. Bodies are merely temporary containers for their selfish genes. Superficially, this looks like selfish DNA writ larger, hence Orgel and Crick’s decision to borrow the term. In fact, the theories of selfish genes and selfish DNA could not be more different in the structures of explanation that nurture them.

  Dawkins writes as a strict Darwinian, committed to the idea that all features must be interpreted as adaptations and that all of evolution is a struggle for existence among individuals at the lowest level. He merely decided that Darwinians weren’t radical enough in reducing such higher-level reveries as “the good of the species” or “the harmony of nature” to the unrestrained struggle of organisms. The struggling items are one level lower—genes rather than bodies—and the Darwinian program of reduction can go even further than modern supporters had dared to hope.

  Selfish DNA, on the other hand, gains its rationale from the antireductionistic belief that evolution works on a hierarchy of legitimate levels that cannot be collapsed to the first rung of the scale. Dawkins’s selfish genes increase in frequency because they have effects upon bodies, aiding them in their struggle for existence. Selfish DNA increases in frequency for precisely the opposite reason—because it initially has no effect on bodies and therefore is not suppressed at this legitimate higher level. Dawkins’s theory is an unconventional proposal to explain ordinary adaptation of bodies (see my critique in The Panda’s Thumb). Selfish DNA survives only because it makes no difference to bodies.

  But if middle-repetitive DNA is self-centered, why does it only exist in hundreds of copies within genomes? If it can spread by transposition while other genes cannot, why does it not generate millions and billions of copies, eventually crowding everything else out? What stops it? Why is it behaving as an “intelligent” parasite (enough copies to be comfortable and powerful, but not enough to destroy the host and itself), rather than as a voracious cancer?

  The potential answer to this question, proposed by both sets of authors, illustrates another interesting point about the hierarchical mode of thinking that underlies the theory of self-centered DNA. In hierarchical models, levels are not independent, walled off by impenetrable boundaries from those above and below. Levels leak and interact. Arthur Koestler, whom I do not usually praise but whose commitment to hierarchy I find admirable, chose as his metaphor for hierarchy the double-faced god Janus, standing at one level but looking for connections in both directions.

  Consider different forms of selection working at levels of gene, body, and species. A transposon enters a genetic system and begins to amplify itself by replication and movement. In the process of selection among genes, it is increasing by an analog of what we would call “differential birth” in natural selection among bodies. Its increase initially produces no interaction with the level of natural selection upon bodies, and nothing suppresses its intrinsic drive to manufacture more copies.

  But eventually, if its increase continues unabated, bodies must begin to notice. There is an energetic cost attached to the replication, generation after generation, of hundreds or thousands of copies of DNA sequences that do nothing for the bodies investing that energy. Bodies may not notice a few copies, but vast numbers must eventually produce a disadvantage at the good old Darwinian level of natural selection among bodies. At this point, a further increase in self-centered DNA will be suppressed because bodies carrying too many copies will suffer in natural selection, taking all their copies with them when they die or fail to reproduce. The usual level of tens to hundreds of copies may well represent a balance between inexorable increase at the level of selection among genes and eventual suppression at the next level of selection among bodies. Levels are connected by complex ties of feedback. My plea for a recognition of selection at levels other than bodies is not a negation of Darwinian theory but an attempt to enrich it.

  The arguments will continue for a long time. One group of scientists notes the similarity in arrangement within chromosomes of repetitive sequences in two creatures as evolutionarily distant as the toad Xenopus laevis and the sea urchin Strongylocentrotus purpuratus. This similarity refutes self-centered DNA and points to common function, since wandering transposons, beholden only to their own level, should disperse more randomly among chromosomes. Others point out that an important transposable element in yeast and another in the fruit fly Drosophila melanogaster are represented in different strains of the same species by about the same number of copies, but in very different positions among chromosomes. Do the different positions represent self-centered amplification and the similarity in numbers reflect suppression at the higher level of selection upon bodies?

  As with all interesting questions in natural history, the solution requires an inquiry about relative frequency, not an absolute yes or no. The logic of self-centered DNA seems sound. The question remains: how important is it? How much repetitive DNA is self-centered DNA? If the answer is “way less than one percent” because conventional selection on bodies almost always overwhelms selection among genes, then self-centered DNA is one more good and plausible idea scorned by nature. If the answer is “lots of it,” then we will need a fully articulated hierarchical theory of evolution. My own inclinations are, obviously, for hierarchy. Cartesian reductionism has been the source of science’s triumph for 300 years; but I suspect that we have reached its limits in several areas.

  We have legitimate, idiosyncratic reasons for continuing our linguistic habit of identifying “individuals” with bodies, and for granting a primacy to bodies among the objects of nature. I can’t, for example, imagine any acceptable politics that does not focus upon the primacy of individual bodies—and we weep for the inhumanity of those that did not, but flourished for a time nonetheless. Nature, however, acknowledges many kinds of individuals, both great and small.

  14 | Hen’s Teeth and Horse’s Toes

  VANITY LICENSE PLATES are the latest expression of an old conviction that distinctive conveyances reflect status or, at least, compel notice. We can build our modern machines to order, but nature has narrower limits. Horses of unusual size or color commanded great favor, but Julius Caesar ventured beyond the mere accentuation of normality in choosing his favorite mount. The historian Suetonius writes that Caesar

  used to ride a remarkable horse, which had feet that were almost human, the hoofs being
cleft like toes. It was born in his own stables, and as the soothsayers declared that it showed its owner would be lord of the world, he reared it with great care, and was the first to mount it; it would allow no other rider.

  Normal horses represent the limit of evolutionary trends for the reduction of toes. Ancestral Hyracotherium (popularly, but incorrectly, known as Eohippus) had four toes in front and three in back, while some earlier forebear undoubtedly possessed the original mammalian complement of five on each foot. Modern horses retain but a single toe, the third of an original five. They also develop vestiges of the old second and fourth toes as short splints of bone, mounted high and inconspicuously above the hoof.

  Marsh’s 1892 figures of polydactyl horses. Left, a normal horse. Note the splint remnants of side toes labeled II and IV. Middle: polydactyly by duplication. The side splints are still present and the extra toe is a duplicated third digit. Right: polydactyly by atavism. The extra toe is an enlarged side splint.