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Sketches for a Mineral Genetic Material A. Graham Cairns-Smith1 I will argue that the driving force for the transition from geochemistry to biochemistry was natural selection operating, in its earliest stages, on inorganic materials. The most critical requirement for truly primitive evolvable systems is truly primitive genetic materials. These should have the kind of permutable structure that can hold information, and they should be able to replicate this information—very accurately for the most part. They should be like DNA in these respects. But, unlike DNA, they must do it all without any pre-evolved systems. Mixed-layer and polytypic materials will be featured in attempts to sketch what we should be looking for. KEYWORDS: origin of life, natural selection, takeover, mixed-layer, polytype, clays INTRODUCTION For an organic chemist, it is humbling to think about bacteria because these supposedly simplest of organisms are amazingly good at doing organic chemistry. They can put together molecules requiring many steps in their making. Difficult, often huge molecules such as proteins are churned out, thousands of different kinds of them, each a characteristic constellation of some thousands of atoms and with every atom connected up just so. Such competence could only be a product of evolution through natural selection. Yet for today’s organisms it is a precondition too—for to take part in evolution, in today’s way, a high organic-chemical competence is absolutely required. This is the Fix we find ourselves in when we try to think about the origin of it all. It is a Fix that arises, I think, from the very nature of organic molecules, together with a preconception that because they are so important now this must have been so from the very beginning. The Great Virtue and the Great Snag about Organic Molecules as the Basis of Life Organic molecules are ideal for highly evolved forms of life (such as bacteria) if only because of the enormous number of different molecules that can be made from a construction kit of atoms composed mainly of C, H, O, N, P, and S. Extrapolating from results of Henze and Blair (1931), I concluded (1971, p. 2) that there are more possible ways to connect 200 carbon atoms with 402 hydrogen atoms than the number of electrons in the Universe, which according to a famous estimate is about 1079 (Eddington 1935, p. 221). And most protein molecules contain many more atoms than 602, and more kinds of atoms too. The Great Virtue of such richness in the world of possible organic molecules is that it allows the kind of complex 1 Department of Chemistry, University of Glasgow, Glasgow, G12 8QQ, Scotland E-mail: [email protected] ELEMENTS, VOL. 1, PP. 157-161 molecular engineering found in all the organisms around us now. The Great Snag is that with so many possibilities there are so very many ways to go wrong—and end up being a speck of dark intractable tar instead of an exquisite piece of sub-nano-engineering. To make particular organic molecules, detailed control is needed all the way. In today’s organisms a crucial part of this control is provided by enzymes, which bring about virtually every biochemical reaction taking place. How Enzymes Work An enzyme is a highly tuned molecular machine. It selects and binds one or more particular molecule(s)—its “substrate”—from a diverse crowd of molecules in its surroundings. In the very act of binding, the enzyme exerts precise forces on its substrate to transform it in a particular way. An enzyme is mainly or entirely made of protein. It consists of one or more chains of (usually) 20 kinds of amino acids, covalently linked together in a definite sequence. A typical chain might have some two or three hundred amino acids in it, so that its unique sequence is one of an astronomical number of alternatives (way beyond “the number of electrons in the Universe”). Often, such a protein chain folds up in a complicated way that depends in detail on its unique sequence. An enzyme protein may fold so as to create, somewhere on its surface, a specific groove or pit that is geometrically and electronically complementary to the molecule or molecules on which it acts. Enzyme and substrate fit together, and the fit becomes even better when the substrate is distorted in ways that lead to the required reaction. Such a set-up is indeed ideal for manipulation by Nature’s engineer, natural selection. This is because the active site of an enzyme—its critical “groove”—can be tuned by natural selection. This can happen through occasional arbitrary changes to a protein sequence arising from mutations in the genetic material DNA. Such changes in or near the groove would tend to make coarse adjustments to its shape and chemical properties. Changes a bit farther away will likely have smaller effects: perhaps moving components of the groove by fractions of an angstrom, for fine tuning. Similar considerations apply to other proteins. Yes, this whole set-up is ideal for participation in evolution in the way we now see it. But it is far from anything that might have “just happened” as part of a primitive organic geochemistry. Manifestly, the situation that now allows the evolution of organic-chemical competence must itself have evolved. How did that happen? Our Fix has worsened with 157 J UNE 2005 our increased understanding of the necessary complexities of the biochemical machinery. We need to think about an earlier phase of natural selection that did not in the first place depend on high organic-chemical competence, but could evolve to produce it. Is this feasible? I think it is, but only if we abandon the idea that organic molecules were always the stars in the play of evolution, as they are today. Even the smallish molecules, amino acids, and so on, owe their present significance to being parts of incredibly high-tech machinery. What we are looking for are low-tech beginners at evolution, and it is here that inorganic geochemistry is more likely to hold the keys. SKETCHES What are the minimal requirements for any system to be subject to natural selection? The most basic is heredity, illustrated in the well-known feature of living things that they reproduce and pass on characteristics to offspring. More strictly, what is passed on between generations is not a set of characteristics as such (a phenotype), but genetic information, which is the other, “invisible” part of an organism. This is the information about how to make and maintain a phenotype. It can be thought of as a set of controlling patterns—recipes of some sort (a genotype). The first sketch, after Maynard Smith (1993), illustrates the relationship between genotype and phenotype for the case of (say) micro-organisms reproducing by cell division: ä P ä P ä P ä P′ ä P′ à G à G à G à G′ à G′ à MUTATION! Phenotypes are not copies of previous phenotypes. On the other hand, genotypes are usually accurate copies of previous genotypes—there is an unbroken succession of arrows between the Gs. In addition there is the occasional mutation, which can be thought of as a “misprint” in the genetic information. This will often produce a change in the phenotype which, if not too damaging, will be inherited from then on. Why Natural Selection is so Powerful Mutations are effectively random events. But this is not to say that because evolution depends on them, evolution must be “just a matter of chance”. What makes natural selection so much more effective than “pure chance” is that it can proceed small-step-by-small-step—because partial success is, in an important sense, remembered. Thus further explorations can be made by randomly modifying what was already successful—in the crucial self-demonstrating sense of being more prevalent (surviving better, reproducing faster, spreading more widely, and so on) and so more likely to be the basis of future random modifications. The critical feature of the above diagram is the long-term memory, maintained through the accurate copying of genetic information. The next sketch, a modified version of the previous one, emphasises where there had to be high competence from the start (in the copying of the genetic information) and where competence could have evolved later (in the production of phenotypes). ä P ä P ä P ä P′ ä P′ è G è G è G è G′′ è G′′ è MUTATION! ELEMENTS A phenotype can be seen in the most general terms as a set of physico-chemical consequences of genetic patterns, consequences that affect the chances of the propagation of these patterns. The consequences do not have to be anything very wonderful. To have a fair chance of catching on, a phenotypic effect, even today, needs only to confer some advantage even if small (Dawkins 1986). Overcoming the Great Snag Suppose the first genetic material was inorganic. We might think of a microcrystalline mineral that has some replicable pattern superimposed on its crystal structure, a pattern that is inherited as a matter of course by newly crystallising material. Now suppose that a consequence of such a pattern is that it affects the morphology of the crystals holding it, which in turn helps their survival and propagation. FIGURE 1A is a cartoon example of how this might happen and FIGURE 1B a conceivable case in point. Figure 1a illustrates the point that a first phenotype might simply be a property of the genetic material itself (Spiegelman 1970; Orgel 1979; Eigen 1983; Joyce 2002). But we can think too about simple indirect phenotypic effects, involving nongenetic materials. Suppose that the replicable pattern of a genetic crystal affects the population of ions and other molecules that accumulate on or near its surfaces, altering the local pH, perhaps, which in turn happens to favour the growth of the genetic crystals. Or suppose that some replicable pattern has the effect of organising, just a little bit, some mix of organic molecules in the surroundings, through adsorptive and catalytic interactions. Adsorption and catalysis are common-enough effects of inorganic surfaces, and “just a little bit” might be enough. For example the crystallising materials might be clay minerals and the organising effect might be to increase slightly the local population of di- and/or tri-carboxylic acids, since these can act as catalysts for clay synthesis by chelating and mobilising insoluble ions, especially Al(III) (Siffert 1986). Small di- and tri-carboxylic acids have a central place in our biochemistry, and it has been suggested from the structure of our present metabolic pathways that such acids were perhaps the very first organic molecules in our evolutionary history (Hartman 1975; Cairns-Smith 1982, 1985, 2003). But my main point here is that it is easy to imagine organic molecules as primitive phenotypic components where even rather disorganised mixtures might be effective. The great trouble with the idea of organic molecules in an early genetic role is illustrated by DNA, where clean and maintained supplies of DNA monomers (nucleotides) are the absolute minimum requirements for its replication, and nucleotides (whether for DNA or RNA) are particularly tricky molecules to make (Cairns-Smith 1982, pp 56-59; Shapiro 1988, 1995; Orgel 2004). AN APPROACH TO G1 To be simple, and yet have a reasonably high information capacity, a first genetic material should be made from a limited number of units that can be arranged in a very large number of ways. DNA is like this. It holds its information in the form of stacking sequences of tiny flat plates—base pairs—held in place by an entwining pair of sugar–phosphate strings. There are two kinds of base pairs, and each can be oriented in the stack in one of two ways. The Power of Permutation To get an idea of the amount of information that a structure like this can hold, consider this: a particular stack of 150 DNA base pairs is one arrangement out of about 1090 possible arrangements. And to get a rough idea of just how 158 J UNE 2005 A Different Way of Replicating A Coming to the actual process of replication, this could be very much simpler with “layer crystal genes” (as I will call them) than with the necessarily highly orchestrated procedures of DNA replication, as I have discussed elsewhere (1982). FIGURE 2 is a formal sketch of how such a crystal gene might replicate a stacking sequence. The first requirement for such a mechanism is that units in the surrounding fluid should add only to the edges of the layer stacks, and in such a way as not to disturb the sequence, indeed to copy the sequence (Cairns-Smith 1988). B A mineral genetic material might hold information in the form of a particular complex stacking sequence of layers and replicate it through an appropriate alternation of growth and cleavage. FIGURE 2 A. In this cartoon a ground water solution of silicic acid and metal cations is moving through a porous medium such as sandstone, and minerals such as clays or zeolites are crystallising from the solution. Crystals with chunky morphologies (A) would be likely to block the pores and cut off local nutrient supplies, while crystals that are too small or delicate (B) would tend to wash away. A good compromise would be to stick to the surrounding sand grains while not blocking the pores (C). FIGURE 1 B. This figure shows illite clay crystals from a marine sandstone, which are conceivably a product of a simple kind of natural selection favouring crystals that stick to the sand grains while not blocking the pores (see figure 1a). Such tapelike illites consist of small stacks of a few silicate layers. The inner layers are strongly negatively charged on both their top and bottom surfaces, like mica, and are held together firmly by (dry) potassium ions between them. However, the outer surfaces of the top and bottom layers in a stack have a lower charge (more like montmorillonite). These outer surfaces are hydrated and hold (hydrated) ions such as sodium and calcium (Nadeau et al. 1984). Micrograph reproduced from McHardy et al. (1982). far beyond the reaches of pure chance are all the forms of life now on Earth, consider the bacterium E. coli. It has 4.6 million base pairs in its genotype. (Humans have a few hundred times as many, about 3.3 billion.) What we seek is altogether more modest and certainly not DNA. There are however some inorganic materials, including some clay minerals, that are formally like DNA in one crucial respect: they consist of stacks of layers that are either of different kinds (mixed-layer materials) or of different orientations (polytypes). In several cases, the layers may be arranged in more or less arbitrary sequences. Such materials could in principle hold information. Furthermore, the conditions required for their synthesis— for example, ground waters containing silicic acid and metal cations—were most likely available on the primitive Earth, as they are now (Odin et al. 1986). ELEMENTS Indirect support for this kind of faithful sideways copying comes from a phenomenon sometimes seen in layer crystals where some complex random-looking block of layers is repeated several times, one on top of the other. Examples of this come from mixed-layer materials. Although formed at high temperatures, barium ferrites have provided some especially dramatic cases. For example, Kohn et al. (1971) found a 526 Å repeating sequence of 37 layers, while in another study McConnell et al. (1974) found an 841 Å sequence of 59 layers. Each of these groups remarked that limitations of their (different) electron microscope techniques may have prevented even longer repeating sequences from being found. Clay minerals frequently have mixed-layer structures and often show (more modest) sequence repeats (Reynolds 1986). There is a similar story with polytypes, e.g., silicon carbide (Verma and Krishna 1966) and micas (Baronnet 1980; Baronnet and Kang 1989). The classical explanation for such repeats (Frank 1951) is that the crystals would have grown through addition of units to edges that are exposed on the surface due to a deep screw dislocation. An alternative less tidy mechanism has been suggested more recently (FIG. 3) to explain the long repeats found in barium ferrites (Turner et al 1996). This “seaweed growth” mechanism also depends on faithful sideways addition of units. A similar mechanism might apply to other cases of long c-axis repeats. FIGURE 4 is a second sketch for an imagined mineral genetic material. The picture is supposed to be part of one flexible, branching, sprawling multi-layer (say, 10–100 layers thick) and which has the same stacking sequence everywhere, displayed on its many edges like a vertical bar code. The whole thing is somewhat like a plant reproducing vegetatively—as happens with clover for example. One clone may eventual- 159 J UNE 2005 And it is here, on the edge surfaces, that catalytic and adsorptive sites would be most directly influenced by sequence patterns. This might be possible—I am thinking of those misfitting strains where, in the middle of a complicated sequence, there might be, say, an adjacent pair of layers, A and B, which create a row of edge sites that depend very much on the chemical nature of A and B and how well they sit together. But these sites might depend also, if more subtly, on the layers above and below them— and so on, with the effects getting weaker with distance. Transmission of such “mechanical” effects through articulated silicate structures has been discussed by Megaw et al. (1962); see also Cairns-Smith (1982, p 223). This possibility, although speculative, is reminiscent of the evolutionary “fine tuning” of protein catalysis discussed earlier. Takeovers and the Evolution of the Means to Evolve A genetic takeover Cartoon sketch illustrating a possible mechanism for long repeat sequences quite often found in mixed-layer crystals. A seed crystal (top left) consists of a stack of layers with some arbitrary sequence. It grows by addition of units to its edges only (compare figure 2). The resulting more extensive plate is branched and flexible. It grows like seaweed so that “fronds” come to overlap and subsequently pile on top of each other producing thicker crystals in which the original arbitrary sequence in the seed is repeated several times (e.g., bottom right). The colour coding and numbering refer to different levels of the same stack of layers. FIGURE 3 FIGURE 5 illustrates how an evolutionary process could result in a radical change in genetic materials. No great leap would be needed, only a gradual process with intermediate stages in which evolving systems would use more than one genetic material. This diagram represents a series of snapshots on a time scale of perhaps hundreds to millions of years. It is the simplest form of a “genetic takeover”— between just two genetic materials. Formal representation of a radical genetic takeover. Here phenotypes are represented as boxes, which protect the genetic information and enable it to replicate more effectively. But they let in the possibility of a new kind of genetic material (red) based on materials that had not previously been available. After a period of collaboration the new system ousts the old. FIGURE 5 FIGURE 4 An artist’s impression of a primitive mineral gene that reproduces vegetatively (see figs 1b, 2, and 3b, and text). ly spread over a whole field (Harper 1982). A sprawling primitive gene like this could still evolve, if, for example, a branch were to develop a stacking fault. And its Phenotype? Morphology could be a phenotypic feature (compare fig. 1)— for example the thickness of the fronds, their style of branching, their width—in so far as such features could influence (say) accessibility of nutrient solutions or robustness to unfavourable conditions. Or perhaps undersaturated conditions would allow small pieces to break off more easily if the width of a frond tended to vary along its length. Particularly with mixed-layer structures (that is to say, structures made from chemically different layers lying on top of each other), there would be strains due to slight misfits that might tend to limit growth in certain directions or cause curling. Such strains might affect the amount and style of branching and hence the proportion of edges where the genetic information is displayed. Indeed this whole design with its flexible branching fronds increases the prevalence of edges. ELEMENTS There are analogies here with human technological advance where similar takeovers abound. The quill pen was not gradually transformed into the word processing computer through a graded succession of intermediate designs, but through an overlapping succession of takeovers using novel technologies, each made possible by the evolution of a whole surrounding technology. In more recent biological evolution too there have been takeovers. Gills did not evolve through intermediate designs into lungs—there was a gradual takeover through organisms (such as lungfish) that had both. I think that takeovers would have had a special place at the earliest stages of evolution. A series of genetic takeovers could have provided the main mechanism for the evolution of the means to evolve—that is to say the evolution of the genetic system itself. I also think that it was through an overlapping succession of takeovers that different schemes could have been tried out—simple ones to begin with, more complicated ones becoming possible later. A Genetic Staircase? All the free-living organisms on Earth that we know of have essentially the same highly integrated DNA-based system that provides, now, the means to evolve. The implication of this sameness is that all living creatures on Earth today, 160 J UNE 2005 from bacteria to barley to bishops, are (in some sense) descended from a single common ancestor that already had this system in full working order with its fundamental features fixed, that is to say no longer subject to evolution. Probably this arose from the kind of multiple interdependence of subsystems that is so typical of high-tech machinery in general (Cairns-Smith 1982, chapter 3). Surely there must have been a prolonged or intensive evolution through natural selection to have brought such machinery into existence. I would guess that this started piecemeal with perhaps one kind of mineral genetic material, followed by several based on different kinds of mixedlayer or polytype materials: symbioses of several primitive genetic materials with different evolved skills. FIGURE 6 is a cartoon of the sort of thing I am trying to imagine here. It is a kind of staircase showing roughly how lines of genetic succession might have been arranged. The staircase has all but collapsed now, but beginners like G1 should still be with us engaging in, at least, tiny temporary evolutionary processes. Perhaps these seem too trivial to be recognised for what they are. Hydrothermal systems might be the place to look. They are being increasingly invoked as sites for “the origin of life” (Holm 1992; Russell and Hall 1997), and they seem especially good places for the earliest stages of the kind of evolution we are trying to imagine. Layer silicates, for example, grow and dissolve relatively quickly at moderately high temperatures and pressures. Finally, returning to the main theme of this essay, whatever the detailed story was, there would not have been one fixed set of materials all the way because the most accessible and REFERENCES Baronnet A (1980) Polytypism in micas: a survey with emphasis on the crystal growth aspect. In: Kaldis E (ed) Current Topics in Materials Science, North Holland Publishing Company, Amsterdam, pp 447-548 Baronnet A, Kang ZC (1989) About the origin of mica polytypes. Phase Transitions 16/17: 477-493 Cairns-Smith AG (1971) The Life Puzzle. University of Toronto Press, Toronto Cairns-Smith AG (1982) Genetic Takeover and the Mineral Origins of Life. Cambridge University Press, Cambridge Cairns-Smith AG (1985) Seven Clues to the Origin of Life. Cambridge University Press, Cambridge, 154 pp Cairns-Smith AG (1988) The chemistry of materials for artificial Darwinian systems. International Reviews in Physical Chemistry 7: 209-250 Cairns-Smith G (2003) Fine-tuning in living systems: early evolution and the unity of biochemistry. International Journal of Astrobiology 2: 87-90 Dawkins R (1986) The Blind Watchmaker. Longman, Harlow, Essex, chapter 4 Eddington A (1935) New Pathways in Science. Cambridge University Press, Cambridge Eigen M (1983) Self-replication and molecular evolution. In: Bendall DS (ed) Evolution from Molecules to Men, Cambridge University Press, Cambridge, pp 105-130 Frank FC (1951) On the growth of carborundum: dislocations and polytypism. Philosophical Magazine 42: 1014-1021 Harper JL (1983) A Darwinian plant ecology. In: Bendall DS (ed) Evolution from Molecules to Men, Cambridge University Press, Cambridge, pp 323-345 ELEMENTS A genetic staircase. The idea here is that there were multiple overlapping genetic takeovers. First there was one genetic material. Then there were several doing different jobs. 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