by Pross, Addy
Fig. 6. Two-phase (chemical and biological) transformation of non-life into complex life.
Let us then begin our discussion with the traditional view for the transformation of non-life into complex life. This can be represented as a two-stage process as illustrated in Fig. 6.
The first stage, the so-called chemical phase (termed abiogenesis, meaning the process by which life emerged from non-life) is where the never-ending debate and controversy lie. In the context of Fig. 6, a simple life form would mean that the system would possess what many would argue would be the most significant characteristic of living things—the ability to replicate and evolve in a self-sustained way. Indeed, having reached that critical point, the system would be considered biological in nature and its subsequent transformation into more complex life—single-celled eukaryotes and multicellular organisms—would have been governed by that momentous and earth-shattering theory that was proposed just 150 years ago, Darwinian evolution. So the conventional wisdom is that we are facing a two-stage process whose first stage is highly contentious and uncertain, while the second stage, in scientific circles at least, is in broad terms now unshakeable.
Let me now drop the bombshell, at least for many in the field. The so-called two-stage process is not two-stage at all. It is really just one single continuous process. If true that statement has quite profound consequences. First it must mean that hidden within Darwin’s theory of evolution—biological in formulation and application—a more fundamental, broader principle is at work, which must necessarily incorporate prebiotic systems, which by definition would be classified as non-living. In this chapter, I will attempt to justify the one-process assumption and explore some of its implications.
Why has the process indicated in Fig. 6 been considered a two-phase process until now? To put it bluntly—because of our ignorance. Knowing the mechanism of one phase and not knowing the mechanism of the other is a clear point of division and leads quite naturally to the separate classification. However, ignorance is not a useful basis for classification, so let me now try to justify the assertion that abiogenesis and biological evolution are in fact one single continuous process. And I don’t mean that in a trivial sense. It is obvious that if some prebiotic entity complexified into a simple living thing by some unknown mechanism, and then proceeded to evolve and diversify into the extraordinary range of living species, then whatever that early prebiotic process was, it could be thought of as continuous with the biological phase, at least in a temporal sense. But I intend the statement in a non-trivial sense—that the chemical process that led to the simple living creature and the biological process that subsequently carried on from there are one single process in a chemical sense. That is in fact exactly what recent studies in systems chemistry have been telling us. Let us review the empirical evidence.
In chapter 4, I described the molecular replication reaction of an RNA molecule carried out by Sol Spiegelman in the 1960s. We saw that molecular replication is a chemical reality and can take place in a test tube, and not just in the highly regulated and specific environment of a cell. Recall, however, that Spiegelman also discovered that the population of replicating RNA molecules can evolve.27 Over time the initially long chain RNA molecule evolved into shorter RNA chains. Shorter RNA molecules which replicated faster, out-replicated the longer ones, driving those longer ones to extinction. So what is termed natural selection within the biological world is also found to operate in the chemical world. The conclusion is highly significant. The causal sequence: replication—mutation—selection—evolution, normally associated with the biological world, in fact the sine qua non of biology, is also clearly evident at the chemical level. That landmark work was carried out over forty years ago and since then the phenomenon of molecular evolution—evolutionary-like behaviour at the molecular level—has been observed by a growing number of researchers. Accordingly, the generality of evolutionary processes within replicating entities at the molecular level is now well documented and experimentally uncontroversial.
But the chemistry-biology nexus runs much deeper. Ecology is an established branch of biology and would seem to be quite unrelated to chemistry. However, as Gerald Joyce, the remarkable Scripps biochemist, reported in 2009, there is an intimate connection between the two.53 A key ecological principle, termed the competitive exclusion principle, states: ‘Complete competitors cannot exist’ or, expressed in its positive form: ‘Ecological differentiation is the necessary condition for coexistence’.54 What that principle teaches us is that two non-interbreeding species that occupy the same ecological niche (which just means that the two species compete for the same resources) cannot coexist—the one that is better adapted to that niche (i.e., is fitter), will drive the other to extinction. Of course, if the two species feed off different resources then coexistence is possible. This basic ecological principle is classically illustrated by Darwin’s finches—one of the best-known examples of evolutionary theory. On the Galapagos islands, where Darwin visited in 1835, one can find a variety of finches that differ in the size and shape of their beaks. These different finch varieties, all of which derive from a common ancestor, evolved over time so as to exploit available resources more effectively. In doing so one type of finch—ground finches—evolved strong beaks which are effective for cracking nuts and seeds, while another type—tree finches—evolved sharp pointed beaks which are adapted for eating insects. The point is that these distinct varieties of finch can coexist because each is adapted to feed off a different resource, and in that sense provide a good example of the competitive exclusion principle.
But here is where the chemistry-biology connection comes in. Gerald Joyce discovered that this quintessentially biological principle also operates in chemistry.53 Joyce found that when two different RNA molecules, let’s call them RNA-1 and RNA-2, were allowed to replicate and evolve in the presence of some essential substrate they were unable to coexist. RNA-1 turned out to be the more effective replicator with that substrate, and as a consequence it drove RNA-2 to extinction. If a different substrate was employed, one that RNA-2 was able to exploit more effectively, then the result was reversed. Now it was RNA-1 that was driven to extinction, as RNA-2 was the more effective replicator in the presence of that other substrate. Those chemical results are precisely in line with the predictions of the biological competitive exclusion principle. Since both replicators relied on the presence of a particular substrate in order to replicate, the two molecules were unable to coexist—the faster (fitter) replicator drove the slower one to extinction.
But a more interesting and quite remarkable result was to follow: when the two RNA molecules were allowed to replicate and evolve in the presence of not one, but five different substrates, the two RNAs were able to coexist, but in an unexpected way. Initially the two RNA molecules utilized all five substrates in varying degrees in order to replicate. After all, all five were present and therefore all five could be utilized to some extent. But here is the punch line: over time each RNA molecule evolved so as to optimize its replicative ability with respect to different substrates. RNA-1 evolved so as to optimize its replicative ability with just one of the five substrates, while RNA-2 evolved so as to optimize its replicative ability with another of those five substrates. As a result, the two RNAs were now able to coexist.
In this beautifully designed experiment, which explored the characteristics of competing molecular replicators, the two RNA molecules were found to mimic the behaviour of Darwin’s finches precisely! Each molecule evolved to exploit a particular substrate efficiently, just as Darwin’s finches had evolved beak size and shape to suit the nature of the resource. That spectacular result, in which molecular replicators mimic biological ones (actually vice versa—molecular replicators preceded the biological ones), speaks loud and clear for a strong chemical-biological connection. Darwin’s finches are merely doing what certain molecules started doing billions of years ago.
Finally, let me show that complexification of the special
kind normally found only in biological systems can also be discerned at the chemical level, and so provides yet another link between chemical and biological replication processes. We have already discussed the fact that complexity is the very essence of biology. In fact, over an evolutionary time frame it is quite evident that complexity has continually increased from relatively simple systems to more complex ones. The earliest life forms that emerged, perhaps 4 billion years ago, were simple cells, prokaryotes (meaning that the cells lack a nucleus and other organelles). But after a further 2 billion years of evolution, eukaryotic cells emerged, in which membrane-bound organelles, including the cell nucleus, can be found. And some 600 million years ago another evolutionary transition involving further complexification took place, the one in which multicell organisms—plants and animals—appeared.55 The evidence on this score is therefore unambiguous. Over the evolutionary time frame there has been a clear tendency for complexity to increase (though of course only among a small subsection of life, the multicellular eukaryotes; the vast majority of life, bacteria and archaeans, have remained happily simple). So within what we have labelled as the biological phase of Fig. 6, there is unambiguous evidence for a process of increasing complexity.
What can we say about the chemical phase of Fig. 6? In historical detail, almost nothing at all. But the essence of the transformation is quite clear. A molecular system, which we would characterize as non-living and relatively simple, somehow became transformed into a highly complex living cell, meaning the process involved was one of increasing complexity. As we have already pointed out, even the simplest living thing is highly complex. In other words, both chemical and biological phases of Fig. 6 involved a process of continual complexification. But how can this process of apparent complexification be understood at the chemical level?
As we have discussed in some detail in chapter 5, we are lacking any direct information regarding that early prebiotic period. However there is one thing we can state with high assurance regarding that early period. It is that the laws that govern chemical behaviour have not changed over the past several billion years, and that means that studying the right kind of chemistry today can inform us about what might have happened billions of years ago. And the right kind of chemistry is systems chemistry, the chemical reactions of replicating molecules and the networks they create.29,56 Such study may provide us with insight into the kinds of reactions that prebiotic replicators might have undertaken, amongst them that early process of complexification.
What have we then learnt regarding simple chemical replicators? First, getting single molecules to self-replicate is inherently difficult. In fact the difficulty in getting so-called replicating molecules to replicate when no biological materials are added to ‘help’ things move along, has been viewed as one of the stronger arguments against a replication-first scenario for the emergence of life. But let us return to some recent results from the Joyce lab as they are illuminating. Despite the difficulties inherent in getting single molecules to replicate, Gerald Joyce was able to come up with an RNA molecule that was able to make copies of itself without enzymatic assistance. In that particular reaction, a replicating RNA molecule, let’s call it T, itself composed of two RNA segments, A and B, underwent a replication reaction by the template mechanism (described in detail in chapter 4). The RNA molecule, T, acting as a template, induced fragment entities, A and B, which were floating about freely, to temporarily bind to itself and then link up, thereby creating a new molecule of T. The overall result, a single T molecule was able to make copies of itself by inducing its two component parts A and B, freely available in the solution, to connect up.57
Even though that replication reaction was possible, it was frustratingly inefficient. First, it was slow—it required seventeen hours for an initial sample of RNA to double in quantity. But slowness wasn’t the only problem. After all what is seventeen hours when compared to a billion-year time frame? An additional problem was that the replication reaction only proceeded for two replication rounds before grinding to a halt (due to certain side reactions), so it was not possible to continue the reaction, even when feedstock for further replication reactions (i.e., more A and B) was provided. But now to the interesting finding. When Joyce switched from a single replicating RNA molecule to a two-molecule system composed of two discrete RNA molecules that had been obtained in a careful selection process, then replication proceeded rapidly—the initial sample doubled in quantity in just one hour—and replication could be sustained indefinitely, provided the building blocks were available. How come? Why the difference?
Let’s start by stating what wasn’t happening. In the two-molecule RNA system each molecule was not making copies of itself. Rather, one RNA molecule was inducing the formation of the other, while the other molecule was inducing the formation of the first. In chemistry we call that cross-catalysis—each RNA molecule was catalysing the formation of the other. So the more complex system is self-replicating, but in a more complex way—each component of the system isn’t replicating individually, but the system as a whole is self-replicating. That distinction is important because holistic replication is the norm in biology; that’s what cells do when they replicate—the system as a whole makes copies of itself, as opposed to each individual component within the cell copying itself. So what is the significance of this result? Simply this: what one simple replicating entity could only do inefficiently, a more complex one was able to do more efficiently.
This chemical equivalent of ‘I’ll scratch your back, if you’ll scratch mine’ goes beyond the tit-for-tat exchange of favours, which is useful in itself. The deeper meaning is that what I cannot do well on my own, I can do more effectively in a cooperative way. Cooperation is win-win. No wonder cooperation is endemic in the biological world—biologists call it symbiosis. You see it wherever you look. So what Gerald Joyce discovered in those two RNA molecules was profound. Yet another piece of evidence that demonstrates how chemistry and biology are intimately connected. A process of molecular complexification has led to an enhanced replicative capability.
Let us take another look at Fig. 6 because it now takes on a new significance. Our discussion above has indicated that complexification facilitates both the molecular replication phase and the biological replication phase. In fact, the entire process when viewed over an evolutionary time frame is seen to be one of complexification. The main difference between the two phases is that the first phase, the chemical phase, is the low-complexity phase, while the second phase, the so-called biological phase is the high-complexity phase, all taking place within the context of replicating entities. The conclusion seems clear: complexification, primarily through network establishment, appears to be the mechanism for the transformation of simpler chemical replicators into more complex biological ones. In fact the recognition that complexification is a key process in evolution leads us to a surprising conclusion, namely, that the causal sequence that leads to evolution needs to be modified. Evolution in biology is normally associated with the causal sequence: replication, mutation, selection, evolution. But we now see that an important step in that sequence has been overlooked. The missing step is complexification. The sequence should read: replication, mutation, complexification, selection, evolution and this is true for both the chemical and biological phases.
Some words of clarification are now appropriate. The previous discussion might suggest that the evolutionary process is based solely on complexification and this is clearly not the case. It is well established that in particular instances evolution follows a process of simplification. Biology in particular is replete with such cases—for example, cave-dwelling animals such as crickets and cavefish that lose their eyesight as they adapt to life in the dark. But, remarkably, in chemical systems precisely the same phenomenon of simplification can also be observed. Recall Spiegelman’s experiments on molecular evolution in which replicating RNA chains shortened because the shorter chains replicated faster.27 That classic study provides a chemical
example of simplification. Just as cavefish lose their ability to see in dark caves, RNA chains (extracted by Spiegelman from the Qβ virus) discard those parts of the viral genome that prove redundant in the artificial resource-rich test-tube environment. The very existence of a process of simplification in both biological and chemical evolution serves to further strengthen the chemistry-biology connection and provides yet an added piece of evidence supporting the unity of the evolutionary process of Fig. 6. Returning however to the present theme, regardless of those well-documented instances of simplification, it is clear that complexification is the underlying tendency in evolution, in both the chemical and biological worlds.
